How many times have we all jotted down a list to take with us to the supermarket? Even a simple vertical column of ordinary household items requires more than we realize. We scan areas of the house and pull from memory different food stuffs or supplies that need to be replenished or replaced: refrigerator (need milk, butter, juice); cabinets (we’re out of sandwich bags and sponges); canisters (need coffee and tea); laundry room (need detergent and bleach); dinner (….. good question). All this information requires a flow of memory, organization, and planning. Most of us do this part of the task spontaneously and routinely.

Now we need to create that list on paper. As automatic as it seems, writing simple words like “coffee,” “sandwich,” and “juice,” requires a call-up of a sequence of letters and shapes for each word—spelling--and an ability to manipulate the pen or pencil in order to encode the letters. During the physical act of jotting down a list, we control several muscle groups to keep the writing tool flowing in a direction—moving vertically, horizontally, and in a circular fashion (rotary movement). Fine motor coordination is key as we stimulate certain muscle groups, inhibit others, and balance, flex, and contract movements. We don’t punctuate the list, write it in a creative way, grab the attention of a reader, or develop a theme and add flourish and detail to our assertions. A list is just a list.

Now that you realize the abilities this simple column calls for, think of a child who has graphomotor problems so that he or she writes letters in a laborious, illegible manner; who has sequencing problems so that spelling is greatly below par; and who has memory challenges so that the missing items or ingredients aren’t summoned easily to mind (or kept in working memory long enough to write them down). A shopping list becomes a whole new order of accomplishment, demanding effort even at this rudimentary level.

There are no statistics, but it is estimated by some psychiatrists and neuropsychycologists who treat and test children with bipolar disorder, that at least half of these children have disorders of written expression. The numbers may even be higher.

The problem for some children is language-based (and may co-exist with dyslexia); for others it is a motor outflow difficulty; and for many children with bipolar disorder, the problem may be a severe difficulty in organizing thoughts, relinquishing original ideas and reformulating them; and marshaling the energy and attention to complete the task. Any one of these problems will make writing a demand that will most likely be resisted—very vehemently, and with increasing frustration and anger.

What Happens When a Child Has to Write

According to Hilary J. Luttinger, MA, clinical research director of the Department of Medicine at Elmhurst Hospital Center and Mount Sinai School of Medicine in New York:

Writing is a complex task requiring the mastery and integration of a number of subskills. The process of writing connects cognition, language, and motor skills. Some children have difficulty in one aspect of the process, such as producing legible handwriting or spelling (dysgraphia), while others have difficulty organizing and sequencing their ideas. Difficulties in one area can delay skill development in the other areas.

Another layer of writing must develop as a child moves into higher grades. Dr. Mel Levine, in A Mind At A Time, writes that a student must “respond productively to the call for excellent language skill, rich idea development, and the arrangement of ideas and facts in a logical manner.” “In some cases,” he adds, “that call goes unanswered.”

What are some of the reasons that call goes unanswered, especially for children with bipolar disorder?

In addition to a motor and sequencing difficulty, a child with bipolar disorder may also have difficulties with the mechanics of writing (periods, commas, and capitals may be very late to arrive in any written product), working memory, intention (let’s get it done), and sustained attention. In a hypomanic state, the thoughts may race and ideas pour out faster than the motor or organizational controls; conversely, in a depressed phase, there may be a slow-down of thought and a paucity of ideas.

We spoke with Dr. Dana Luck, a neuropsychologist in New York City and she explained:

Writing is a directed task and very different from speaking. Verbally, we can all mention thoughts, circle around them, move off in different directions, and hopefully get to the point somewhere along the way. Writing, however, is much slower and very much more precise. It is straight processing and it is a task of drafting, and re-drafting, revision, elaboration and polishing. Children with bipolar disorder often have such poor frustration tolerance, and very often have a very negative reaction to the demand that they write.

Dr. Luck went on to say:

If a student has trouble self-monitoring, if she or he can’t regulate a flow of ideas and can’t pace him or herself, than each piece of the task that is uncompleted becomes a stress, and the stresses begin to accumulate until the student simply shuts down and refuses to even attempt the task.

Many of these processes that are called upon when a child writes are in the domain of what is called executive functioning. It is increasingly being recognized that a significant number of children with bipolar disorder have deficits in the realm known as executive functioning.

Executive Function Deficits

“Executive functioning” refers to a cluster of mental control abilities, including skills such as the capacity to plan ahead, choose and implement strategies, and organize one’s thinking and actions. Executive functions also include abilities such as maintaining awareness of what one is doing and staying on task, controlling one’s impulses, and monitoring the quality of one’s own performance and making adjustments if necessary.

Executive functioning is performed by the advanced parts of the brain—the frontal lobes and the pre-frontal cortex. Actually, brain imaging has shown that the frontal lobes may be divided into seventeen or more subregions, each responsible for a slightly different kind of work that the human performs. So a problem anywhere in this area will impact the way a child approaches and performs any task.

A Deeper Look at the Executive Functions Critical to the Writing Process

Whenever a human being approaches a problem or a project, he or she must recruit the following executive functions:

• Analyze the problem
• Plan and implement the strategy
• Anticipate problems
• Organize the way the strategy will be accomplished (break it down into its components and effectively assign a time segment for each sub-strategy to be accomplished)
• Monitor the progress and assess whether the plan is working
• Remain flexible and reformulate the plan of attack if the monitoring and assessment process shows it not to be working
• Reassess the new strategy that has been implemented
• Follow the adjusted plan through to the finish

As one can see, strategizing, organizing, marshaling intention into movement, flexibility (changing the approach when it is recognized that the original strategy isn’t working), and constant monitoring are crucial to the completion of any task— and especially to writing and editing an essay, a book report, or piece of narrative writing.

Working memory (also governed by the frontal lobes and a significant part of executive functioning), is crucial to the writing process also.

Working Memory

Working memory involves the ability to hold data in short-term memory while manipulating it toward problem-solving or sequencing it in a logical order. As Dr. Mel Levine writes in A Mind at a Time:

(Many) kids have writing difficulty that stems from weaknesses related to active working memory, the part of memory that allows them to keep track of immediately relevant memory while doing a task. These students tend to forget aspects of the writing tasks while they are writing. For example, while trying to decide if they need a comma or a colon, they may lose track of ideas for the next sentence.

He brings the point home when he says:

Writing requires more memory than just about anything else a student is asked to do in school. Writers need to simultaneously retrieve spelling, punctuation, capitalization, letter formation rules, vocabulary and content information, transitions and connections, and all the other ingredients of written output.

Writing is an enormous academic strain for some students, especially those with graphomotor dysfunctions or significant weaknesses in attention, working memory, and organization of thought.

Graphomotor Dysfunctions

When you look at a child’s handwriting on a piece of paper and see letters poorly formed, a difficulty with the spatial organization of the letters and words on the page, and heavy line pressure, you can quickly realize that the child is having difficulty in the graphomotor domain. This area of disability is called dysgraphia—a glitch between motor memory and its connection to the fingers.

As we mentioned earlier, a sequence of visualization and tiny, precise muscle movements translate the thought of a word into its written subunits (letters) that come together to make that word, that are grouped with other words to make sentences.

All this, plus strong working memory, sequencing, organization, and sustained attention go into the writing process before creativity and mature character development enter the picture. Children with bipolar disorder are often extremely creative verbally, and would be on paper also, if they didn’t often suffer difficulties in the skills that must precede creativity in the writing process.

No wonder children with these problems refuse to write, or produce very little on the written page. If they do write, they “dumb down” the output. Small wonder, then, that teachers and parents (and the children themselves) don’t realize how smart or even gifted they might be. Parents find themselves increasingly anxious, frustrated, and angry at the child who puts off any written assignment until the last minute. They may first try to motivate the child, and when this doesn’t do the trick, negative feelings quickly arise as evenings and weekends go sour—or worse. This is exhausting and demoralizing for the child and the parent. Because writing is a part of every school day, every subject, and most homework assignments, it is important to find out what is really going on to impede the writing process for the student.

Most early and significant learning disorders in the area of written expression will be expressed by the second or third grade (the graphomotor difficulties may be noticed earlier), so it is very important to intervene early when some of the remediation process is age-appropriate. For instance, a very young student will think nothing of using a multisensory approach and sculpting letters in the air or using graph paper; a fifth grader will sneer and become negative before you can explain the purpose of the exercise.

What Tests Would Reveal These Areas of Weakness In Written Expression?

There are many tests that can be administered to determine which areas of the writing process are problematic for a child, and each educational psychologist or neuropsychologist will use those based on his or her training and clinical experience. However, most evaluators on a child study team in a school system will rely on the following battery of tests:

Written Language Assessments

The Woodcock-Johnson Psychoeducational Battery—Revised is a norm-referenced test for ages three to eighty. Among other skills, it yields samples of dictation and writing.

The Wechsler Individual Achievement Test (WIAT-II) is a measurement tool used to gauge achievement skills and to help diagnose learning disabilities for preschool children through adults.

Tests of Written Language (TOWL) —The TOWL-3 is a written language assessment tool used with individuals ages 7 and-a-half to 17. It measures expressive skills in written language including: use of established rules for punctuation, capitalization, and spelling; the use of serviceable syntactic and semantic structures; and the ability to write logical, coherent and sequenced written products.

Tests of Sustained Attention

Tests that measure sustained attention are recommended also. Two that are widely used are the Connor Continuous Performance Tests and the Tests of Variable Attention (the TOVA). Both examine attention over a long period—fourteen to twenty-two and a half minutes—and are performed on a computer. These tests measure discrete aspects of attentional functioning. One or the other is frequently administered.

Tests of Executive Functions

The WISC-IV, the newest version of the well-known intelligence test, has some subtests that reveal executive function deficits. But more comprehensive tests (typically administered and interpreted by neuropsychologists) include:

• The Wisconsin Card Sort
• Tower Of Hanoi
• Tower of London
• Trails A & B
• Stroop Color and Word Test

Another set of tests that a neuropsychologist may administer is to assess executive motor skills. While almost all tasks involve analysis, planning, monitoring, and possible adjustments of strategy (all executive functions controlled by the frontal lobes and pre-frontal cortex), many images and ideas must be translated into sequenced motor acts. These activities most likely involve the pre-frontal cortex and the motor cortex—the strip that begins the frontal lobes. Writing is very much a task of motor sequencing.

Tests that measure executive motor skills include:

• Luria Test of Praxis
• Fine Motor Coordination
• Purdue Pegboard or the Grooved Pegboard
• Hallstead-Reitan Finger Tapping Test

Because explanations of the above tests are beyond the purview of this newsletter, readers might want to read more detail in Chapter 11 of The Bipolar Child, Revised.

What Is the Process of Remediation?

The remediation process will depend on the areas of difficulty that are impacting the child’s written expression.

If the problem is a dysgraphia, and the child is having trouble recalling the shape of letters (encoding) and sequencing them on to paper in a legible fashion, then a multi-sensory approach that is rehearsed and repetitive will help a great deal. A n occupational therapist or a special education teacher may use a special pencil to encourage proper pencil grip, help a child align his or her arms and body in order to write, and use graph paper, or a paper with raised lines, to help the child recognize where to place and how to space letters. There are also slant boards that help the child work at a vertical surface as this promotes the development of proper hand and wrist position and keeps the paper from sliding. This and a foot stool will help the child’s body from collapsing and his or her head from getting too close to the paper.

Special paper and slant boards are usually available in teacher supply stores. Therapro is a wonderful Web site that sells slant boards, pencil grips, and interesting products to promote better writing for youngsters. Visit their Web site at www.theraproducts.com.

Difficulties with spelling and the mechanics of writing such as capitalization and punctuation will also require a systematic, structured, and constantly rehearsed routine. Both the occupational services that help remediate dysgraphia and the remediation of poor mechanics of writing should take place two-to-three times a week and must be written into an Individual Education Plan (an IEP).

Along with special services, an IEP should list a number of accommodations or modifications to the scholastic demands placed on a child with written expression difficulties. These are excerpted from “The Educational Issues of Children With Bipolar Disorder” on the Web site of the Juvenile Bipolar Research Foundation and are used with permission:

I. Writing Disabilities or Dysgraphia

Symptom: Student writes in a slow and effortful manner. The mechanics of writing such as capitalization, using periods or commas and proper syntax, are haphazard and slow to appear.

Accommodations:

• Teach and encourage the student to use a keyboard in class and to complete all assignments.
• Assign a scribe to write longer or timed writing assignments.
• Allow student to tape record classes. Do not penalize quality of note-taking or assume the student is not taking it all in aurally.
• Provide paper copies of notes to the student.
• Allow extra time for assignments.
• Assign a scribe for important tests, or allow the student to give his answers orally.
• Do not penalize the student for handwriting or spelling errors.
• Have the parents investigate voice recognition software, such as “Dragon Naturally Speaking ” (also available on www.dyslexic.com).
• Have the parent investigate the QuickLink Pen. This is a hand-held electrical scanner that allows a student to scan relevant sentences or paragraphs from books, newspapers and articles and to transfer the information to a computer where the notes are printed for the student, bypassing laborious note-taking. Available at www.donjohnston.com.

II. ATTENTIONAL AND ORGANIZATIONAL DIFFICULTIES

Symptom: Student has difficulty staying on task and paying attention for any length of time. Student is very fidgety in the classroom.

Accommodations:

• Seat the student close to the teacher where the teacher can get student’s attention.
• Schedule frequent breaks.
• Offer choices, such as going to a study carrel in the library or to a quiet area outside the classroom.
• Assign a study-buddy (use the phrase study-partner for an older student). The students can focus each other and acquire strategies for learning from each other.

Symptom: The student is disorganized and often misplaces needed books and materials. The student often forgets to bring home assignments and/or fails to turn in work.

Accommodations:

• Use a “travel folder.” This is a pocket portfolio that has necessary papers to complete on the left-hand side (mark this “To Do”) and all completed homework is transferred to the right-hand side (mark this “Completed”).
• Give the student a planner book and have teacher check that daily assignments are recorded properly.
• Email or fax parents a list of assignments and news of upcoming projects or tests.
• Have teacher or aide give the student a prompt before leaving school: “What do I need to do tonight and what materials would I need to accomplish it ? I need: my coat, my recorder, my math book, my study sheet for French, my planner, my lunch box, my travel folder (French sheet is there...).” The teacher or aide could photocopy lists of materials and clothing and have student check items off as they are put in the bag. Student must be taught to pack backpack to return to school the same way with a prompt such as “What do I need for school today?” (A parent has to help out here.)
• Provide a second set of textbooks for the home work area.
• Teach the student to number assignments in the order in which they should be done before beginning a homework session (thus they will focus and begin a mode of strategy). Have the student start with an assignment that is short and easy, but avoid saving the hardest or longest assignment for last. Have the student estimate how much time it will take to complete each assignment and measure the estimates against the actual time (these students have difficulty with time management). Have them use a stopwatch to assign chunks of time to each step of a study plan which will help move them on to the next step.
• Teach the student to preview questions at the end of each chapter to focus him or her on important concepts. The student should also preview photos, captions, and headings throughout the chapter before reading and when reviewing for a test.
• Color-code subject folders and notebooks to match textbooks. For instance, if the math text is orange, place an orange strip of tape on the math folder and notebook so that student can quickly locate and assemble all materials needed for math. If school requires the books to be covered, color coordinate the books and folders.
• If the student uses a locker, teach him or her to place all morning text books, notebooks, and folders on top shelf of locker, and all afternoon materials on lower or bottom shelf. This will help organize the student and ensure that he or she goes to class with the correct materials. Have the student (with the help of an assistant if necessary) clean out locker at least once a week. Schedule that cleanup on Fridays to ensure that P.E. clothes and needed materials arrive home for weekend use.

One additional note: Children in elementary school onward will be given city-and state-wide exams that use prompts in the writing sections (the children are supposed to use the prompt as a jumping off point and compose a narrative story that is interesting and rich in detail). This is a major stumbling block for children with disorders of written expression. While researching this newsletter, we came across a truly valuable book by Barbara Mariconda called The Most Wonderful Writing Lessons Ever. It deconstructs the entire process and helps children and adults understand the building blocks that make up good narrative writing. Though the book is advertised for grades 2-4, it is used in high schools, and teachers and parents will find this book particularly helpful.

In Conclusion

Because the writing process is so integral to every subject in school, it is easy to see that a child struggling with written expression will find the entire day torturous and humiliating. In the late afternoon and evening—typically difficult times for children with bipolar disorder—the child will feel especially burdened as he or she anticipates the frustration, fatigue, and failure that will accompany any homework assignments that require written work.

Children with bipolar disorder are coping with so many other difficulties…. If parents and teachers watch mindfully for any struggle in the area of written expression, and move quickly to begin remediation and to institute accommodations, they can significantly lessen that burden. Early and sympathetic intervention will make a tremendous difference—in the early years, and in the vastly more complicated and difficult years of middle school and high school.

We’ll write again soon. Meantime we wish you and your families peaceful summer days, and, as always, we look forward to hearing from you.

All best,

Janice Papolos and Demitri Papolos, M.D.

The authors wish to thank Dr. Dana Luck, and Karen Williams for their contributions to this newsletter.

Bibliography

Luck, Dana. Telephone Interview of May 23, 2004.

Levine, Mel. A Mind At A Time. New York: Simon & Schuster, 2002.

Papolos D. and J. The Bipolar Child, Revised. New York: Broadway Books, 2002.

Web site of the Juvenile Bipolar Research Foundation (http://www.jbrf.org).

We all experience bouts of boredom in life, but children and adolescents with bipolar disorder seem particularly prone to them. It often seems difficult for these children to become engaged with projects, or to set goals, and though a parent can offer any number of choices of activities, the children can’t seem to invest in any of them. They whine and complain constantly of being bored.

Often the children’s response to this internal state of boredom is to provoke a stimulus from the environment—from a parent, usually, or from a sibling. They create chaos, despite the fact that it so often results in family members becoming angry at the provocateur in their midst. One mother wrote and described her thirteen-year-old daughter this way:

She complains and whines constantly about being bored. The Internet is the first place she goes to try and find something to do—either instant messaging or emailing friends. I have to be very careful that she doesn’t use the Internet in inappropriate ways. The ability to get online and connect with someone —anyone really—when they are in that bored state is very dangerous in my mind.

If she can’t find a friend to instant message online, her next pattern is to get on the phone and to try to call anyone she knows. She is always trying to set up impossible activities and asking a friend if she can do these things without my even knowing about it or approving it.

She went on to say:

When she realizes she has to stay at home, she starts “playing” with her little brother and sister. However, this playing is more in the form of torture. She tickles Maddy to the point of crying. She jumps into Jared’s Nintendo game and makes him lose. She chases them, annoys them, pretends she is playing with them and lures them into a false sense of security and then starts bothering them in any way possible. They cry and she seems happy not to be bored anymore.

Another mother emailed us and described her son’s boredom and the provocative behavior that often follows this state:

Oh, yeah. Boredom “R“ Us. Because Jamie seems incapable of turning his thoughts and impulses into a creative activity, he creates busyness that brings him no real satisfaction. He begins to "go on the prowl" and he very soon becomes intrusive, provocative and demanding. I think he’s looking for that missing satisfaction for all his busyness. As the provocateur, he will seek out his brother’s attention and then either provoke or fabricate an offense. He’ll go into his brother’s room while his brother is on the computer, lie on his bed and make annoying sounds until Sam can’t take it anymore and starts calling Jamie stupid, fat, or worse. Then, naturally, Jamie will yell that Sam is torturing him and the situation deteriorates from there.

She continued:

Sometimes Jamie will invite Sam into his room to play with something he has previously withheld, usually a computer game, but sometimes a gaming magazine that he knows his brother will devour. Then when Sam takes him up on the offer, Jamie complains that Sam is not sharing and is taking over. Chaos ensues and we order them into their separate rooms.

Why are these children so often bored, and why do they need to provoke someone close to them and create such chaos and bad feeling?

The answers are multi-determined and no doubt a combination of psychological and biological factors.

Some Possible Reasons For This State of Boredom

Adults suffering with depression experience low-energy states and often a distinct lack of pleasure in things they previously enjoyed. This arid state is called anhedonia. In Overcoming Depression, we quoted a woman who was experiencing the clinical symptom of anhedonia and she described it this way:

The most awful thing was that I realized that my days had been composed of little moments of anticipated pleasure: that first cup of coffee in the very early morning, the inner thoughts that made me chuckle, a browse through a book store, the satisfaction of a job or chore completed…Now these moments failed to hold the crest of pleasure—everything was flat and gray. Life seemed locked away from me and I was filled with an unspeakable dread.

When the mind is laid barren of thought, the imagination cannot make the necessary leap into the future, and the individual experiences himself as out of time and isolated from the ongoing currents of life. He cannot reconnect.

This slowed-down state where nothing is enjoyable may—in children—present as boredom. Children with bipolar disorder are both easily excited and easily disengaged and bored (this dysregulation would make sense in light of the quicksilver shifts between high and low states, as well as the mixed states in which they are often trapped).

For many children the provocative behavior that seems to follow a period of restlessness and boredom may be a way of connecting and even showing affection. It can put a child who can’t connect and is in a slowed down state in control and give him or her this sense of connecting.

Executive Function Deficits

Sometimes the boredom is a result of the deficits that many of the children have in the realm of executive functions. As we wrote in a past newsletter, The Irrepressible Agendas of Bipolar Children: “Many of these children have deficits in the frontal lobes--regions that govern the processes known as executive functions. The frontal lobes coordinate many things, including reasoning, problem solving, strategizing, working memory, attention, self-control, motor sequencing, intention, and flexibility of thought.”

If children have difficulty paying attention, planning, strategizing, bringing working memory to bear on a problem, and relinquishing a task when it proves not to accomplish a desired effect, imagine how difficult it would be for them to sink their teeth into something and move themselves along toward a feeling of mastery, reward, and accomplishment.

These executive function deficits, the slow-down of depression and the often accompanying anhedonia, may cause these children to lapse into periods where they cannot connect and get no charge from the environment. They may feel they have no choice but to force the issue and make the environment respond to them. In other words, they feel compelled to provoke—even if the provocation results in negative responses from those who are being pulled into their bored orbit to “fix” the problem.

Few people realize that the provocation may be a child’s desperate attempt to escape what is experienced as an intolerable lack of stimulation. The goal, however, shouldn’t be to abolish the behavior, but to understand it and attempt to modify it. Although it is a maladaptive behavior, it is a coping mechanism. These children are trying to cope with something that feels very bad inside.

On the surface it may present as boredom but several questions arise: Is this a mood state? Are they prone to boredom because they are experiencing a low level of depression and they can’t engage and feel pleasure and reward? How much of the boredom is a symptom of the disruption in their object relations? If they have difficulty creating and sustaining good relationships, does it make it difficult for them to connect and do they shut down into a desolate, lonely, and scary inner state? What is happening on a biological level?

A Few Biological Clues

Researchers have long known that there are “pleasure centers” in different parts of the brain. As Dr. David E. Commings writes in his book Tourette Syndrome and Human Behavior: “Correlations between the pleasure centers of the brain and the region rich in specific neurotransmitters helped to place pleasure on a chemical as well as on an anatomical basis.”

The neurotransmitter, dopamine, has long been implicated in the brain's system of reward. Since dopamine neurons pass to the frontal lobes, this important area of the brain is involved in the reward pathway. In animal studies, an inhibition in dopamine activity in the nucleus acumbens (one of the primary dopaminergic nuclei in the brain), results in abnormalities in motivation, reward, and pleasure. It is quite possible that some form of dysregulation in dopaminergic pathways leads to the experience of anhedonia--a lack of the ability to experience pleasure--and its converse, elation.

But How Can These States Be Handled in Real Life?

Until we understand the biology of these states (and even then), isolating and labeling, and understanding the problem would be extremely helpful for the child and the family. We spoke with Dr. Paul Schottland, a cognitive psychologist in Florham Park, New Jersey. He first talked about the child’s need to provoke and stimulate others and thus him-or-herself. He explained:

When the child teases, he or she begins to laugh. The child gets a charge out of it, and feels in control (the other person feels unable to stop it). This, in turn, makes the child feel power, authority, and superiority—feelings these kids rarely feel in an encounter with others—and this puts the child in a better mood state. This power and sense of control can be almost narcotic-like to the child. But typically the person at the other end of the teasing becomes incensed and when this "narcotic" wears off and the child sobers up, he or she often feels so badly and such remorse as the realization hits that things have gone badly once again.

The child doesn’t understand the need for this behavior—it seems to right the problem—yet people around seem to feel only anger and exasperation (and who can wonder why?).

Dr. Schottland advises:

The first step may be to understand some of what’s happening inside the youngster and talk about it, or show the child you are sympathetic. The response from the adult can be more compassionate and the adult can view the child in a more benign light. This opens the possibility for teaching the child a more adaptive way of coping with these very dark and scary feelings. If the adult can help to "head off" the mood state and modify the behaviors before they become intractable and ingrained in the personality, relationships can repair and become more satisfying and warm.

First Things First

Before anything can be accomplished, the child must be medically stable. Then, a complete neuropsychological evaluation will help determine if the child has executive function deficits and which ones they are (see Chapter 11 of The Bipolar Child, Revised for a complete battery of tests to explore these domains).

Once these bases are covered, cognitive therapy can be extremely important and helpful. Dr. Schottland talks to his young patients and addresses the healthy part of them first. He tells the child:

I think you do this for a reason. There is a very healthy part of you that can control or modify this behavior. You’re not always in this mode—you’re a nice, sweet, kid. But sometimes you go into this teasing, provocative mode that can be very upsetting to the people around you. When does this get activated? When you have nothing to do or when you are upset and feeling down—bored inside, and it feels so bad to you. So when you feel this (or there is no fun happening for you) you start bothering your family and it makes you not feel bored anymore. Sometimes the teasing is funny for a bit and you may see others laughing, but when it goes on too long, or when you don’t listen when people ask you to stop, it gets you in trouble and people think badly of you.

He continues, explaining to the child:

These behaviors aren’t you. This part of you is very small. You are so much more than this. Everyone has a little bully inside of them, and everyone likes to tease, but this can get activated in you and you find it hard to stop.

Usually children respond to this description and the conversation gives them a sense that the behavior might be managed by them.

Dr. Schottland uses imagery with the very little ones and asks them to picture sending that little bully to its room. For older children he instructs them to do something more productive with the feelings. “Put it into words,” he says. “Tell your mother you’re feeling so bad and so bored and it makes you want to start teasing or taunting someone. You need to have a catalogue or laundry list of things that might take you away from that state.”

The child and Dr. Schottland prepare this list and begin a strategy to stock the house with what’s needed when they feel themselves going into this mode. He and the child enlist the help of the parent because these items must be in the house and available for such moments. A trip to the store is too late to stop the mode from kicking in, and once it does, the child is off kilter until it burns itself (and the immediate family) out.

Hobby shops are a godsend says Dr. Schottland. Rockets, ship models, art work, video games or movies held in reserve for just such times.

He also warns that the car is the “hell-on-earth mobile” for parents with bipolar kids. This is where they get extremely bored and they begin to nudge their siblings (they also may be hypersensitive to the closeness of bodies and loudness of sounds in the back seat of a car). The car is a prime breeding-ground for blow-ups.

Dr. Schottland cautions parents never to get into a car with the kids—no matter how short the ride—without what he calls a bag of “distractors”: hand-held video games, CD players with headsets, a movie if the car is outfitted with a DVD or tape machine. “Use the child’s considerable ability to hyperfocus to the child’s advantage,” he says. “Parents should understand that these are therapeutic tools that result in better management of the problem and stop feeling guilt about appropriate video games and movies to keep things running smoothly.”

More Ideas That May Work

The mother we interviewed with two children who have bipolar disorder told us the following:

My younger child is easier to direct out of this mode, but for him, boredom equals hyperactivity. When he is bored he starts running around and jumping all over the place. He literally will just run between two points. He needs a physical outlet for this emotional state. If I can, I go out and jump on the trampoline with him. I offer to take him rollerblading. The hard part for me is that it requires that I do something with him. When he is in this mood, he will not play alone or with his younger sister. If I am not in a position to drop everything and become a camp counselor, he too will escalate to the point where he starts bothering his little sister—teasing her and chasing her just to get a reaction.

This family is very complicated because the father also has bipolar disorder and if the mother can’t get either child out of this mode soon enough, the kids end up picking on the younger child and using her as a tool to vent their needs. Of course the noise level rises as they start chasing each other all over the house and screaming and complaining. “If my husband is home,” she explains, “he yells, the kids cry, the kids hit each other, chaos ensues and what I call ‘the bipolar bounce’ is in full swing.”

She spoke about some other coping mechanisms:

The best way I know to try to combat this is to keep my kids busy and scheduled. It really helps that Lizzy is now ice skating every day after school for three hours. The physical exercise is great, and just removing her from the after school crisis hours at home helps. The ability to give each of them some one-on-one attention is a good way to side-run this problem. I can’t do it all the time, but I try to spend some time doing something physical with my son (and he chooses this as often as he can).

Weekends are the hardest. Having unstructured weekend days sounds like heaven to me personally, but they are a recipe for disaster here.

She then wrote about some action plans that can be helpful at times:

When I am really at my wits end and need to get the kids out of the house, I now take them to a nearby mall that has a sporting goods store with a climbing wall in it. It doesn’t cost anything and they can each have a turn or two. I promise them a milkshake before we go in so they focus on that and not some other expensive sports item they can suddenly seize upon.

This mother admitted that she is often not in the mood nor does she always have the time to drop everything she is doing just to prevent her child from getting bored. “Sometimes I let a child move a T.V. into his or her bedroom to watch his or her own special movie alone,” she explained. “Sometimes I just call Grandma and ask her to take one of my kids for the afternoon or for a sleepover (Maddy is at my mother’s as I write. I sent her over last night to get her away from Lizzy who was bothering her!)”

Jamie’s mother sent a follow-up email in which she said:

After reading over my email yesterday, I realized I’d wandered off track and left out one management technique that actually is helpful. When I see a block of free-time coming—a “boredom trouble spot”—I try to come up with an assignment. Jamie loves pens and markers and doodling, so I’ll ask him to draw something about a Web site he’s been into, or to make a birthday card for someone (a child or adult). This actually keeps him busy for a while—when he’s engageable. If it’s a snow day we’ll let him loose with the slow blower, which is one of his favorite things. We have begun to have success with getting him on the elliptical trainer while he watches a movie (we’ll see how long this lasts). On a single day off from school you need to have all of the above….and you must be prepared that all your camp counselor scheduling may be met with: “I hate that; I don’t want to do that,” and a string of negative and surly responses to each one of your enthusiastic ideas and suggestions. It all depends on the mood of the child.

It’s good to remember that these are transient states, and will resolve. (However, we understand that this is little consolation as the time stretches interminably in front of you and you watch the child begin to go on “the prowl” and begin to light on you or a sibling for this much-needed spark of life.) But, as Dr. Schottland says: “If the parent understands why the child feels he or she needs this behavior as an antidote to an uncomfortable inner state, the parent can intervene and remind the child of the typical outcome of such behavior.

Dr. Schottland suggests saying something like: ‘Daniel, you’re going into bully mode. It’s starting to take over—can you see that? Can you remember that everyone gets upset at you when this happens? Let’s see what else we can do to make you feel less bored.’ Dr. Schottland cautions that a parent will not always be successful in catching it at the right moment. However, this reminder may increase the odds that the child can gain some control over time.

How the Siblings and the Bipolar Child Can Be Helped

It should be underscored that sometimes the provocation starts out as a sort of game and that the children may have fun for a while before it deteriorates and becomes taunting and upsetting for all players. In clinical work with families, one of us (DFP) focuses on the events that are set in motion as the boredom-provocative behavior dynamic caroms across the household.

In this context, the family members talk about what fun it all can be initially (the kids actually may all see it as fun—they don’t know any other way to play). The question is: how can it be fun without it getting out of control? Here the parent is asked to estimate how long the teasing and chasing goes on before the situation turns ugly. If the parent estimates about five minutes, an agreement must be made by all involved that after four minutes there will be a time out and everyone will go into his or her room for a ten-minute break (just like in sports).

If you turn it into a game with rules, it gives the children an external boundary and gives all the children a sense of having fun but being in control and feeling a sense of mastery. Actions can start and stop without screaming and bad feeling.

The first attempts at this game with rules and boundaries should be looked at as trials and the children must be told that they can fail. But for children who have difficulty sequencing and anticipating outcomes so that they can alter them beforehand, and who can’t change set quickly and relinquish what ever they’ve set off doing, this “game” may help them do all that and make them feel better. It “stretches the muscles” that aren’t strong in the domains of executive functioning.

In Conclusion

We hope that this newsletter sheds some light and understanding on yet another set of feelings that the child with bipolar disorder is attempting to cope with, and that a compassionate approach may help him or her feel not quite so alone, not quite so scared, and in a better position to solve this uncomfortable problem of boredom in a more adaptive way. The children can be helped to tolerate periods of boredom. They need not always fear that they are falling down the rabbit hole and therefore need to create chaos in order to get a toehold and pull themselves free.

We also hope this discussion helps parents feel more in control of the situation and feel less dread of an upcoming “boredom trouble spot.”

Parents should always try to remember that though the children are prone to boredom—especially in the younger years—eventually most of them get engaged with something that they are good at and like, and boredom presents less of a problem as time goes by.

We know that not one of you signed up as “Camp Counselor/Referee” when you became parents, but we salute you for striving so hard to solve these very difficult problems for the children you love.

With great admiration,

Janice and Demitri Papolos, M.D.

The authors wish to thank Dr. Paul Schottland, Cheryll Hart, Cheryl Matalene, Jeanne Langer, and Karen Williams for all their help in preparing this newsletter.

Bibliography

Commings, D. Tourette Syndrome and Human Behavior. Duarte, California: Hope Press, 1990.

Papolos, D. and J. The Bipolar Child, Revised. New York: Broadway Books, 2002.

Papolos, D. and J. Overcoming Depression, Third Edition. New York: HarperCollins, 1997.

Papolos, J. and D. “The Irrepressible Agendas of Children With Bipolar Disorder.” The Bipolar Child Newsletter, October, 2002, Vol. 12.

Salamone, JD, Cousins, MS, and Snyder, BJ. “Behavioral functions of nucleus acumbens dopamine: empirical and conceptual problems with the anhedonia hypothesis.” Neurosci Biobehav Rev , May (21): 341-359.

Schottland, Paul. Telephone interview of January 22, 2004.

The preliminary findings of the largest on-going study examining children at risk for bipolar disorder. Can an early symptom profile be detected? The clinical features of hyper-alertness and oversensitivity as early predictors of a bipolar disorder.

Latest News:

• Juvenile Bipolar Research Foundation Genetic Study
• Conferences in Colorado Springs and Ashville, North Carolina featuring Demitri Papolos, M.D.

In the spring issue of 2001, we wrote a newsletter entitled What Can the Amish Teach Us About Early-Onset Bipolar Disorder? It focused on a study of adult members of the Old Order Amish in Lancaster, Pennsylvania who suffered with bipolar I disorder. At the end of the newsletter we informed our readers that the principal authors of the study, Dr. Janice Egeland and her colleagues, were conducting a long-term study with 210 children (many who had a parent with bipolar I disorder). One of the goals of the research was to determine if an early-symptom profile could be detected before the onset of illness in the at-risk youngsters. We promised we would interview Dr. Egeland again and report on her findings.

In July of 2003, the preliminary results of the largest, most methodologically rigorous prospective study of children at risk for bipolar disorder was published in the Journal of the American Academy of Child & Adolescent Psychiatry. It is entitled “Prospective Study of Prodromal Features for Bipolarity in Well Amish Children,” and we think that this study is such a benchmark and that it archives such a treasure trove of information that we wanted all of our readers to know about it.

Why the Amish Are a “Living Laboratory” For Research In Bipolar Disorder

In many ways the Amish community provides a natural laboratory for all genetic and clinical and phenomenological research. It is a well-defined, closed population with little migration into or out of the community. The community can trace its ancestry back to 30 progenitors in Switzerland, and it maintains extensive genealogic records. The Amish community encourages a high birth rate, so a researcher can study large families. It is also important that this community prohibits the use of alcohol and drugs—substances known to complicate prenatal health as well as diagnostic ascertainment and assessment.

Finally, while the Amish have no more bipolar disorder than any other population group, they have always viewed bipolar disorder as a medical condition (“Siss im blut”—it’s in the blood, as they say), and they seek medical care for what they view as medical illnesses.

Dr. Egeland has been conducting genetic and epidemiological studies among the Old Order Amish since 1976 and has had a long-standing, trusting relationship with this community. Her earlier studies have identified families with a high loading of bipolar I disorder under genetic linkage study, and she can now look at the fourth and fifth generation of children as she has known many of their parents since the parents were babies themselves.

The Study Design and the Hypothesis

The Child and Adolescent Research Evaluation (CARE) program of the Amish study was initiated in 1994 and was designed to follow a group of 210 children and adolescents in two samples: a bipolar I sample and a control sample. The bipolar I sample were the children of a parent who was known to have bipolar I disorder. The control sample consisted of children who had a well parent whose sibling had the disorder, and a group of children with a family history negative for any psychiatric illness.

The hypothesis of the study was that there would be a gradation of risk for bipolar disorder: with children of one parent with the illness having the highest risk, followed by children whose parents were well but had a sibling diagnosed with the disorder (nieces and nephews), and by children in families with no history of the illness having the lowest rating of risk.

If this hypothesis were correct, the goal would be not only to gauge the genetic risk factors, but to identify the temperamental features and behaviors that might be predictors of an eventual manifestation of the illness.

At the time of recruitment in 1994, 14 candidate bipolar I families (8 fathers and 6 mothers with the illness) were invited and agreed to participate. A matched control group was assembled with children of same-sex psychiatrically-unaffected parents who had a sibling with the illness. Because it was not possible to obtain a sibling control for all the families, the parent with bipolar disorder was matched by sex, age, and family size to an unrelated Amish man or woman with a family history that was negative for psychiatric illness.

The final sample of 210 children consisted of 100 children from 14 families where a mother or father had bipolar I disorder; 77 children from 9 control families where the parents had a sibling who had bipolar disorder; and 33 children from four control families with a history negative for the illness.

How Was the Information About the Children Collected?

In order to launch the study that would follow children and adolescents over a twelve- to fifteen-year period, Dr. Egeland and her colleagues and a group of child psychiatrists, child development scientists, a pediatrician, and Amish advisors developed a formal schedule of questions that became known as the CARE Interview. This interview covered medical and developmental histories (Part A), a health narrative (Part B), and a third questionnaire with 69 inquiries related to a wide range of symptoms and life events (Part C). Part C’s questions were considered comprehensive enough to reveal potential early or prodromal features of bipolar illness.

The parents were asked whether their child was “noticeably different” from “other boys and girls” his or her own age. In the Amish community there are such well-defined roles for children, with specific chores expected at various ages that role performance (and any possible impairment) can be detected quickly.

Amish children have no homework after school. They go right home, go upstairs and change their clothes and go out and do their chores. Therefore, if these chores are completed in an inconsistent or spotty fashion, the parents realize that something is wrong. This is important because “role impairment” (functioning) is an element in psychiatric assessment. Hence, parental rating of chores gives a measure of “wellness” for each child annually.

How the Children Were Evaluated for Possible Risk

After a mother answered Part A of the CARE Interview, both parents answered Parts B and C, and the narrative file for each child was presented randomly to the CARE panel. This panel was composed of two board-certified child psychiatrists, a board-certified general psychiatrist, and a clinical psychologist.

All members of the panel were totally blind to the children’s identity or family history.

The panel members independently coded CARE narratives in sets of 10 children and recorded their clinical opinion for risk of developing a bipolar disorder. The options the doctors had to code these well children included high risk, moderate risk, low risk (these codes indicated the highest risk ratings); well with a BP tag; or well with no evidence of risk.

The“ BP tagged” risk category was used for children who were well, but who were manifesting some clinical features that suggested a possible onset of bipolar disorder in years to come, but who did not at this time warrant a risk rating. Risk rating represented a “clinical judgment” based on the substantial clinical experience of the panel, and there had to be consensus about each rating.

Which Group of Symptoms Occurred Most Frequently in Which Group of Children?

When all the data were assembled and the statistical analyses performed, the children of a bipolar parent were reported to have manifested more clinical features on the coding sheet than the control group, and the children of well parents who were siblings of a bipolar I patient manifested more clinical features than the children with no family history of psychiatric illness.

To add in the statistics: When rated for risk, 38% of the bipolar sample (compared to only 17% of the control sample) had high-moderate-low -ratings. Yet the vast majority of children in the control sample who had risk ratings, turned out to be the children who had an aunt or uncle with the illness (83%).

Similar to other studies of genetic risk, the children at highest risk had a parent with the illness. Children with a second-degree relative had a reduced risk but this risk was still higher than the risk for those who came from families negative for any psychiatric disorder.

Because we don’t want anyone to misinterpret the statistics, it is important to point out that the 38% figure is not the genetic risk factor to a child of a parent with bipolar. These Amish children are well with certain symptoms/features, and--depending on how many of the children onset with the illness--these symptoms/features may be suggestive of an early symptom profile for bipolar disorder.

The genetic risk to a child of one parent who has the illness is usually pegged between 20 and 30%. However, no one knows which factors may forestall an illness from developing and which genes might even be protective.

Which Clinical Features or Symptoms/Behaviors Did the At-risk Children Have?

The children who had a parent with bipolar I disorder had a statistically significant higher frequency for 10 clinical features when compared to the control group. Listed alphabetically they are:

• Anxious/worried
• Attention poor/distractible in school
• Energy low
• Excited
• Hyper-alert
• Mood changes/labile
• School role impairment
• Sensitivity
• Somatic complaints
• Stubborn/determined

It is interesting that the temperamental features of sensitivity, hyper-alertness, being anxious/worried or nervous appeared to be continuous as the parents responded to these with remarks such as “always” or “by nature.” However, half or more of the reports about decreased or increased energy and mood were episodic and all but one report on anger/temper showed as periodic rather than continuous.

This differs dramatically from the ultra-ultra rapid-cycling pattern of mood, energy, irritability and temper problems reported in so many non-Amish children, and raises questions about environmental influences on the presentation of symptoms and course of illness.

The Temperamental Features of Being Hyper-alert Or Overly Sensitive

Seventy percent of the children at risk for bipolar disorder had parental reports mentioning how “hyper-alert” and “overly sensitive” the children were. In the retrospective study that Dr. Egeland reported on two years ago, one quarter of the adults with bipolar I disorder had hospital records that noted “overly sensitive compared to others” prior to onset. (That figure may have been higher, but these were chart reviews of first hospitalizations and the symptom profile was not probed systematically upon admission.)

Parents and teachers in the Amish community who identify a child as “overly sensitive” refer to a child who has a heightened sense of awareness. If one observes such children, their “social skin” appears to be overexposed. They may seem “hyper-alert” to the feelings of others—peers and adults alike. It is as though an electrical field surrounds these youngsters and their antennae pick up all possible signals.

According to Dr. Egeland, “They seem to notice everything: how someone is dressed, whether their shoes are shined…they get very close to you and seem to need some physical contact. If another child gets stung by a bee, this child will feel so deeply that she will cry for the injured child.”

It has long been known that people in a manic state are hyper-alert, hyper-vigilant, and hyper-sensitive. According to the authors of the Amish findings, these features of being “overly sensitive” and “hyper-alert” could be early predictors of bipolarity.

Dr. Egeland then mentioned something that struck us when she added: “These children feel things very intensely and they are oversensitive to color.”

Parents who participated in the original survey for The Bipolar Child also mentioned this overall sensitivity; and one area of particular sensitivity was to color. One mother described her young daughter as “very sensitive in the visual realm. She is drawn like a magnet to some designs and colors, beautiful paintings, landscapes, and repelled by others, as strongly as she reacts to odors and tastes.”

When one looks at the art of Peter Paul Rubens, Vincent Van Gogh, Maurice Utrillo, Edvard Munch, and Jackson Pollack (all of whom suffered with manic-depression) it is easy to see this important sensitivity to color.

The Symptoms and Cycling Patterns Of The At-Risk Amish Children In Contrast To Non-Amish Children

More severe symptoms and symptoms of mania tend to manifest later in Amish children—most likely in adolescence. In this population, symptoms were showing up in the prepubertal years, going underground, and reemerging in adolescence. Also of interest, the Amish children of a bipolar I parent were not at a higher risk for patterns of disruptive behaviors, oppositional behaviors, or the hyperactivity so often seen in prepubertal children diagnosed with the disorder in communities outside the Amish culture. The authors write:

It is interesting that in our prospective study, clinical features such as mood, increased and decreased energy, decreased sleep, and anger/temper were noted to occur periodically in 50% or more of the reports for children of a bipolar parent. Other studies have suggested that the most frequent pattern of prodromal symptoms of bipolar disorder is characterized by continuous and chronic manifestations of irritability, mood dysregulation, and rapid cycling with little inter-episode relief.

What accounts for these differences in presentation is not known, but it is interesting to speculate whether the absence of alcoholism within the Amish community may differentially influence the presentation of the illness in comparison with non-Amish families.

A Case Vignette

To demonstrate a possible prodromal syndrome of one of the youngsters in the CARE Program, take a look at Rebecca’s story:

Rebecca was born at home after a long labor and was a fussy, colicky baby. Her infancy, growth and development were normal. At age 6, she was reported to be bold, stubborn, overly attentive, and slower to respond to discipline than her siblings. She was still “hyper-alert” and sensitive when 10- to 11-years old and tended to want to know “everything about everybody.” Becky was said to “worry like an adult about grown up” things. By age 12, she had outgrown these traits and was a good student. Other than headaches and feeling faint, nothing noteworthy was reported for her early teens (ages 13 to14).

Three of the panel rated Becky as well. One child psychiatrist rated her for low bipolar risk: “It is difficult for me to rate her as outside the limits of ‘wellness’ but the combination of symptoms noted make me wonder; they seem to form a ‘mini-cluster.’” After group discussion, the consensus was recorded as “well, with a BP tag.”

In the fall season after her 15th birthday and our CARE update, Rebecca suffered a sudden “breakdown” which lasted three months and required treatment. The updated information was read and independently rated by the clinicians. Becky was moody and sad; had significant weight loss, insomnia, loss of energy and interest, and self reproach; could not focus and think clearly; and was fearful about dying and delusional about death. The CARE panel agreed that she met standard diagnostic criteria for a major depressive disorder. The clinicians upgraded the risk rating from the original “well, with a BP tag,” to a “moderate” risk rating for bipolar problems in the future. This decision was made blind to pedigree identification and the fact that Rebecca’s father is a BPI patient.

Relevant to this pattern was a 3 to4-year prospective study of predictors for those most likely to shift from unipolar to bipolar disorder. Predictors, with high specificity for bipolar, included a depressive cluster with rapid onset of symptoms, a family loading for mood disorder and mood-congruent psychotic features. Becky fits this prediction.

Only time will tell whether or not Becky will convert to the bipolar I form of the disorder, however, we should keep in mind that Dr. Barbara Geller of Washington University in St. Louis reported on a ten-year follow-up of a group of 72 children who were originally diagnosed with depression before puberty (the average age at diagnosis was 10). By the age of 20, nearly half--48%--had developed the bipolar form of the disorder. Since children with ADHD were excluded from Dr. Geller’s study, it is possible that these rates of switching would have been even higher.

It bears saying that antidepressants should be used with utmost caution in children presenting with a syndrome that seems to present so squarely in the depressive spectrum. All efforts toward unearthing family history and any possible symptoms that may be temperamentally in the bipolar spectrum should be examined repeatedly before consideration of antidepressant treatment.

What Next?

According to Dr. Egeland and the other authors of this article, the research in the CARE study now rests on the ultimate outcome of a bipolar disorder diagnosis for a well child correctly designated “at risk.” The researchers plan to follow the children for 12 to15 years and will be reporting new findings in the literature throughout that period of time. A new article is expected sometime next spring.

In the meantime, genetic markers in one or more chromosomal regions for susceptibility gene(s) have been established in adults with bipolar disorder in the Amish community, and the researchers are collecting DNA from a number of the children in the CARE program. As this program is the only prospective study with the goal of comparing clinical prediction and genetic patterns for bipolar disorder, future reports from the Amish study will no doubt do much to expand our knowledge of the genetics, the early symptoms, and the course of childhood-onset bipolar disorder.

In Conclusion

Amish children live in a completely pacifistic society where anger or violence are never displayed, and where they are expected to be well-behaved, submissive to authority, quiet and non-intrusive around adults. Their opinions are never asked for or expressed. These children have never seen television, the nightly news or scary or gory movies, and they have never played Nintendo. They use no electricity and tend to go to sleep soon after nightfall and arise early with the sun—their sleep patterns are extremely uniform. They also have many brothers and sisters who act as role models, and are surrounded by cousins and peers who follow the traditions of the community closely and thus provide an additional abundance of role models. The social structure that surrounds children in this community is practically impossible to duplicate.

And yet, Amish children who have early symptoms of a possibly evolving illness cannot always conform to the expectations of their culture—anymore than can children suffering with these symptoms in the world outside.

We’ll write again soon. In the meantime, as always, we look forward to hearing from you. May the holidays find harmony within your homes.
Janice Papolos and Demitri Papolos, M.D.

BIBLIOGRAPHY

Biederman, J., Mick, E., Faraone, S. “Pediatric mania: a developmental subtype of bipolar disorder?" Biological Psychiatry 2002; 48:458-466.

Egeland, Janice A., Jon A Shaw, Jean Endicott, et al. “Prospective study of prodromal features for bipolarity in well Amish children.” Journal of the American Academy of Child & Adolescent Psychiatry 2003; 42:786-796.

Egeland, JA, Hostetter AM, et al. “Prodromal symptoms before onset of manic- depressive disorder suggested by first hospital admission histories.” Journal of the American Academy of Child & Adolescent Psychiatry 2000; 39:1245-1252.

Egeland, J. and Allen, C. Telephone interviews of November 4 and 5, 2003.

Egeland, J. Email correspondence of November 4, 2003.

Geller, B., Williams, M. “Prepubertal and early adolescent bipolarity differentiate from ADHD by manic symptoms, grandiose delusions, ultra-rapid or ultradian cycling.” Journal of Affective Disorders 1998; 51:81-91.

Geller, B., Zimmerman, B., et al. “Bipolar disorder at prospective follow-up of adults who had prepubertal major depressive disorder.” American Journal of Psychiatry 2001;158:125-127.

Hershman, JD. and Lieb, J. Manic Depression and Creativity. Amherst, NY: Prometheus Books, 1998.

Papolos, J. and D. “What can the Amish teach us about early–onset bipolar disorder? “ The Bipolar Child Newsletter January 2001, Vol. 6.

http://www.bipolarchild.com/newsletters/0101.html

Papolos, D. and J. The Bipolar Child, Revised. New York: Broadway Books, 2002.

Strober, M. and Carlson GA. “Bipolar illness in adolescents with major depression: clinical, genetic and psychopharmacologic predictors in a three-four-year prospective follow-up investigation. Archives of General Psychiatry 1982; 39: 549-555

The authors wish to thank Dr. Janice Egeland and Mrs. Cleona Allen for their pioneering work in this field and for their much-appreciated contributions to this newsletter, and a thank you as well to Catherine Schwartz, Karen Williams, and Jeanne Langer.

A mother from New Jersey wrote and described a scene that occurred not long ago as she was driving her nine-year-old son to soccer practice. A commercial for an anxiety clinic came on the radio and the announcer asked: “Do you worry a lot about things that don’t seem to bother other people? Are you afraid of having anxiety or panic attacks?; Are you worried that bad things may happen to people you love?; Do you feel nervous when you are out with other people—even if you know them?….” The youngster’s symptoms of early-onset bipolar disorder were understood and well-treated pharmacologically, so this mother was shocked to hear her son murmur in response to the questions: “I have all of those.”

With his mood swings, raging, and periods of hypersexuality all controlled by medications, and his learning disabilities discovered and treated by the school professionals and tutors, the mother hadn’t realized he was still suffering with more than his fair share of anxiety.

Indeed, there is a surprisingly robust scientific literature that documents the frequent co-morbidity or association between bipolar disorder and a number of anxiety disorders, but this association is frequently overlooked when a differential diagnosis is made. Instead, anxiety disorders are often seen as diagnoses existing all by themselves--divorced from the possibility of a co-existing mood disorder. Thus, a child frequently receives a diagnosis of generalized anxiety disorder—GAD—or an adolescent frequently gets the diagnosis of panic disorder, and the anxiety disorders are not viewed as a possible pre-cursor to a mood disorder or as a possibly co-occurring condition.

In cases where the bipolar disorder is recognized, the primary focus of treatment becomes the stabilizing of the moods and the modulation of the aggression, and the evaluation of residual anxiety is not high on the list of priorities. In many situations, anxiety is viewed as the least of the problem—more of a benign condition-- and not the pernicious one that eats away at a child’s feeling of safety and self-esteem. Dr. Ira Glovinsky co-author of Bipolar Patterns in Children told us that he works with children who describe anxiety as “a tornado inside my body that my body just can’t hold inside.”; and “It’s bigger than my body and it seeps out the side seams.” Dr. Glovinsky added: “Many of these children are just hemorrhaging anxiety. When one thinks about it, it is easy to see how chronic anxiety would contribute to irritability, lack of concentration, and hyperactivity.”

Therefore, we thought it might be a good idea to focus this issue on this common co-occurrence of mood disorders and the anxiety disorders.

How Does the DSM-IV Define Anxiety Disorders?

The DSM-IV devotes 51 pages to the anxiety disorders which, if we leave aside anxiety induced by substances or by a general medical condition, broadly includes:

• Panic Attack
• Agoraphobia
• Specific Phobia
• Social Phobia
• Obsessive –Compulsive Disorder
• Posttraumatic Stress Disorder
• Acute Stress Disorder
• Generalized Anxiety Disorder

Separation anxiety, so commonly seen in children with bipolar disorder, is not listed with the anxiety disorders but under the category “Disorders Usually First Diagnosed in Infancy, Childhood, or Adolescence.”

What Does the Scientific Literature Conclude About the Interface of Anxiety Disorders and Mood Disorders?

There is no dearth of good studies linking mood disorders and anxiety disorders. In 1995, Peter Lewinsohn and colleagues, in a community study of high school students with any form of anxiety disorder, reported that anxious youths were seven times more likely to have comorbid bipolar disorder than students without any anxiety disorder.

Panic disorder represents one of the most extreme manifestations of anxiety in both adults and children. The association between both panic attacks and panic disorder and major depression has been well documented. In addition, in adults, panic disorder has been shown to be associated with bipolar disorder, with 13-to-23% of adults with panic disorder having a comorbid bipolar disorder. Conversely, in adults with bipolar disorder, the lifetime rates of comorbid panic disorder range from 36-to-80%.

The association between anxiety disorders and bipolar disorder is “particularly marked in pediatric samples,” says Dr. Janet Wozniak, assistant professor of psychiatry at Harvard Medical School. She notes that “studies of children and adolescents with bipolar disorder report that 56% of these children have multiple anxiety disorders.” Dr. Joseph Biederman, also of Harvard Medical School, found that 52% of the children diagnosed with panic disorder in his study had a co-occurrring bipolar disorder.

Dr. Boris Birmaher of Western Psychiatric Institute and Clinic at the University of Pittsburgh School of Medicine published a paper in the Journal of Clinical Psychiatry entitled: “Is Bipolar Disorder Specifically Associated with Panic Disorder in Youths?” It was a large study of 2025 youths aged 5-19, and patients were grouped into those with panic disorder (N=42); those with non-panic disorder anxiety disorders (N=407); and psychiatric controls with no anxiety disorders (N=1576).

The results of this study showed that youths with panic disorder were more likely to exhibit co-morbid bipolar disorder (N=8; 19%) than youths with either non-panic disorder anxiety disorders (N=22, 5.4%) or non-anxious psychiatric disorders (N=112, 7.1%). The conclusions reached by the investigators were that “The presence of either panic disorder or bipolar disorder in youths made the co-occurrence of the other condition more likely, as has been noted in adults.”

Actress Patty Duke, who was diagnosed with manic-depression years after her illness began recalls “a fear of death so powerful it precipitated anxiety attacks from the early 1950s to 1983. I was obsessed, truly obsessed with my mortality. All of a sudden the absolute realization of my mortality would hit and I just felt impelled to scream. Sometimes it was what I’d call a bloody-murder scream, sometimes words like ‘No! No! No! No!’ Inevitably though, it happened at night, on the way to sleep. I’d scream every night of my life. I was overtaken by abject terror.”

Dr. Birmaher and his collegues wonder in their article referenced above if children and adolescents with panic disorder are at higher risk for the development of a bipolar disorder, but state that no such prospective studies have been done yet. They do, however warn that if it turns out that panic disorder is a marker for bipolar disorder, then before patients with panic disorder are treated with antidepressants, “a personal and family history should be elicited, and they should be closely monitored for the emergence of mania.”

They then go on to state:

Because children with panic disorder often have somatic complaints such as shortness of breath or chest pain, they often present first to primary care or specialty physicians. When treating patients who present in the primary care sector, the challenge is two-fold: making the diagnosis and, if pharmacotherapy is initiated, carefully monitoring for the onset of manic symptoms. Therefore, any physician who makes a diagnosis of panic disorder must make a conscious effort to rule out bipolar disorder before medication is initiated or risk exacerbating a “hidden” manic/hypomanic state.

In other words, if a bipolar disorder is co-occurring, it could be worsened by the medical treatment used for panic or anxiety disorder, specifically the SSRIs such as Paxil and Zoloft. (We will discuss the treatment of panic disorders and other anxiety disorders toward the end of this newsletter.)

A Closer look at Some of the Anxiety Disorders

SEPARATION ANXIETY

Many mothers have described their children’s inability to be separated from them—in the early days of infanthood, and well beyond. One mother told us she called her child “the Velcro Kid.” Others remember “cleaning chicken with her in a Snugli”; “vacuuming with her in a sling”; and another mother described being “mauled with his nails scraping down my chest as he struggled against being withdrawn by his father, who was trying to take him from me so that I could take a shower.”

A mother from Illinois emailed us about the separation anxiety her son was experiencing and had this to say:

Right now Jamison can’t be separated from me—it’s like the umbilical cord grew back! I can’t get him out of my room at night. If he falls asleep anywhere else, he ends up there eventually. I’ve stepped on him in the middle of the night many times. He hides under the bed with only his head sticking out. But he gets so anxious, and this relieves some of it.

How Does Separation Anxiety Affect the Child and Family Members?

In almost all instances, the mother is most affected by the child’s powerful attachment demands; but as the child’s exclusive desire for her companionship begins to rule the roost, others in the family will also be affected. Some fathers may be entirely excluded from this intense relationship and viewed by the children as intruders. Mothers who remain identified with the role of satisfying the child’s needs are easily drawn into perpetual motherhood. They too find it hard to separate, particularly if they have inherited a bipolar disorder or temperament, and their own fears of separation and abandonment fuse with those of the child.

There are no formulas for dealing with these particular problems, but it is abundantly clear that managing the separation anxiety in the child and becoming aware of its effects on the family should become a primary therapeutic goal of the treatment of the condition.

Crucial is helping the child who experiences this level of fear and terror to understand that the sense of imminent loss of control (by becoming isolated from the mother) is not based on reality. The parents and therapists need to help the verbal child to grasp the range and intensity of his feelings—anxiety and anger as well as elation and depression—and to express these feelings openly on a regular basis. Any exercise that helps a child to label feelings and talk about them in play gives order, definition, and a feeling of self-control that would counter the prevailing tendency to believe that feelings are overwhelming and unmanageable—a tendency likely to impede emotional growth and maturation.

OBSESSIVE-COMPULSIVE DISORDER (OCD)

A study by Daniel Geller that focused on 217 children with obsessive-compulsive disorder at the McLean Hospital/Massachusetts Pediatric OCD clinic, found that a full 69 percent of the study sample also carried diagnoses of mood disorders. The Epidemiological Catchment Area database supports the conclusion that the lifetime rate of comorbidity for obsessive-compulsive disorder is particularly high among bipolar subjects.

Children with OCD have recurrent and intrusive thoughts of impending harm that can be allayed only by some compulsive act. They feel compelled to perform repetitive acts or rituals to ward off the discomfort and anxiety they experience, but these acts can cause the child shame and embarrassment as well as make it hard to get out of the house and go about a typical kid’s day.

Some examples of repetitive acts or rituals designed to reduce the anxiety and keep a dreaded event from occurring include: placing objects just right; touching things a self-specified number of times; checking behaviors….Some children count or repeat phrases over and over; other children compulsively pick at their skin.

Many children describe obsessions about dirt or contamination, and children as well as adults describe handwashing or showering rituals in which they wash their hands over 80 times a day or spend hours attempting to shower themselves clean. Many children explain that they don’t know why they do these rituals—they know they are senseless. Still, they feel a sense of pressure, and the action partially relieves the anxiety.

Demitri F. Papolos, M.D. and Steven Tresker recently examined ratings on the Child Yale Brown Obsessive Compulsive Scale (YBOCS) for 229 children diagnosed with bipolar disorder. They divided the sample into groups stratified by frequency of symptoms and when they looked at the group that had 14-or-more positively-endorsed symptoms, they found that the most prevalent symptoms were hoarding obsessions, fears of contamination, and fear of or attraction to violent or horrific images. In light of the fact that one of the cardinal features of juvenile-onset bipolar disorder is difficulty moderating aggressive impulses, specific fears and rituals associated with the control of those aggressive impulses should not be surprising.

A mother from Oregon sent us an email that sadly detailed her daughter’s anxiety about her aggressive impulses:

Cally was very afraid to make wishes when she was little. Blowing out candles on a birthday cake was horrible for her because she was afraid that right at the last minute she would wish for something bad to happen to someone and it would come true. She was/is afraid to wish on stars in the sky for the same reason.

POSTTRAUMATIC STRESS DISORDER

Many children with bipolar disorder have a pronounced sensory sensitivity. These children are easily aroused from birth and overreact to environmental stimulation and their own internal body intensities. They also seem susceptible to horrific night terrors or other arousal disorders of sleep, which may possibly have a significant influence on their perception and behavior and the development of social repertoire. One can’t help wondering if the death, dismemberment and gory content of their dreams and night terrors don’t traumatize these children also. These nighttime agonies may make them extremely sensitive to any negative experiences witnessed in life, and a vicious cycle may develop.

Because of this extreme sensitivity to internal intrapsychic and bodily experience as well as environmental stimuli, the impact of stressful events (whether they be a form of vivid, persistent night terrors) or anger directed at them, or early loss, these children have the potential to be easily traumatized, and therefore it should be no surprise that both children and adults with a bipolar vulnerability often have symptoms or diagnoses of posttraumatic stress disorder.

According to the DSM-IV, “The essential feature of Posttraumatic Stress Disorder is the development of characteristic symptoms following exposure to an extreme traumatic stressor involving direct personal experience of an event that involves actual or threatened death or serious injury, or other threat to one’s physical integrity; or witnessing an event that involves actual death, injury, or a threat to the physical integrity of another person.” The “D” criteria of PTSD reads:

Persistent symptoms of increased arousal (not present before the trauma) as indicated by two or more of the following:

1. difficulty falling or staying asleep.
2. irritability or outbursts of anger
3. difficulty concentrating
4. hypervigilance
5. exaggerated startle response

As one mother wrote about her 11-year-old son:

My son’s anxiety is manifested in always seeing the most negative outcome for any situation that begins to turn even slightly in his disfavor. He is also fearful about being kidnapped and becomes anxious in public when he thinks someone might be following us or looks suspicious to him. I think he is still recovering from my being mugged three years ago in broad daylight in his presence. But he was anxious before that too. It is hard for him to fall asleep because negative thoughts pile into his head at that time.

Dr. Janet Wozniak wrote and told us of a study that she and her colleagues conducted focusing on PTSD using a longitudinal sample of ADHD boys (about 20% of this sample had comorbid bipolar disorder). They found that bipolar disorder generally pre-dated PTSD, when PTSD occurred. “This is important because many clinicians erroneously attribute the mood symptoms of bipolar disorder to having experienced a trauma, when in fact the mood symptoms were present prior to the trauma,” says Dr. Wozniak.

This finding is also important because—as we indicated earlier—it may be the case that children with bipolar disorder are at particular risk for traumatic experience.

What Biological Underpinnings May Explain the Association Between Bipolar Disorder and Anxiety Disorders?

It has long been recognized that an excess of stressful life events is associated with the onset and relapse of major depression and bipolar illness in adult patients. Prospective studies of children at risk for the development of mood disorders suggest that they are born with an enhanced genetic susceptibility to develop anxiety and depression. These children appear to have a low threshold for anxiety and are over-reactive to stressful events (real or perceived) such as deprivation, loss, rejection, and humiliation. (This may be why these children so over-react to the simple word “No,” which in its expression contains elements of deprivation, loss, rejection, and humiliation.)

CRF and the Much-Talked-About GRK3 Gene

CRF is the neuropeptide in the brain that participates in the generation of the stress response. It also has important influences on the systems that regulate arousal, sleep/wake transitions, appetite, energy production, and the experience of pleasure and pain.

GRK3—a G-protein-coupled-receptor kinase plays an important role in the regulation of CRF receptors by turning them off at a certain point after they have been stimulated.

We spoke with Dr. Richard Hauger, professor of psychiatry at the University of California San Diego and a leading author of the recently reported study: “Evidence that a single nucleotide polymorphism in the promoter of the G protein receptor kinase 3 gene is associated with bipolar disorder,” and he explained:

We hypothesize that activation of brain neural networks by CRF during stress may require rapid counterregulation by the GRK3-mediated mechanism.

It has been established that exposure to severe stress can induce a long-term sensitization to anxiety-inducing stimuli. Therefore, a deficiency in GRK3 expression (caused by a different sequence of nucleotides that makes the promotor gene less capable of promoting transcription of the protein) may render brain CRF receptors incapable of being turned off when chronically exposed to high levels of CRF. This excessive degree of CRF receptor activation could contribute to the development of anxiety and depression.

The Treatment of Children and Adolescents With Anxiety Disorders

In some cases, the anxiety disorders, whether they be generalized anxiety, panic disorder, or obsessive-compulsive disorder, disappear with proper mood stabilization using lithium or one of the anticonvulsants. Of particular interest, however, is a study published in the March 2003 issue of the Journal of Clinical Psychiatry which looked at 318 adult bipolar patients in France and found that “Bipolar patients with anxiety responded less well to anticonvulsant drugs than did bipolar subjects without anxiety disorder, whereas the efficacy of lithium was similar in both groups.” In other words, the patients who were bipolar and suffered with anxiety disorders responded better to lithium than to the anticonvulsants.

This was the first study to show that bipolar patients with anxiety disorders may have a poorer response to long-term treatment, depending on the type of mood stabilizer given. However, this would have to be replicated in a larger group of patients, with randomization, and it would have to be specifically looked at in children and adolescents.

We asked Dr. Janet Wozniak from the Harvard Medical School some questions about the treatment of bipolar disorder and anxiety in youngsters and she replied:

In the cases of pediatric bipolar disorder, our rule of thumb is to stabilize the manic mood prior to addressing issues of comorbidity with depression, ADHD and anxiety. Sometimes when the manic mood state is treated the anxiety symptoms also improve. Sometimes the opposite is observed: after the mood is stabilized the anxiety “comes front and center”. We have no way of predicting who will fall in which category. But the idea that mood stabilizers "cause" anxiety may be erroneous. It may be that the comorbid anxiety is more obvious when the mood is stabilized, given that reports suggest anxiety occurs comorbidly with bpd in many adults, children and adolescents.

There are no studies to inform us which agents are best to use when we add an anti-anxiety agent for this population. In practice, we make use of all the possible treatments including Gabatril, Neurontin (which may be less likely to destabilize mood or in some small number of cases might help mood), benzodiazepines (which unfortunately could be sedating, cognitively clouding, or have a paradoxical effect), buspirone, and antidepressants (which of course carry the risk of exacerbating mania).

Neurontin and Gabitril (two anticonvulsant drugs) both increase the neurotransmitter GABA transynaptically, which is where benzodiazepines such as Klonopin and Ativan work against anxiety.

New Medications in the Pipeline

New types of medications that target the CRF receptors are looking good as anti-anxiety medications in early clinical trials, and may be on the market in the next year or two. Dr. Hauger also told us:

Clinical trials are currently underway to test the efficacy of selective CRF1 receptor antagonists in the treatment of major depression and anxiety disorders. Preliminary data revealed that the small molecule CRF1 receptor antagonist R121919 (NBI30775) developed by Neurocrine Biosciences Inc. significantly lowered anxiety and depression scores in patients with major depression. The development of CRF1 receptor antagonist pharmacotherapy rests on the assumption that presynaptic hypersecretion of CRF is solely responsible for the hyper-stimulation of CRF systems observed during episodes of major depression. However, it may also be important to enhance GRK-mediated CRF1 receptor desensitization in patients with major depression and anxiety disorders.

We have heard that other pharmaceutical companies are also bringing a CRF receptor antagonist onto the market sometime in the near future.

Although we know of no studies looking specifically at anxiety disorders and bipolar disorder treated with cognitive therapy, clinicians who have used it have told us that it does indeed help. Some psychologists have suggested that the book, Brain Lock by UCLA psychiatrist, Jeffrey Schwartz, is helpful with obsessive-compulsive symptoms. It’s four-step method of Relabeling, Reattributing, Refocusing, and Revaluing may make a difference for older children and adolescents.

In Conclusion

From all of the above, it is clear that children with bipolar disorder are pre-disposed to and suffer unduly from anxiety disorders (often more than one in their lifetime) and that this frequent comorbidity should be taken into consideration when a diagnosis is made so that the bipolar disorder is not missed and exacerbated by the wrong selection of medication, and so that the child who is recognized as having bipolar disorder is not left in an uncomfortable state as the mood becomes stabilized (if anxiety should become an issue).

It is obvious that much needs to be learned about the strong undisputable association between the anxiety disorders and bipolar disorder and that clinicians and researchers need to devote time and energy to this co-morbidity. The good news is that new discoveries in the field of molecular genetics are certain to bring greater understanding and better treatments.

* * * *

Despite the springtime weeks (and weeks) of rain, we wish you sunny summer days, and balmy summer nights.

As always, we look forward to hearing from you.

Janice Papolos and Demitri Papolos, M.D.

In Loving Memory of Beatrice Franz Cohen
(December 19, 1919 - May 23, 2003)

The authors wish to thank Cheryll Hart, Adrienne Robins, and Drs. Janet Wozniak, Ira Glovinsky, and Richard Hauger

Bibliography:

American Psychiatric Association. Diagnostic and statistical manual of mental disorders (4th Edition). Washington, D.C: 1994.

Barrett, TB, Hauger, RL, et al. “Evidence that a single nucleotide polymorphism in the promotor of the G protein receptor kinase 3 gene is associated with bipolar disorder." Molecular Psychiatry 2003; 8:546-557.

Biederman, J, Farrone, SV., et al. “Panic Disorder and agoraphobia in consecutively referred children and adolescents.” Journal of the American Academy of Child and Adolescent Psychiatry 1997;36: 214-223.

Birmaher, Boris, Kennah, Adam, Brent, David et al. “Is bipolar disorder specifically associated with panic disorder in youths?” Journal of Clinical Psychiatry 2002;63: 414-419.

Chen, Yian-Who, and Steven C. Dilsaver. “Comorbidity of panic disorder in bipolar illness: Evidence from the epidemiologic catchement area survey.” American Journal of Psychiatry 1995; 152:280-282.

Dautzenberg, Frank M., and Richard L. Hauger. “The CRF peptide family and their receptors: yet more partners discovered.” Trends in Pharmacological Sciences 2002;23: 71-77.

Duke, Patty. Call Me Anna. New York: Bantam Books, 1990.

Glovinsky, Ira. Personal communication June 12, 2003.

Gorman, Jack M. “New molecular targets for antianxiety interventions.” Journal of Clinical Psychiatry 2003; 64 (suppl 3): 28-35.

Hauger, Richard L. E-mail correspondence of June 16th and 21. Telephone conversation of June 21.

Henry, Chantel, Van den Bulke, Donatienne, Bellivier, Frank. “Anxiety disorders in 318 bipolar patients: prevalence and impact on illness severity and response to mood stabilizer.” Journal of Clinical Psychiatry 2003; 64: 331-335.

Lewinsohn, PM, Klein, DN, Seeley JR. “Bipolar disorder in community sample of older adolescents: prevalence, phenomenology, comorbidity and course.” Journal of the American Academy of Child and Adolescent Psychiatry 1995; 15: 219-226.

Johnson, JG, Cohen, P, and Brook JS. “Associations between bipolar disorder and other psychiatric disorders during adolescence and early adulthood: A community-based longitudinal investigation. American Journal of Psychiatry 2000; 157: 1679-1681.

Masi, Gabriele, Toni, Christina, Purugi, Guilio, et al. “Anxiety disorders in
children and adolescents: a neglected comorbidity.” Canadian
Journal of Psychiatry 2001; 46: 797-802.

Papolos, Demitri F., and Steven Tresker.”Assessment of obsessive-compulsive Behavior in childhood-onset bipolar disorder using the Yale-Brown Obsessive-compulsive scale.” (submitted)

Papolos, Demitri. “Bipolar disorder and comorbid disorders: The case for a dimensional nosology.” In Bipolar Disorder in Childhood and Early Adolescence by Barbara Geller and Melissa P. Delbello, editors. New York: Guilford Press, 2003.

Schwartz, Jeffrey M. with Beverly Beyette. Brain Lock: Free Yourself from Obsessive- Compulsive Behavior. New York: HarperCollins, 1997.

Wozniak, Janet, Biederman, Joseph, et al. “A pilot family study of childhood- onset mania. Journal of the American Academy of Child and Adolescent Psychiatry 1995;34: 1577-1583.

Wozniak, Janet, Joseph Biederman, et al. “Parsing the comorbidity between bipolar disorder and anxiety disorders: A familial risk analysis.” Journal of Child and Adolescent Psychopharmacology 2002;12: 101-111.

Wozniak, J, Crawford MH, Biederman J, Faraone SV, et al. Antecedents and complications of trauma in boys with ADHD: findings from a longitudinal study. Journal of the American Academy of Child and Adolescent Psychiaty 1999 Jan;38(1):48-55.

Wozniak, Janet. E-mail correspondence of June 20 and July 3, 2003.

Three years ago, we published the first issue of The Bipolar Child Newsletter, and in the opening paragraph we outlined what we hoped to accomplish: We wrote: "We thought an e-mail newsletter would be a good forum in which to keep parents, educators, and mental health professionals abreast of the newest findings in the fields of psychopharmacology, genetics, and neurobiology as they relate to early-onset bipolar disorder.";

In keeping with that aim we'd like to focus this issue on a newly available, novel, antipsychotic medicine, aripiprazole (ari-PIP-prazole; brand name Abilify). Psychiatrists are starting to prescribe it, parents are writing to us asking for information about it, and early, anecdotal reports are promising. Much remains to be learned about this unusual new drug. Very little is known about its potential clinical utility and relative tolerability in children suffering with early-onset bipolar disorder, and scientific studies of that application are only now beginning. Still, the drug's unique properties and apparently excellent tolerability in adults offer a great deal of hope.

Let us spell out what we know about Abilify in February 2003.

Aripiprazole was discovered in Japan by Otsuka Phramaceutical Co., Ltd. The compound entered Phase II trials for patients with schizophrenia in that country by 1995, followed by Phase III trials in Europe by 2000. In 1999, Otsuka-America arranged with Bristol-Myers Squibb to manage Phase III clinical trials and marketing of the new drug in the US. Abilify received FDA approval in November of 2002. It is so new that clinical experience with it, particularly in children, remains very limited.

The Mechanism of Action

Aripiprazole is chemically different from other atypical antipsychotic agents and is also believed to have unique pharmacological actions that are different from other atypical antipsychotic drugs, including clopazine (Clozaril), olanzapine (Zypexa), or quetiapine (Seroquel), risperidone (Risperdal), or ziprasidone (Geodon). Aripiprazole acts as a weak stimulator (so-called "partial"; agonist) at dopamine D2 receptors, with the potential for exerting either antagonistic (inhibitory) or agonistic (stimulating) effects, depending on the sensitivity of the receptors and availability of dopamine, its natural agonist in the brain. Aripiprazole also has similar actions at serotonin 5-HT1A receptors, as well as acting as an antagonist at serotonin 5-HT2A receptors, and having a number of other lesser actions.

In simple terms, partial agonism refers to the ability of a drug to block a receptor if it is overstimulated or in competition with a natural agonist, such as dopamine and serotonin themselves, but also to stimulate a receptor when the natural agonist is unavailable. These unprecedented properties in a clinically effective antipsychotic agent indicate that Abilify can be considered a "next-generation"; atypical antipsychotic.

Aripiprazole is the first dopamine partial-agonist approved in the US for clinical use in adult patients with schizophrenia, although other dopamine partial-agonsists (e.g., bromocriptine [Parlodel] and pramipexole [Mirapex]) have been used to treat Parkinson's disease for many years. Aripiprazole is effective in reducing both the positive and negative symptoms of schizophrenia, and is well tolerated by most patients. In addition, promising research studies have been conducted with adults suffering with bipolar disorder. A multi-center, double-blind randomized, placebo-controlled trial included 262 adult patients diagnosed with acute mania or mixed manic-depressive states. By day four of treatment, aripiprazole was significantly better than placebo in reducing acute manic symptoms, including elevated mood, irritability, disturbed thinking, and disruptive-aggressive behavior.

These findings have prompted adult and child psychiatrists to begin to prescribe Abilify for both indicated and off-label applications, including for early-onset bipolar disorder in children and adolescents.

Advantages of Abilify

Like other atypical antipsychotics, aripiprazole has a low risk of producing extrapyramidal symptoms (EPS)—the disorders of posture and movement that some patients experience with the older neuroleptic-type antipsychotics, such as chlorpromazine (Thorazine) and haloperidal (Haldol). Typical EPS include early and later muscle contractions (dystonia), slowed movements (akinesia, or parkinsonism), motor restlessness often accompanied by severe anxiety (akathisia), and later-emerging tardive dyskinesia (TD).

In our newsletter of Fall 2000, we first sounded some concerns about a series of general medical or metabolic problems that were being increasingly reported in association with the atypical antipsychotic medications such as Clozaril, Zyprexa, Risperdal, and Seroquel. These include new-onset, type II (non-insulin dependent) diabetes mellitus, changes in lipid metabolism and blood concentrations, sometimes severe and persistent elevation of prolactin and other hormonal imbalances (milk oozes from children's nipples), and a range of adverse cardiovascular effects that include low blood pressure and abnormal functioning of the heart. The long-term implications of such adverse effects are not known, particularly for youngsters who may require such medications for decades.

Studies conducted with Abilify show that patients gain little if any weight; and the drug seems to cause no changes in the plasma glucose levels that might suggest risk of diabetes. Nor does it seem to increase serum cholesterol or other lipids. Also, the drug does not increase prolactin levels, and in fact appears to decrease them to normal levels, and there have been no reports of heart rhythm abnormalities (such as a prolonging of the electrical recovery time of the heart [QTc interval] in the electrocardiogram), hematological changes, serum chemistry changes, or thyroid problems.

Parents who wrote to us asked if there were any cases of tardive dyskinesia (TD), the late appearing movement disorder that can present with involuntary facial grimacing, lip-smacking, chewing and sucking movements, cheek puffing, and worm-like movements of the tongue, as well as quick movements of the fingers, toes, arms and legs, or dystonic, writhing postures. At this point there have been no reports, but it will be years before anyone can answer this question with any authority.

The other question we were asked was: "Does this med punk out like some of the others and will the doctor have to keep increasing the dose?"; Again, we have few answers, but the clinical trials involving patients with schizophrenia showed that Abilify sustained improvements in the positive, negative, and depressive symptoms of schizophrenia for at least a year.

The drug has been evaluated for safety in at least 5,592 adult patients who participated in multiple-dose, premarketing trials in schizophrenia, bipolar mania, and dementia of the Alzheimer's type, for a total of approximately 3,639 patient-years of exposure. A total of 1,887 aripiprazole-treated patients were treated for at least six months, and 1,251 for at least a year.

Promising--so far, but what are the side effects and how effective is it for children struggling with the symptoms of bipolar disorder?

The Side Effects

The most common adverse effects reported among adult bipolar disorder patients, specifically, included headache (32%), nausea (14%), vomiting (12%), constipation (10%), anxiety (25%), insomnia (24%), dizziness (11%), and akathisia (10%). Sleepiness was found with higher doses. Placebo-treated patients in the same study also suffered side effects such as headache, agitation, nausea, indigestion, and anxiety. Few of the side effects for either group lasted beyond the first week.

Although many patients report few side effects with the medication, in children, specifically, we have heard of single cases: one very young child was taken off the drug due to severe constipation, one 12-year-old had new mania, and one youngster had a dystonic reaction—one of the movement disorders we spoke of above (dystonic reactions can be quickly counteracted by antihistamines such as diphenhydramine [Benadryl], or by anticholinergic drugs such as benztropine [Cogentin] or trihexyphenidyl [Artane]).

Dr. Raymond Behr, a highly respected child psychiatrist on the faculty of the Albert Einstein College of Medicine and founder of the Child Psychopharmacology Listserv for child psychiatrists is very impressed with Abilify, but has reported five cases of akathisia (out of the first 34 patients for whom he has prescribed the medication). He explained that this was not "agitation,"; but "real akathisia."; While the risk of EPS is much lower than with the older neuroleptic agents, akathisia probably has a different basis than other movement disorders associated with antipsychotic drugs, and can occur occasionally even with atypical agents. Parents should be aware of akathisia and be alert to it.

According to Ross J. Baldessarini, M.D. of Harvard Medical School, and one of the leading authorities on antipsychotic medications:

Akathisia is motor restlessness that can occur with all antipsychotics, typical or atypical, but is more likely to occur with the older typical agents and D2 blocking agents. It can occur occasionally and in subtle fashion even with clozapine. Akathisia involves extreme subjective distress with a kind of "anxiety"; that involves a physical sense of discomfort, often referred to the legs, and partially relieved by moving around, hence the restless component. Sometimes it can be treated with propranolol (Inderal) or benzodiazepines, but it may require removing the offending agent.

He added: "This common condition is often overlooked or misunderstood or mislabled as ‘agitation' and it has been associated with aggressive or even suicidal behavior.";

Since so many children with bipolar disorder suffer paradoxical reactions to all drugs (even those thought to quell mania) the hypothetical risk of inducing or worsening mania or psychosis by a dopamine partial-agonist still remains a concern for us and many clinicians, and its clarification awaits more clinical experience.

Reports from the Medical Front

Dr. Raymond Behr told us that "I have used Abilify in several kids and many of the responses have been dramatically positive. My impression is that, if it is going to work, there usually is a very quick response --within a few days. It is very similar to the effect that one sees with Zyprexa (olanzapine) but without the sedation and weight gain.";

We corresponded extensively with Mani N. Pavuluri, M.D. the director of the Pediatric Mood Disorders Clinic at the Institute of Juvenile Research at the University of Illinois at Chicago. In one e-mail, she told us of a five- year-old child with bipolar disorder who was severely psychotic, suffering delusions of reference, raging, and refractory to three previous trials of mood stabilizers and two antipsychotics. The child is now doing well on 5 mg of Abilify a day. (A four-year-old patient, however, could not tolerate the drug due to constipation.)

Because Dr. Pavuluri and her colleagues were so impressed with their observations of the effects of aripiprazole in difficult-to-treat children who have bipolar disorder (and the results of the five clinical trials that were completed at their center in adults) they have designed a research protocol that proposes to examine Abilify in 7-17 year-olds with bipolar disorder over a six-week period.

David Cremer, M.D. a psychiatrist from Miami, Florida informed his collegues on the Professional Listserv of the Juvenile Bipolar Research Foundation: "I have two young patients who are bipolar and who have been on every medication for therapeutic trials and were refractory, or who stopped medications due to side effects, and they are both doing well on Abilify.";

When we contacted him and asked for some more details, he described one of his children thus:

The first patient, KM, is seven-years-old and his core symptoms were rages, sleeplessness, irritability with remorse, low frustration tolerance, fickle changes in mood, rapid speech, and an ADHD profile.

He was refractory to every medication (all the anticonvulsants), he was briefly responsive to the atypical antipsychotics and briefly responsive to lithium. On Abilify he has been able to engage in play in the office and used the time to discuss some of his feelings about how he has been feeling. The ADHD-type picture has abated with the medication.

Dr. Cremer then wrote about his other patient, a nine-and-a-half-year-old boy:

TF has severe separation anxiety, fickle moods, bursts of hyperactivity, some bizarre behavior, moodiness, and spells of rages with pressured speech. He has responded to an atypical antipsychotic, but with the side effects of puffiness and weight gain. He is on carbamazepine without side effects.

Since starting him on Abilify, he lost his puffiness almost immediately and is losing weight. His temper has stabilized. He still has his moments, but they are within the realm of average for his social delay.

Dr. Cremer mentioned that both of these children showed improvement on their mental status exams.

Reports from the Home Front

How are the children doing on Abilify—at home and in school? Several parents wrote to us and again, the stories were positive (but please bear in mind that the negative stories have not reached us yet, and that all children will not have these superb reactions or be able to tolerate the drug). One mother said:

Since Peter started the drug, things have been so much better. He is on 10mg and the first few days he was in a major "fog"; and slept a lot, and had an upset tummy. I thought we were going to have to lower the dose but waited it out and things did get better and the sleepiness went away and he no longer walks around in a fog. Things are starting to "click"; in his head as far as school work is concerned. His upsets are not rages anymore. And the constant fighting with siblings......well, now it is just regular sibling rivalry that we have never gotten to see before. He is much more compliant and his aggression level has gone way, way down. He gets up in the morning and says: "Good morning"; instead of "I hate you!"; Not sure how long it will last, but I am enjoying it very much!

She added something that reminded us once again what this illness does not only to the child, but to the entire family, and especially the siblings: She said: "His little brother is still having a hard time understanding why Peter is being nice and not his usual self that he was used to. But we are working on that.";

We've been corresponding with the grandfather of a young boy for some time now and he wrote recently to tell us of his grandson's reactions to Abilify. He said:

His daily reports from school are all positive, and both his special-ed teachers are now able to concentrate on his education instead of his behavior. I notice there is no more cycling and no more rages. He is more calm; and when things go wrong, he doesn't explode as he did in the past. As a result of the Abilify, he is a happier 9-year old, and I no longer walk on egg shells when he is with me.

Another mother described her fourth-grader's reaction to the medication thus:

He began the Abilify and on the third to fourth day, we saw dramatic improvement. It was almost as if we were dealing with a different child. The rages stopped. He has always been an affectionate child, but now his affection shines through clearly. He's been getting wonderful reports from his special- ed teachers at school. I still find myself preparing for battle when I have to reprimand him, but I'm pleasantly surprised when he complies with my requests now and there is no problem. This medication has been truly amazing for my son and our family.

And because there is no such thing as too much good news to parents of children suffering with bipolar disorder, we conclude with this mother's description:

While it hasn't solved all of our son's problems, it has controlled his paranoia and mania, decreased his grandiosity (but not eliminated it), made it possible for him to read and focus better, and has done all of this without major side effects (once we got up to 15 mg and eliminated the other antipsychotic medications completely). He tells me that he feels much better able to control himself. He says that he can now read without his mind wandering off in different directions. He can also let negative issues drop, rather than dwelling on them.

She continued:

We have noticed a big change in him. He gets up in the morning and stays awake and alert all day (no sedation). He is generally more cooperative and although he still does annoying things, I can now confront him without feeling like I need the National Guard to back me up. His pediatrician, his therapist, and teachers at school have all noticed the change for the better.

There is something intriguing in this story and in Dr. Cremer's reports above. The children's focus and attention seem to have improved on Abilify. Indeed, Dr. Mani Pavuluri proposes to look at the drug's ability to improve cognitive functioning in her study patients. The results should be interesting for all in the field, and for all parents and educators.

Dosing

Abilify is supplied in 10, 15, 20, and 30 mg tablets--a disadvantage for children, who are typically started on lower doses. Parents can cut tablets into halves or even quarters, or bear extra costs in using the services of compounding pharmacies. We understand from Bristol-Myers Squibb that lower milligram formulations as well as a liquid formulation will be available some time "in the foreseeable future,"; but we can't be any more specific than that.

Typical adult doses for the treatment of psychotic disorders are 10-15 mg/day, with an overall range of 5-30 mg. Doses for children are not established yet, but are likely to be about half those used for adults. Moreover, the specific use of this drug to treat psychotic patients under age 18, or for those diagnosed with bipolar disorder is not approved by the FDA, though it is evidently starting to be used clinically on an off-label basis in adolescents and children and for bipolar disorder patients.

Dr. Pavuluri reports that she starts youngsters weighing less than 110 pounds at 2.5 mg, and those over 110 pounds at 5 mg initially to avoid nausea, and doubles the dose within a week if it is tolerated. Further dose increases usually are not made for another week or two as steady state, or stable, tissue concentrations are achieved.

It is a good idea to give the medication in the morning, with a meal or some food in order to minimize risk of nausea and insomnia, which are among its most common side effects. Also, parents should ensure that the child eats fruit and vegetables, or high-fiber cereals, and drinks plenty of fluids in order to prevent constipation.

Drug-to-Drug Interactions

The anticonvulsant mood stabilizer, carbamazepine (Tegretol), induces CYP3A4 and 2D6 liver enzymes which can increase the ability of the body to remove Abilify, and so decrease Abilify's concentration in the blood. The manufacturer recommends that the dosage of Abilify be doubled as long as both drugs are taken at the same time. This consideration brings up the question as to whether Trileptal (oxcarbazepine, an analogue of carbamazepine) can cause this same increase in clearance as Trileptal also has some effect on the liver enzyme CYP3A4 that normally removes Abilify. The possibility seems to exist, but no one has a definitive answer about this yet and careful dosing ad an attentive eye to the clinical picture will be required.

Antidepressants such as fluoxetine (Prozac) fluvoxamine (Luvox) and paroxetine (Paxil) can slow the body's ability to eliminate Abilify by inhibiting CYP3A4 and CYP2D6 liver enzymes, and so increasing blood levels of the drug. When any of these SSRIs are prescribed with Abilify, the manufacturer recommends that the Abilify be reduced at least to one-half of its current or usual dose.

Again, physicians who have patients on either class of these medications will have to monitor the clinical picture carefully and make adjustments as needed.

The Cost of the Medication

Abilify is very expensive. A Connecticut retail pharmacy quoted the following prices for 30 tablets at each of three dosages: 10-mg or 15-mg, $357, and 20-mg, $506. (We have seen cheaper prices so it behooves all parents to shop around.)

For families who don't have prescription cards or the funds to pay for Abilify, Bristol-Myers Squibb moved quickly to set up a Patient Assistance Program at 1-800-332-2056.

Conclusions

Because early anecdotal reports from researchers, clinicians, and parents seem so positive, and because the drug's safety profile has been very promising to date (and it doesn't confound a child's problems with weight gain), it is hard not to be hopeful about this new medicine. However, it is important to state again that Abilify is only beginning to be studied in children, and a more balanced picture is certain to evolve as data accumulates. (A study is currently enrolling at the NIMH comparing risperidone to aripiprazole in youngsters aged 8-18 years, with psychotic symptoms who have responded unsatisfactorily to at least one other adequate trial of an antipsychotic. To read more about this study and to see if your child qualifies, go to www.ClinicalTrials.gov and type in aripiprazole.

We are forever walking a fine line between that all-important emotion called hope, and a need to stay open-minded and await the data. One of the mothers we quoted above, put it so wisely when she wrote:

Although this medication has been wonderful for my son, I would not want to raise hopes for other bipolar parents by singing its praises too much. I know how it felt when I heard wonderful things, hopeful things, about other medications that were found to be effective with bipolar disorder. As the parent of a bipolar child, when getting overly hopeful about a medication and then going through the painful and frustrating experience of trying it only to find it did not work (or worse--it exacerbated the symptoms of the bipolar disorder), it was heartbreaking. I guess with all the variations in brain chemistries unique to individuals with bipolar disorder (or any other psychiatric illness), there can't be one medication, the medication, that cures bipolar disorder. I think all parents need to be reminded of this so they're not setting themselves up for a fall

We've said it before, and it bears repeating again: If your child is doing well on his or her present medications, it is unwise to change the regimen because you read about a new drug--here or anywhere. If your child is stable, do nothing to rock that blessed boat.

We will continue to gather information about Abilify and its effect on children suffering with bipolar disorder, both on the research and the clinical fronts, and we would appreciate hearing from any of you whose children have had experience with it.

At this time of mid-winter and always, we wish you and your children the best,
Janice Papolos and Demitri F. Papolos, M.D.

Bibliography

Baldessarini, R.J. E-mail correspondence of February 5, 6, and 10, 2003.

Behr, Raymond. E-mail correspondence of February 4, 2003. Telephone Conversation Of February 10, 2003.

Burris, KD, Molski TF, et al. Aripiprazole, A novel antipsychotic is a high-affinity partial agonist at human dopamine D2 receptors. Journal of Pharmacological Exp Ther 2002;302-389.

Goodnick, PJ, and Jerry, JM. Aripiprazole: Profile on efficacy and safety. Expert Opinion Pharmacotherapy 2002; 12: 1773-1781.

Jody, Darlene, Ronald Marcus, Paul Keck, et al. "Aripiprazole vs. placebo in acute mania. (poster), Proc Am Psychiatr Assoc Annual Meeting, May 2002.

McGavin JK, Goa KL. Aripiprazole. CNS Drugs 2002; 16: 779-786.

Papolos, DF. and Papolos J. The Bipolar Child, Revised Edition. New York: Broadway Books, 2002.

Papolos, J and DF. Papolos. The Bipolar Child Newsletters Volumes 5 and 10. (www.bipolarchild.com)

Pavuluri, MN. E-mail correspondence of Feburary 3 and 4, 2003.

The authors would like to thank Mani N. Pavuluri, M.D., Raymond Behr, M.D., David Cremer, M.D., Robert McQuade, Ph.D., Mort Fineberg, Mary Fineberg, Catherine Schwartz, Niki Tenn, and especially, Deborah Storms, for their contributions to this newsletter. For his abiding interest, wisdom, and friendship, as well as his specific help with this report, we acknowledge Ross J. Baldessarini, M.D.

This newsletter is a tad late because we’ve been so busy with the publication of the revised and expanded edition of The Bipolar Child, and because we’re continuing to develop the research programs of the Juvenile Bipolar Research Foundation.

A few weeks ago JBRF launched its new educational forum for parents and educators, and if you haven’t had a chance to visit yet, there is an extremely comprehensive monograph entitled “The Educational Issues of Students with Bipolar Disorder” that has been sighted at IEP meetings in several states already. There is also an interactive bulletin board where a team of expert educators and advocates will answer questions pertaining to any part of the education process. It is the JBRF’s intention to establish and encourage an ongoing national dialogue that will promote a better understanding of the educational challenges that confront children and adolescents with bipolar disorder.

So if you have a question about your child’s IEP, or special ed law, or a Functional Behavior Assessment, or even home schooling, you’ll get timely answers that will do much to make your child’s experience at school more comfortable and beneficial. We welcome your visit at www.bpchildresearch.org (click on “Discussion Forums”).

In this month’s newsletter, we would like to explore a characteristic of many children with bipolar disorder that, while not initially as disruptive as rages and hypersexuality, nevertheless typically concludes in explosions and extremely battered feelings.

Mission Mode

Parents write to us often and mention that they are assailed all day long by their children’s intense need to buy something or to do something. The children seem to wake up, decide they have to go to the pet store and purchase a hamster or a puppy, or they just have to have the expensive sneakers that their friend is wearing, and no amount of reasoning or discussion can deter them from what parents describe as “Mission Mode.” Their sheer persistence is all-encompassing and they become very adept at blocking out any agenda but their own (which they are feeling very intently and very urgently). Parents, pummeled by this relentless pursuit of the child’s own need or his or her agenda, describe it thus:

He launched into what I call his “Mission Mode,” an insatiable state during which every thought that pops into his head becomes an obsession that must be relentlessly pursued. It doesn’t matter if it’s a must-have or a must-do. It could be the urgent need to go out and buy the new cereal he just saw on TV, or the sudden inspiration to mow the lawn when the neighbors are still sleeping. It’s as if his orders came down from God on a bolt of lightning.

Another mother from Oregon described her 11-year-old daughter this way:

Lauren tends to get stuck in this mode over things like wanting to go to the mall and go shopping. Right then, right there. Period. Doesn’t matter that it’s 9:00 at night, or some other impossible, inappropriate time. Trying to reason with her about why going to the mall right then is a bad idea--it NEVER helps. Reasoning with a child in this state is a disaster. She often then feels picked on and “unloved” (her words) because I don’t give in to her demands.

Sometimes “Mission Mode” can be a sign of impending mania, but not always; Sometimes there is more of an obsessional, anxiety component to it. The mother whose daughter needed to go to the mall despite its being closed also told us about her daughter’s urgent need to have her mother sit with her before dinner every night and do her homework, and that the child could not get past this worrying need. Her mother wrote:

It is frustrating when you want to eat dinner first, then do homework, but she is so anxious about getting it done and getting good grades that she won’t eat dinner until the homework is done. And she is not able to do it without me sitting right next to her. You can imagine how that plays out in the whole family. Lauren insists that I sit down then and there; Sam (my other child with bipolar disorder) is in his after-school hyper mode, running around the house needing attention to keep him calm, so he doesn’t trigger my husband who is also bipolar--and Cally (my five-year-old, non-bipolar child) is left to go color on her bedspread...and everyone is hungry and needing dinner.

Why are these children so absolutely rooted in their agendas? What is really going on here? And how can a parent deal with these urgent, obsessional needs and help the child become “unstuck” from these thoughts and demands?

Executive Function Deficits and the Bipolar Child

Some of the answers may lie in the fact that many of the children have deficits in the frontal lobe regions that govern the processes known as executive functions. The frontal lobes coordinate speech, reasoning, problem solving, strategizing, working memory, attention, self-control, motor sequencing, and other processes central to higher functioning. All human beings who approach a problem or a project must recruit executive functions that include analyzing a problem, anticipating problems, remaining flexible and reformulating a plan of attack if the assessment shows that the plan is not working (flexibility of thought and the ability to “shift set”). They also must keep a thought in mind while mustering the selected bits of information stored in memory so that this information can be brought to bear on the task (“working memory”).

It is now becoming apparent that children with bipolar disorder have deficits in just these areas. They are inflexible--they perseverate or can’t move off a topic, they can’t anticipate that this kind of behavior will bring negative reactions from those under assault by their perseverative plans, and they have impulse control problems and cannot wait for something. (They may also be anxious that they will forget what it is they want; or they may be using this sudden gusto about a project or new idea to focus their thinking.) The new idea may be a stabilizing force that supplies an external structure because deep down inside they are afraid they are disappearing down the rabbit hole. They experience their need as an emergency situation, and so urgent that it is as if their very survival depends on their getting whatever it is they think they have to have. Any refusal on the parent’s part seems to make them feel unprotected and unloved.

Dr. Nancy Austin, a psychologist in New York City who works with many children who have been diagnosed with bipolar disorder has written that:

The fundamental motivation of bipolar children’s behavior may very well be to find a way to regulate a biologically compromised, dysregulated system. Behaviors can be adaptive, such as “I need a break before I continue with my schoolwork,” or nonadaptive, such as this relentless pursuit of needs.

She goes on to say:

As we know, children who have bipolar disorder have intense responses to any perceived or biological stress. Stress causes shifting mood states. Shifting moods means shifting cognitive capacities, and especially vulnerable is memory. Intense moods result in cognitive rigidity and irrational thoughts. A quick fix may very well be the only option a stressed child grappling with bipolar disorder can think of to “soothe the wild beast inside.” If the child has no cognitive flexibility and may have some irrational assumptions, no amount of parental reasoning will be successful.

We asked Dr. Austin what she would advise a parent to do when confronted on a school day with the demand that a hamster be purchased as soon as the school bus deposits the child back to the home at 3:00 p.m. She said:

It’s true that children with bipolar disorder can be hyperfocused, but the parent must also be hyperfocused, and must stay focused on the task at hand. So, for example, if the child is getting ready for school and the “relentless demand” is getting a pet hamster, the parent might go through the following:

1. Don’t respond immediately, think: “Stay calm.” Respond neutrally and slowly.
2. Decide if this is a demand that you are willing to accept. If yes, then do so evenhandedly and without resentment. If not, move on to step #3.
3. Refocus on the task at hand. Speak in short, direct phrases, repeating the same phrase. Make no promises. For example, if the next task is for the child to put on his or her pants, say something like: “Right now, it’s time to put on your pants.” (The child may whine and cry and say that you’re a terrible parent --or much worse). You ignore these reactions. You repeat what you said before, more slowly, more quietly, without looking the child in the eyes (any added stimulation might add to escalation rather than de-escalation). You do this repeatedly until the child knows that he or she will get no other response from you except, “Pants on time.”

Dr. Austin cautions the parent to ignore any verbal responses from the child that don’t pertain to a positive indication that he or she is putting on pants. “This way,” she says, “you are not inadvertently negatively reinforcing a noxious behavior. You are trying to extinguish it.”

If the child hits, or throws objects, it suggests signs of medical instability and the parent should speak to the psychiatrist. But it may be that a pattern has been established and that the child is incapable of disengaging from the obsessive thought.

Dr. Austin then added:

Parents need to continue to be disengaged from the demand that’s in the child’s head. Remember, it’s a ‘quick fix” to activate a distressed biological system and maladaptive. Parents need to come down on the other side--they need to model by speaking quietly, neutrally, and slowly, asking for the child to accomplish a simple task that he or she is capable of doing.

Dr. Austin wants to remind parents that the child must shift mood in order for a more rational solution to be available to him. Also, that the child may have specific fears (rational or irrational) about school and that this “quick fix” means that these concerns may have not been totally addressed (an enormous job in and of itself).

It’s Not About the Sneakers

We next spoke with Dr. Paul Schottland, a cognitive psychologist in Florham Park, New Jersey, about the bipolar child’s often relentless pursuit of his or her own needs, and he also spoke about the children’s lack of flexibility. He too described how they get caught up in something and can’t let go (they can’t “shift set”). He said: “They don’t realize their thinking is rigid. They have to be taught to activate the flexibility of their thinking.”

These children often lack anticipatory thinking: They don’t process that if they get louder and louder they will not get what they want, and will perhaps be punished. They also can look as if they lack empathy or connection to the parent when they’re actually having difficulty picking up cues that would help them moderate their responses. They can’t think: “What would it be like for Mom to have to drive to the mall at this hour of the evening?” They cannot move ahead and think into a future situation, and they lack the concept of compromise. (Again we go back to the executive function deficits these children seem to have.)

“It is not about the hamster, or the sneakers,” says Dr. Schottland. “It’s about the inability to cope with his not getting what he thinks he needs at that moment. His system is not sophisticated enough to cope, it’s not that he is a bad child. This unreasonableness is a handicap and it is the handicap that must be addressed.

He continued:

A parent must ask him-or-herself: “What does my child need that she doesn’t have? How can I build in a structure that doesn’t exist?” The parents have to see themselves as more than providers and disciplinarians. The parents must think:” Part of our job is to teach her to develop the necessary structures that will help her cope.” This takes you out of the adversarial role and puts you in the role of teacher and parent.

Installing the Software

We liked Dr. Schottland’s computer analogy when he instructs the parent to “install the software that isn’t there on the hard drive.” It doesn’t come up on their screens naturally the way it does with other children, and it must be manually installed by the parents. And then it must be trained in by the parents.

Dr. Schottland talked through an example. Let’s go back to the sneakers. They cost $125.00 and there is no way the parent can grant the request. Things escalate and the parent becomes more exasperated and then the child blows. A rage ensues that shakes both the parent and the child. Let’s pick it up from there. Dr. Schottland says:

Wait until the emotions settle. Then approach the child and talk about the situation. Say something like: “This is not a good situation. We have to figure out a better way to make it better next time because I love you and I don’t want us to be this way.”

So you establish the fact that it is a problem that he or she has had for a long time and then explain that you understand how difficult it is for him or her and how upsetting it is. Then the parent can say: “Let’s find some tools so you can think things through differently next time so that the situation doesn’t have to repeat itself. I don’t like when we’re angry at each other.” (This is a bonding response, not an adversarial response.)

The parent then continues: “I love you and I would do that for you if I could.” And then the parent can ask: “What can you say in your own mind that could help you deal with something I can’t do at that time? “

Cognitive Mediators

Dr. Schottland gives the child something called a “cognitive mediator.” It is a thought that can replace the uncomfortable thought they are thinking. This new thought can get them unstuck from the rigid place in their thinking, and it can mediate the experience of the situation and therefore affect the response and outcome. He actually writes the cognitive mediator out on a card for the child.

“It’s like installing the executive functions that are not there or are not working correctly,” says Dr. Schottland. “You have to give them these tools. So, when the child is calm and you’re quietly discussing what happened, the parent can say: ‘It’s not your fault you get stuck, you push too hard, but we have to learn how to replace that thought with another.’”

Here’s an example of a cognitive mediator:

In reality you’re lucky if you get what you want fifty percent of the time. You should ask for something, and then ask one more time, but if I say “no”--can you picture yourself putting it on the shelf? Imagine saying to yourself: “She said no. I’ll put it on the shelf and come back to it later.” (This shifts the obsessive thought away from the child and he or she spends time imagining it on the shelf and chances are that that cognitive shift will help get the child “unstuck.”)

Another cognitive mediator: “I won’t get it this time but maybe I’ll have a good shot at the next thing I ask for.“ (You’re helping them adapt to reality).

A parent and a child can generate cognitive mediators together. Parents need to understand that that the child has little ability to grasp the whole picture in the moment. Instead, he or she gets carried away with the emotion and loses the capacity to hold the complete picture and understand and anticipate that there may just be alternatives that can work in an interactive situation. Any possibility of that gets shut down as they perseverate and escalate about the one thing they think they have to have at that moment.

Parents must remediate this weakness by not giving in and teaching them to activate their executive functions and flex their cognitive thinking.
They need to coach the child and act pre-emptively when another hamster or sneaker mission begins to develop. If they see “Mission Mode” they must alert the child to start using clues. Use a conversational tone.

Parent: “I think this could develop into something that neither of us would like. It’s starting to feel to me like last time over the sneakers. Do you feel that? Do you see that?

Child: “Yes, but I really want (escalation)...”

Parent:“I would love to do that if I could but this is one of those times that I can’t. Let’s think about something else.”

Again, the parent needs to start them reflecting on the whole picture. They can’t access the emotion or the memory of the past negative sneaker experience and decide to let this one go because they have such difficulty retrieving emotional response from the past or thinking forward into the future . This kind of moving back and forth requires a cognitive flexibility--the very thing they lack.

“This is such a job for a kid,” says Dr. Schottland. “Show him how you appreciate how hard he’s working and every once in a while reward him.”

Dr. Schottland also warned that this is a process that takes a tremendous amount of effort on the parents’ part. It is not a quick fix, but must be trained into the child over and over again. He tells the parents, only half-jokingly: “Get back to me after a thousand trials.”

He closed our conversation by adding:

You have to understand that you could do this all one hundred percent right, one hundred percent of the time, and you still might not get what you want. Don’t judge yourself by how the child responds, but by how you respond. Are you responding neutrally, empathically, are you giving the child the tools? Are you enhancing the soul of the child?

Remember that you are always installing the software of how the child feels. If you install an empathic, caring, problem-solving part inside them, you’ve done your job.

And under circumstances that would try the patience of a saint.

Dr. Austin also followed up our conversation with an email in which she said:

This is, of course, an enormous amount to ask of parents. But evaluating how much time parents get pulled into conflict over an irrational or unacceptable demand, perhaps a focused response, over time, will help extinguish more of this kind of annoying behavior. If parents are successful at this, they are empowered, no matter how many times they have to go through the routine. If parents are consistent, the child will realize the “demandingness” is useless and begin to try alternative, more adaptive responses (because they now realize there are alternatives). This allows the child’s cognition to flex, at least a little. Developmentally, adaptive responses can stem from the creative capabilities of the child. And, as we all know, children with bipolar disorder often have a great creative ability that it unavailable to them during a “mood storm.”

And what about Lauren who can’t do her homework without her mother at her side? According to Dr. Schottland, she needs to work with the catastrophic thought that generates such anxiety. She needs a tool with which to work on her own anxiety and replace it with a thought that helps her to be more flexible. A therapist could help her digest the toxic thought--metabolize it and prove to herself that she can do it, after dinner, or without her Mom.

In fact, her mother emailed and told us:

I will talk to Lauren when she needs to talk to me. Usually, taking ten minutes to talk to her at an inconvenient time helps to prevent a night of perseverating and driving us all crazy. So I guess my advice on coping with this behavior when it is emotional/anxiety-related is to deal with the pressing issue. She will not get past this stuck thinking on her own.

Lauren’s mother also noted that with time and maturity, things improved. “Lauren has learned some of her own skills,” she wrote. “She has learned to use email and instant-messaging to communicate with other friends and family members who can support her when I might not be able to.”

We remember when we were expecting our first child, there was a seemingly vital debate on whether a MacClaren or an Aprica stroller was the best you could buy for your new baby. Purchasing one or the other seemed to say something about what kind of parent you might turn out to be. Would anyone have guessed that parenthood would hold unstable, suffering children, multiple medication trials, school problems and IEPs, hospitalizations, and this kind of working through of every thought and impulse?

For the parents of children with bipolar disorder, it does; and we are in awe of your sheer stamina and determination to make things right. We hope this helps you feel better, cope better, and feel more satisfaction in your role as a parent. We also hope it helps remediate some of the cognitive weaknesses that are no fault of the child’s, but that make life for him or her and for the entire family so fraught with negative feeling and emotion.

As always, we send you our best and look forward to hearing from you,
Janice Papolos and Demitri Papolos, M.D.

Bibliography:

Papolos, Demitri, and Janice Papolos. The Bipolar Child, Revised and Expanded Edition. New York: Broadway Books, 2002. (To read more about executive functions and the neuropsychological testing that reveals
weaknesses in the frontal lobes, read Chapter 11.)

The authors wish to express their gratitude to Cheryll Hart, Jeanne Langer, Cheryl Matalene, and Drs. Nancy Austin and Paul Schottland.

The past few months have been busy as we readied the revision of The Bipolar Child for its September publication date, and as we continue to launch the first programs of the Juvenile Bipolar Research Foundation. Last week JBRF launched its professional listserv for physicians. This is the first online forum for physicians from around the world who treat or supervise the treatment of children and adolescents diagnosed with bipolar disorder. The board of JBRF is extremely concerned that there are only 6300 child psychiatrists throughout this country (most residing in more urban areas) and we hear from parents everyday who cannot find a doctor to evaluate, diagnose and treat their children. JBRF envisions that this listserv, a rapid peer consultation service for those on the front lines, will provide an efficient vehicle for members to learn and communicate about clinical experience, differential diagnosis, treatment outcomes, and adverse effects to medications. It is also the JBRF’s hope that pediatricians and family practitioners will join this forum as they are the ones who first see these children and, in many rural areas, they will have to oversee their treatment as there are no child psychiatrists to whom they can refer.

In the next few weeks, JBRF will begin subscribing psychologists, neuropsychologists, social workers and therapists to a second professional listserv so that professionals seeing these children can share information and ideas as to what works best for the children and their families. Discussions about neuropsychological testing and remediation techniques will also take place in this forum.

If you know child or adult psychiatrists, pediatric neurologists, family practitioners and pediatricians and other mental health professionals who would like to join an important and informative online discussion group, please have them contact Sandra Norelli at sandi@jbrf.org and visit www.bpchildresearch.org. Please feel free to forward this newsletter to doctors and therapists and pediatricians who work with your children.

Past issues of this newsletter have focused on aggression, night terrors, separation anxiety, sensory integration problems, and other symptoms of early-onset bipolar disorder, but we feel it’s time to discuss a very common symptom of the illness -- one that particularly affects and disturbs the families of the children, one that is rarely talked about, and one that leaves us all uncomfortable: hypersexuality.

Hypersexuality in children is rarely discussed about for two reasons: one is that (bipolar or not) sexuality in children is simply not spoken about in public; and the other, sadly, is that parents of hypersexual children are afraid to mention the subject -- even over email. They are petrified that Child Protective Services will find out and wrongly assume that a hypersexual child is an overstimulated child, and that that overstimulation stems from sexual abuse in the home. Few people -- even the professionals at the Departments of Child and Families (DCF) or Child Protective Services (CPS) realize that hypersexuality is so common during the manic or hypomanic stages of bipolar disorder (in adults and in children) -- and so it is rarely if ever factored into the equation. Parents of bipolar children fear losing custody of their children based on these suspicions of abuse.

In the pages below, we’ll discuss the subject forthrightly -- what it is, why it is, and how to deal with sensuous demands or behaviors in ways that are not punitive and shameful for the child. Hopefully, some of the things you’ll read here will also help a child gain more control.

What Is the Definition of Hypersexuality?

Webster’s New Collegiate Dictionary describes “hypersexual” as “unusually or excessively interested in or concerned with sexual activity.” It is an accepted fact that hypersexuality is a symptom of hypomania or mania in an adult who has bipolar disorder. In Overcoming Depression, 3rd Edition, we wrote about the increased sociability that accompanies an upswing in mood and stated that “often accompanying this increased sociability is an increased sexual drive (hypersexuality). It is not uncommon for the person to ‘fall in love’ and impetuously pursue a love affair or a string of affairs, possibly jeopardizing an established relationship or marriage.” In another section, a man describes some of the sensations he felt early in a manic phase: “Sexually I felt awakened, competent, responsive...” Hypersexuality is a very common symptom of mania.

In children, the symptom may manifest as a fascination with private parts and an increase in self-stimulatory behaviors, a precocious interest in things of a sexual nature, and language laced with highly sexual words or phrases.

If aggression is difficult to explain to the neighbors, what do you do with little ones who always have their hands down their pants, whose language may be filled with sexual jargon, or who are constantly trying to rub their bodies up against an adult?

In the same way that children with bipolar disorder have difficulty modulating aggressive impulses, so do they sometimes have problems reigning in sexual impulses that may overtake them and cause them to overreach the boundaries of what is appropriate in a social context --particularly in hypomanic or manic states where all systems rev up. They seem on a different time clock than other children, as though certain behaviors set to go off in the adolescent years happen well before. Yet doctors, nurses and social workers in this country are taught routinely that any sign of increased sexual behavior in children is a result of overstimulation in the home environment.

But is this so? When Dr. Barbara Geller and her colleagues at Washington University in St. Louis looked at a group of 93 children and adolescents diagnosed with bipolar disorder as a part of an ongoing NIMH-supported phenomenology study, they found that 43% of this group who were manic were also hypersexual. In order to rule out any overstimulation or sexual abuse in the environment, each child and family was examined first with the Psychosocial Schedule for School-age Children Revised (PSS-R).

Dr. Geller explained:

This is a comprehensive semi-structured interview that was given by the research nurses separately to mothers about their children and to children about themselves. It has a section with items on sexual abuse. In addition, pediatric and other medical records were obtained and examined for any possible clues to abuse (e.g., multiple visits for accidents, unusual urinary problems etc.). Teachers and after school caretakers also supplied information.

Dr. Geller and her colleagues found that less than 1% of these hypersexual bipolar children had evidence of overstimulation or sexual abuse in the home environment. The conclusion of one of the journal articles published about this on-going study of children and adolescents with bipolar disorder was that “the 43.0% rate of hypersexuality in the prepubertal and early adolescent subjects strongly supports hypersexuality as a symptom of mania.”

What Does Hypersexuality in a Child Look Like? How Early Does It Begin?

Danielle Steele, in her book His Bright Light, describes her son Nick’s intense interest in women at the age of two (italics ours).

She wrote that:

He was absolutely enamored of women. And just as I had thought early on, he often seemed to me like a grown man in a toddler’s body. ....He groped, he hugged, he caressed, and who would expect a two-year-old of anything other than being cuddly? I did. I knew him better. Even at two, Nick was a Don Juan in the making.

She continued:

He used to sneak up behind my housekeeper, creep under her skirt and pat her bottom, and then laugh outrageously. When I took him to our neighborhood ice cream store for an ice cream cone, he would invariably stand in line with a look of innocence, and reach up to a comfortable height for him and pat some woman’s bottom.....And when we went to a beach house we still rented then, he would cheerfully suggest we go down to the beach and “hug the ladies.”

While most children possess some curiosity and interest in their body orifices, many of the parents we interviewed for this article described their children as intently keyed into body parts and talking about them all the time, especially during periods of instability. A little girl talked endlessly about her “butt,” and a three-year-old boy asked his mother to “rub his penis”. When in a silly, giddy mood one boy screams “Tickle me penis” over and over and breaks up laughing about it. Another little boy told his mother “It feels really good to stick my finger up my butt.”

Almost every mother described some variation of the child’s hugging or kissing her in an extremely sensual way. A mother emailed us that: “He loves to smash his face into my breasts when he hugs me and he constantly begs to ‘squish my big, fat tummy’ (this woman is very slim and trim). He usually has his hands on me before I can pry him off.”

We heard many stories of both boys and girls watching TV with their hands down their pants or little boys holding onto their penises for hours of the day or evening. One mother wrote about her 6-year-old son:

Hypersexuality is the most disturbing symptom for Matthew after the aggression and rages are gone, and it’s one of the last behaviors to go away as treatment is effective for him. For instance, today, despite a lithium increase, he’s had his hand on his penis all night. I told him over and over again to put his hands somewhere else, but to no avail. Now, granted this is minor compared to two nights ago when he threatened to hit our privates so hard it hurt (as revenge for a simple “no”). If this lithium increase works as others have, tomorrow night or the next, Matthew should not exhibit hypersexuality unless he needs a higher lithium level for the umpteenth time. Sometimes, we see minor signs of the hypersexuality right before the needed lithium dose.

Here is another description of a very hypomanic, hypersexual seven-year-old boy:

He got very silly after dinner -- very affectionate with me, and hypersexual at bath time. He said: “I love you Mommy,” trying to kiss me. “Will you lay on top of me. I’m going to rub my penis, can you do it?” After his bath he jumped on top of me trying to give me “long kisses” and telling my husband he knows a girl who would rub his penis.

How Can a Parent Effectively Deal with Hypersexuality?

Almost all the parents we interviewed said the hypersexual symptoms disappeared with proper stabilization, but until that day arrives, a parent whose child is hypersexual is going to have to contend with the conversations and behaviors and, embarrassed or not, model appropriate social behavior for the child -- without making the child feel shame.

We were very impressed by the handling of such delicate, uncomfortable material by the very wise women we spoke to and we would like to pass on their statements. Because it’s extremely difficult to think through appropriate responses to language and actions that happen almost out of the blue and that leave a parent gasping with shock and embarrassment, we thought these “fall-back lines” could help other parents address these behaviors and utterances simply and cogently.

Scenario: The child is running naked around the house. One mother described it and dealt with it this way:

He loves his body, loves how it feels and doesn’t have any impulse control. At 8 1/2 he’ll still run around the house naked, dancing to a rock song. I calmly say: ‘Come on sweetie, put some clothes on.’ I don’t over discuss it or give it too much attention, but he is definitely ‘Naked King of the Moment.’ It goes along with everything about them -- they’re just out there and I understand that.

In response to his nakedness she said: “Your penis and testicles and butt are very special and will be throughout your life. But you notice that even in the pool, this is the one area people cover up and still keep private. Why? Because it’s so special.”

Scenario: The child is trying to kiss a parent on the mouth in a sensuous manner. His mother replied: “Honey, this is a special kiss; something a Mommy and a Daddy do, and you will do it as an adult when you feel very close to someone. But it’s not a Mommy-son kiss. We have a special kiss.” (She demonstrates kissing him on both cheeks and then giving him a big hug.)

This same mother also had to respond to her three-year-old sticking his finger up his anus all the time and when she told him not to do that in public he responded: “But it feels so good.” She said:

That’s great. It should feel good, but look around you, do you see anyone else in this house doing that? Do you see anyone at school doing that?” So, you have to figure out what is private and what is not. (This mother wanted her little boy to start looking around and seeing what’s normal or acceptable.)

She then had a very frank discussion with him:

Honey, what comes out of your body is meant to come out (mucus, urine, feces) it’s your body’s natural way of letting go of what is no longer needed and shouldn’t be there, and you could get germs if you do that. It makes sense to do that in the bathtub if you want to because you’re using soap and you can clean your hands immediately and they will get clean and smell clean. But, anywhere else and you will smell like poop and you don’t want the kids to think you smell like poop. (This made sense to him.)

Scenario: Your child asks you to lay down with him or her at night because she or he is afraid (whether it be separation anxiety or fear of night terrors). One mother explained her system to avoid their bodies touching and any overarousal taking place:

I never get under the blanket with him . It would be too stimulating. I wrap him in a cotton blanket and turn the air conditioner on or open the window (he is always hot) and once he’s papoosed like this, I may lie down on the bed across from him or sit there awhile. The blanket gives him a physical, hugged feeling, and separates our bodies.

She concluded our interview by stating: “Now that he’s treated, it’s not such a problem anymore.”

Hypersexuality in the Dreaded Teenage Years

Since over 50% of American teenagers are having sex, adolescence becomes even more loaded for parents of a teenager who may be unstable at times and exhibit periods of hypersexuality. As we wrote in The Bipolar Child:

So many parents have described watching with horror as their daughters get “dressed” in the skimpiest of outfits and attempt to go out flaunting their bodies to cadres of boys in the neighborhood and school. One girl we knew was so hypersexual that she and her boyfriend were practicing heavy petting in the school library for all to see. We have heard of many boys making calls to 1-900 numbers.

The first thing parents of such a teenager should do is call the treating psychiatrist and get the teen’s blood levels checked. The hypersexuality may be a sign that the levels have dropped or the teen is being noncompliant. (In an adolescent with no history of the disorder, the hypersexuality may be a symptom of the impending illness, not an indication that the teen is amoral.) We then go on to suggest that perhaps the teen should be kept home from school for a few days while the meds are adjusted and to keep him or her out of trouble. Again, stability seems to be the key to all things good.

How Does a Parent Feel About This Hpersexuality?

No parent rejoices in dealing with a child’s sexual life, and no parent ever imagines that he or she will be confronted with this aspect of a child’s behavior or interest so early in the game. It catches parents unprepared. Parents can become overwrought about how it will affect siblings -- older or younger -- and the outside world who will somehow think they are “doing something.” How strictly the subject of sexuality was dealt with in their families of origin will account for many of the feelings that may flood parents when they witness (or are the object of) such behavior. All parents have heard stories of children being taken out of the homes by CPS and so not only do they feel embarrassment and confusion, but profound threat. They also fear that neighbors or other family members will see this going on and not allow their kids to play with their own child.

There are other feelings. One mother, whose eight-year-old son became very manic this spring, leaned over to get something from the refrigerator and felt him stick a hairbrush up her skirt. This kind of impulsive, unexplainable action, and his early interest in women’s breasts and body parts leave her in a tumult of guilt and confusion. She’s constantly asking herself: Did I do something wrong? Where does he get this from?

She told us: “I find the hypersexuality directed at me disgusting. I’m not a prudish person, but I find it so awkward and scary. It goes against all of society’s norms and dictates.”

Most of the parents were especially surprised by their children’s precocious knowledge as they know how sensitive these children are and prone to night terrors and bad dreams and so they screen all television, movies, and popular media that might expose the children to anything scary, overstimulating, or sexual. Eric’s mother wrote of her own confusion about her son’s knowledge:

I am shocked that embarrassing hypersexual behavior shows up in bp kids despite the fact that most of our kids have NOT been exposed to sexually explicit media images But my point is, not only are our kids not sexually abused, they also tend to have LESS exposure to any sexual images than other kids, because we parents of bp kids are hypervigilant about what they see, and we screen everything. Eric, for example, does not watch any network or cable TV, does not see any sexually explicit materials, does not know any descriptive sexual words, other than basic boys' and girls' anatomy, and he has a couple of rather conservative (my sister would say "nerdy") parents. Yet, he displays blatant hypersexuality when unstable. WHERE does it come from?

It may be that these children are so exquisitely attuned to things that they hear -- snatches of lyrics in a parking lot as they walk to a store with a parent, or see a television commercial at a friend’s or relative’s house, or they overhear something at school and it simply makes a bigger impression on them. We can’t say for sure.

What Should A Parent Do to Protect the Child and the Family?

Many parents expressed their concerns that the child’s “out-there” flaunting of his or her body and suggestive talk could open the door to a sick outsider taking advantage of the situation, and they realize that they need to educate the child from a young age about any possible consequences of such talk and behavior. One mother, whose very young son became hypersexual during a period of instability and asked her: “Could you rub my penis?” told him: “If anyone ever tries to touch your body in any way, you tell Mommy and Daddy right away. No matter what you say, no one should ever be touching you anywhere near your private parts. She is worried sick about his being so inviting and open about himself sexually. (As though there isn’t enough to worry about with a child with bipolar disorder...)

Siblings may be pulled into games of “Doctor” and a few parents reported that, understanding there might be periods of hypersexuality, they watch their children like hawks. Most understood that the children should not bathe, shower or sleep together (or with a parent) and that separation was something to be imposed if signs of hypomania and hypersexuality were seen. One mother said: We’re buying a new house and I want each of the kids to have his own room. Next year I’m sending the two boys to opposite days of preschool so that they aren’t together as much.”

One woman was in the middle of typing an email to us when she wrote:

As a matter of fact, I just had to stop typing in order to separate him from his eight-year-old sister. He was sucking her toes and told me that he was “shaking my booty “ (he was provocatively swinging around while gyrating at the hips and sticking his derriere out). I have no clue where he heard that one. Whenever the hypomania starts, so starts the sexually-related jargon and actions. It is one of our "Oh no, here he goes" signs. I try not to think too long about what the teenage years could hold if this continues. We are hopeful that through time he will be in better control and be aware of the dangers of such sexually-oriented behaviors and recognize them as warning signs.

She told us what she says to him about his behavior and language:

We have had one-on-one conversations stating that our actions can make others uncomfortable and that some actions are OK in one place but not another. I referred to church. It is not OK to be loud and run around in that situation, however, at home playing that way is all right. So, when he is doing something like sucking his sister's toes I gently guide his shoulders the other way, look him in the eyes and say: "Uncomfortable." Then I get him into a different activity.

When we asked her how her daughter deals with all this. She said:

As far as our daughter is concerned, she recoils and says, "Stop it! I don't like that". By this time, I'm usually on the scene. I've also explained to her that her brother has trouble thinking before acting and that is usually when his mood is hyped up. She kind of lumps this into the same category as his outbursts. She understands that such behavior is not acceptable and we are to know when it happens. Each of the kids has his or her own "private" place in our living room. Only Mom and Dad can interrupt that space. This is to give her some place to go.

Several mothers were having this discussion on a listserv we’re on, and one woman advised the group to have the treating psychiatrist document the hypersexual behaviors or language in the child’s medical records and to keep a copy of these in a binder at home. This way if that knock on the door from CPS ever comes, a medical document exists, detailing exactly what’s been happening -- that the child when manic tends to exhibit sexual behaviors or language. Medical documentation can help explain the situation before suspicions outpace knowledge.

The mothers also warned each other against telling anyone who doesn’t need to know. It's just something that neighbors, teachers, or even relatives cannot easily understand, and may in fact misinterpret.

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Some days, in dark moments, we wonder if the Powers Above decided to experiment to see just how much these earth beings called parents could withstand. If the aggression and mood swings of the unstable child don’t get to them, than maybe the hypersexuality will. However, these children do gain control as they become stable and more mature, and -- as we see in the stories above -- there is much that parents can teach. No doubt the sensuality and sensitivity of these children will make them highly attentive partners when they become adults.

All we can say is that we salute these brave parents who have so much to contend with and do it with such grace and wisdom. We thank them for sharing their thoughts and phrasing about this sensitive subject, and to Dr. Barbara Geller for her pioneering research in this area and for contributing to this article.

We’ll write again soon, but, as always, we wish you and your children healthy and stable summer days and nights.

Janice Papolos and Demitri Papolos, M.D.

Bibliography:

Geller, Barbara, Kristine Bolhofner, et al. “Psychosocial Functioning in a Preputeral and Early Adolescent Bipolar Disorder Phenotype.” Journal of the American Academy of Child and Adolescent Psychiatry 39 (December 2000):1543-48.

Geller, Barbara, Betsey Zimmerman, et al. “Diagnostic Characteristics of 93 Cases of a Prepubertal and Early Adolescent Bipolar Disorder Phenotype by Gender, Puberty, and Comorbid Attention Deficit Hyperactivity Disorder.” Journal of Child and Adolescent Psychopharmacology 10 (2000): 157-164.

Geller, Barbara, Betsey Zimmerman, et al. "DSM-IV Mania Symptoms in a Prepubertal and Early Adolescent Bipolar Disorder Phenotype Compared to Attention-deficit Hyperactive and Normal Controls." Journal of Child and Adolescent Psychopharmacology 12 (2002): 11-25.

Geller Barbara, Marlene Williams, Betsey Zimmerman, Jeanne Frazier. Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia (WASH-U-KSADS). Washington University, St. Louis, MO, 1996

Papolos, Demitri, and Janice Papolos. Overcoming Depression, 3rd Edition. New York: HarperCollins, 1997.

Papolos, Demitri, and Janice Papolos. The Bipolar Child. New York: Broadway Books, 1999.

All of us know that being pudgy or husky can affect a child’s self-esteem, but it wasn’t until we saw a segment that John Stossel did several years ago for ABC’s 20/20, that we realized just how awful children feel about being overweight. John Stossel sat down with a class of kids in late elementary school (if we remember this correctly) and talked with them about being a “fat kid.” At some point in the conversation, he asked them if they had a choice of being fat or of having one arm, which would they choose? His shock mirrored ours when—to a child—they opted to have one arm. Despite his cogent argument that you could always lose weight but you could never regain the arm, he was unable to budge them on their decisions.

So, understanding this, imagine a child who has to deal with rapid mood swings, irritability, anxiety, rage, perhaps learning disabilities (we shall talk about new findings in this area in a future newsletter), and psychosis, and is now being turned into a rather “rubbery” kid by many of the medications used to treat all of the just-mentioned symptoms.

Doctors and parents should do everything to lessen this burden on the child. If a child is on the hefty side, a mood stabilizer that is known not to cause weight gain might be tried first. Depakote and lithium tend to cause weight-gain in youngsters (not all, however) and Trileptal (oxcarbazepine) and Tegretol (carbamazepine) seem to cause less weight gain. Topamax (topiramate) is an add-on mood stabilizer that actually causes weight loss, but at higher levels it can cause a cognitive dulling, and it is not often used as a monotherapy.

The atypical antipsychotics cause by far the most weight gain and Clozaril (clozapine) and Zyprexa (olanzapine) are the worst offenders. Risperdal (risperidone) causes less weight gain than Clozaril and Zyprexa, but still adds some very unwanted pounds; and Seroquel (quetiapine) seems to be intermediate in risk between Risperdal and other antipsychotic durgs. The new atypical, Geodon (ziprasidone) seems to be weight-neutral.

High hopes were pinned on Geodon because of it lack of weight-gain, but we have heard of quite a few cases of an over-arousal syndrome caused by Geodon, perhaps due to its SSRI-like activity. The jury is still out, but it has not proven to be a great boon for children with bipolar disorder as of this writing.

The atypical antipsychotic medications are increasingly prescribed for children with bipolar disorder because they target some symptoms that the mood stabilizers do not. The atypicals may be of particular benefit to children who have prolonged rage attacks, mixed-irritable moods, psychotic symptoms, and possibly very rapid cycling of mood. They also reduce anxiety and agitation, and since children with bipolar disorder cycle so rapidly and often become caught in mixed states where anxiety and agitation are dominant symptoms, the atypicals can be especially effective.

In fact, the atypicals (with their reduced risk of movement disorders) are even being used as a monotherapy for mood stabilization (this discussion can be reviewed in our Fall 2000 newsletter).

The Medical Implications

In our newsletter of Fall, 2000, we first sounded some concerns about a series of general medical, metabolic problems that were being increasingly reported in association with some of the new atypical antipsychotic medications. These include new-onset, type II (non-insulin dependent) diabetes mellitus, changes in lipid metabolism and blood concentrations, sometimes severe and persistent elevation of prolactin and other hormonal imbalances (milk oozes from children’s nipples) and a range of adverse cardiovascular effects that include low blood pressure and abnormal functioning of the heart. The long-term implications of such adverse effects are not known, particularly for youngsters that may need to remain on such medication for decades to come.

In recent months, more stories of emerging problems in the area of glucose metabolism and the development of type II diabetes have begun circulating in the clinical community.

Diabetes: Type I and Type II

Diabetes is a disease that affects the body’s ability to absorb and break down sugars. When a person is diabetic, either the body does not produce or does not properly utilize insulin (the hormone that allows glucose to enter the body’s cells and fuel them).

Type I diabetes mellitus is usually an autoimmune disease and is characterized by almost total loss of beta-cell insulin secretory function in the pancreas. The beta-cells are selectively destroyed. This type of diabetes is often referred to as juvenile-onset diabetes and requires daily insulin injections for life to be sustained.

Type II diabetes mellitus used to be called adult-onset diabetes, and is associated with a decreased sensitivity to the actions of insulin (insulin resistance), along with a variable and usually progressive defect in beta-cell function leading to a relative insulin deficiency.

The emergence of type II diabetes is highly correlated with weight-gain that often accompanies decreased physical activity. The risk for this kind of diabetes is increased by approximately two-fold in mildly obese people, and ten-fold in the more seriously obese. There is an increase of about 4.5% in risk for type II diabetes mellitus for every kilogram (2.2 pounds) increase in body weight.

Symptoms of type II diabetes are excessive thirst, excessive urination, extreme hunger, increased fatigue, irritability, blurry vision or unexplained weight loss (not usually seen when an atypical antipsychotic drug is in the picture). Since almost all of these symptoms can be side effects of psychiatric medications, a parent would be hard-pressed to know if a problem were developing. Often there are more subtle changes in the glucose levels and an emerging case of diabetes is not apparent for some time.

Why Do Atypicals Cause Weight Gain?

We once talked with a mother whose son gained two pounds a day on Zyprexa and continued at that pace until the doctor removed him from the medication. Why would some of the atypicals cause such remarkable weight gain? While it is not really understood completely, one theory postulates that the degree of weight gain is correlated with the drug’s affinity for histamine (H-1) receptors. Zyprexa and Clozaril have a greater affinity for H-1 receptors than do Risperdal and Seroquel. These drugs also seem to have synergistic effects on the H-1 receptors and certain serotonergic receptors, and thus cause more weight gain than other medications.

How Can Weight Gain Be Counteracted? Axid and Other Strategies

Medications with a high affinity for histamine H-1 receptors in the brain typically cause sedation and weight gain. Other medications that antagonize or block histamine H-2 receptors (those that control production of stomach acid) appear to attenuate weight-gain in some persons.

Pharmaceutical companies understand that medications that cause weight-gain are not medications that are going to be prescribed or taken, and they are looking for ways to counter any increasing poundage. Eli Lily, the pharmaceutical company that makes Zyprexa, also manufactures and has underwritten studies on a drug called Axid (nizatidine). It is a histamine H-2 blocking agent, as is Tagamet (cimetidine).

Breir and colleagues designed a well-thought-out double-blind, placebo-controlled trial of Axid for schizophrenic patients that involved132 patients taking 5 to 20 mg of Zyprexa a day. They were divided randomly into three groups: one received 150 mg of adjunctive Axid, twice a day; another group received 300 mg of Axid twice a day; and the third received a placebo with their Zyprexa. The study lasted for 16 weeks.

By week 16, the placebo-adjunct group had gained the most weight (an average of 5.51 kg, or 12.1 pounds). The patients assigned to 150 mg twice-a-day dosing gained an average of 4.41 kg (9.7 pounds); and the group assigned to the 300 twice-a-day dosing, gained the least amount of weight (2.76 kg, or 6.1 pounds). Moreover, with the higher dose of Axid, weight gain appeared to plateau by week eight.

So the patients given the higher dose of Axid still gained weight, but 77% less than if they hadn’t been given Axid at all, and 37% less than the group taking the lower daily dose of Axid.

Some psychiatrists experienced with the use of Axid have found that it must be used at the start of treatment with an atypical antipsychotic agent in order to be effective. One clinician we spoke with, child psychiatrist Lynne Brody of the Weil Cornell Medical Center in Westchester, New York, told us she has used Axid with a number of patients. She reported the following results: one eleven-year-old girl with bipolar disorder became hypomanic; one teenager returned to her normal weight on Axid as it seemed to reduce her appetite; and the remaining patients discontinued Axid because it seemed to make no difference.

No other physicians we interviewed have had great success using Axid to countering weight-gain, nor have we heard reports about the usefulness of another histamine H-2-blocker, Tagamet (cimetidine), which also blocks secretion of acid from the stomach and is said to reduce hunger.

Dr. Brody held out hope for a number of strategies that she institutes when she places a child on a potentially weight-increasing psychiatric drug. Not surprisingly, these involve diet and exercise.

Dr. Brody sits down with the parents alone and discusses her concerns about weight-gain and possible medical complications. If the child begins to gain weight, she encourages a program that will help counter the weight-gain. She wants the child to exercise as much as possible (at least five times a week, for 20–30 minutes at a time) and she sends the family to a nutritionist with a medical background who can individualize a nutritionally sound diet and who can teach the child to make better choices.

Dr. Brody realizes that children with bipolar disorder crave carbohydrates and sugary foods and that this is going to set up continuous fights with an already oppositional child. There will be times a parent may have to relax the rules and let the child indulge, but the life, health, and psychological well-being of the child is at stake, so it’s a fight that is going to have to be fought many times.

Dr. Brody then told us about two bipolar siblings that she sees in her practice. Their father set up a special system for them: they exercise for a reward. He bought an elliptical trainer and some weights. Once his teenage son began to build upper body strength and began to feel much better about his body image, he didn’t need so much rewarding. Dr. Brody reported that his new upper body strength brought about an unexpected bonus: his handwriting actually improved.

Finding an exercise program for a much younger child may be a bit more difficult, but tennis, swimming, and martial arts are activities to think about-- perhaps combined with bike riding, walking, or skating. A stationery bike in front of a television means less time driving in cars with drop offs and pick ups. (One should check with the child’s pediatrician before embarking on any exercise program.)

Exercise is a win-win situation because the child typically feels better physically and mentally after exercise. Moreover, exercise consumes calories and promotes leanness, and physical activity plays a major role in glucose metabolism: it lowers blood glucose and improves insulin sensitivity—all counteractions to the development of type II diabetes.

Other Options

If weight gain gets out of control, a doctor can try switching to another atypical such as Seroquel, or can add Topamax to the medication mix. Topamax can cause weight-loss, sometime an impressive amount. But Topamax often is excessively sedating and can cause cognitive blunting at higher levels. There is a (reportedly slight) risk of glaucoma at higher doses. However, if 50-75 mg of Topamax are taken at night, the drug promotes sleep and fights weight gain for quite a few children.

Medical Tests Needed When A Child or Adolescent Takes An Antipsychotic Medication

One of the original bonuses of the atypical antipsychotics--besides their lower risk of causing tardive dyskinesia-- was that they eliminated the need for blood levels and blood tests, a real boon for needle-phobic children and their parents. But as we’ve begun to see the emergence of irregularities in glucose metabolism that these medications can cause, recommendations of frequent testing have to be made.

It is recommended that prior to the institution of treatment with any atypical neuroleptic—particularly if long-term use is contemplated—a set of baseline medical measures be taken. These include measurements of weight, fasting blood glucose, glycosylated alpha-1c hemoglobin (an index of the efficiency of insulin action), and blood lipids. Children should be re-tested periodically (every 4–6 months) during treatment, and those who experience significant weight-gain or have a family history of diabetes should be monitored especially closely. Naturally, a child should be weighed every week and a chart kept so the doctor can assess the situation carefully.

Parents and physicians need to be vigilant about the potential complications of any medication a child is taking, and we’re sorry that the atypical antipschotics carry more of a potential shadow than originally thought. However, they are miracle drugs in many ways: they are life saving, they protect a child from the horrific fate of psychosis and unchecked rage or agitation, and in many cases, they allow a child a chance to grow up normally. And they often allow a family to be just that—a family.

In addition, the atypical antipsychotic drugs can significantly improve many aspects of cognitive functioning, including executive functions, verbal fluency, attention, memory and learning. It is becoming increasingly apparent that many children with bipolar disorder have particular difficulties in the areas of executive function: planning, strategizing, organizing, relinquishing a task and changing set, and other related mental skills.

The cognition-improving benefits of the atypical antipsychotics, as well as all the benefits mentioned above, make the fight against weight-gain worth mounting. Naturally, we hope for better medications that have lesser complications. But for now, the available atypical antipsychotic drugs are the best we have, and with knowledge aobut them comes protection from their adverse effects.

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We’ll write again soon.

As always, we look forward to hearing from you and send you and your children our very best,

Janice Papolos and Demitri F. Papolos, M.D.

References:

Allison DB, Mentore JL, Heo M, et al.: Antipsychotic-induced Weight-gain: A Comprehensive Research Synthesis.” American Journal of Psychiatry 1999; 156: 1686-1696.

Breier, A. Y. Tanaka, et al. “Nizatidine for the prevention of olanzapine-associated weight-gain in schizophrenia and related disorders: A randomized, controlled, double-blind study.” Presented at the 41st Annual Meeting of the New Clinical Drug Evaluation Unit, Phoenix, AZ, May, 2001.

Faedda Gianni L, Ross J. Baldessarini, et al. “ Pediatric-onset Bipolar Disorder: A Neglected Clinical and Public Health Problem.” Harvard Review of Psychiatry 1995; 3: 171–195.

Gallhofer, B., S. Lis, et al. “Cognitive dysfunction in schizophrenia: A new set of tools for assessment of cognition and drug effects.” Acta Psychiatr Scand 1999; 99 (Suppl 395): 118–128.

Gelenberg, Alan ed. Biological Therapies in Psychiatry 2001; 24 (November).

Goldstein, Lee E., and David Henderson. “Atypical antipsychotic agents and diabetes mellitus.” Primary Psychiatry 2000; 7: 65–68.

Henderson, David C. “Clinical experience with insulin resistance, diabetes ketoacidosis, and Type 2 diabetes mellitus in patients treated with atypical antipsychotic agents.” Journal of Clinical Psychiatry 2001; 62 (Suppl 27): 10-14.

Lebovitz, Harold E. “Diagnosis, Classification, and Pathogenesis of Diabetes Mellitus.” Journal of Clinical Psychiatry 2001; 62 (Suppl 27): 5–9.

McIntyre, Roger S., Deborah A. Mancini, and Vincenzo S. Basile. “Mechanisms of antipsychotic-induced weight-gain.” Journal of Clinical Psychiatry 2001; 62 (Suppl 27): 23–29.

Meyer, Jonathan M. “Effects of atypical antipsychotics on weight and serum lipid levels.” Journal of Clinical Psychiatry 2001; 62 (Suppl 27): 27–34.

Rossi, A., F. Manicini, et al. “Risperidone, Negative Symptoms and Cognitive Deficit in Schizophrenia: An Open Study.” Acta Psychiatr Scand 1997; 95: 40-43.

The authors would like to thank Catherine Schwartz, Lynne Brody, M.D., Richard Hauger, M.D., and Ross J. Baldessarini, M.D. for their assistance in preparing this article.

We can’t open up this newsletter without first acknowledging the devastating events of September 11th. The magnitude of this disaster is almost beyond comprehension and we hope you and your children are weathering the multiple traumas that began so unexpectedly that late summer morning.

New York City is a very changed place now: No horns honking, the pace has slowed, and the grief is palpable. Everywhere you go, people are reaching out to each other. Even riding an elevator is a different experience. No one stares up at the floor buttons anymore; people are engaging each other instead. The other day a New York City fire truck careened down Broadway with five firemen on board and half the street froze. If it’s possible to silently telegraph a message of profound sympathy and respect to human beings passing by, than we all surely did.

One of the ways we’re hoping to move forward from this tragedy is to concentrate on people who are builders, not destroyers. This edition of the newsletter will focus on two parents and the school that they founded to serve the needs of children with bipolar disorder and their families. Four years ago, Glad and Richard Curlee opened the Austin Harvard School, in Austin, Texas, the first school in the country with this specialty. Demitri was invited to speak there the first week in October, and--based on his visit, the written correspondence of the parents whose kids attend there and notes from the children themselves, and extensive interviews with Glad and Richard--what they’re doing there seems to work. The children have very high attendance records (they rarely miss school unless they are physically ill) and they are happy and learning.

Glad and Richard graciously shared their experience and expertise with us, as parents and educators in other parts of the country could use this as a model or adapt a few of their techniques and philosophies in the schools their children are attending.

School: A Child’s World Beyond Home

No part of a bipolar child’s life is more difficult to fathom than the piece called “School.“ Parents are never sure how much to reveal to a school system, they are spending inordinate amounts of time learning the laws of IDEA and trying to perfect IEPs, and the phone becomes an instrument to be feared as it rings too often with the school personnel calling to say “Please come pick up your child. He’s having a problem and we can’t control him.” Almost all parents anxiously scan the faces of their children each morning to assess whether the day is going to be a bad one and whether it might be wiser to let the child stay home. Exposing the child to stress is risky and he or she might end up in trouble and reveal problems to classmates and teachers. Yet the child must get an education, and certainly wants to be like all the other kids.

Glad and Richard had this problem with their two children who were diagnosed with ADHD and possible bipolar disorder early-on. Her mornings were spent trying to peel her son off the inside handle of the car (and then from the outside handle immediately after) in order to get him into the school building. She and Richard thought about home schooling, but since Glad is a licensed marriage and family therapist, she decided to start a school because, as she said: “I wanted my children to succeed in life and I wanted others to succeed with mine.”

In December of 1996, her school became a 501(C)3 organization and opened its doors with 11 children (the school is K-9). “That first year, we thought we were an ADHD school, but the majority of the kids had mood swings and were actually undiagnosed but truly bipolar,” Glad told us. Although they initially started with certified teachers, they found out that the children seemed to learn better with a CD-ROM program called Switched-On Schoolhouse. I asked her why.

This kind of curriculum focuses them. Each student has a carol and a computer with headphones, and the curriculum is visual, auditory, kinesthetic, and allows each child to progress at his or her own speed. Because the curriculum is rich and comprehensive, our teachers don’t have to spend as much time doing lesson planning and grading and they can deal with each child’s behavioral and emotional issues.

Switched-on Schoolhouse is a Christian values program, and each grade level comes bundled with a Bible study section (Austin Harvard doesn’t use this and has children of all religions in the school). There is no proselytizing as that their mission is to teach children with bipolar disorder to learn and to fulfill their potential. Period. “It’s simply the best program out there,” said Glad.

I called Alpha Omega, the producers of Switched-On Schoolhouse in Phoenix, Arizona and spoke with Nancy Halle. I asked her to explain their curriculum and tell me something about it. Her discussion and the demo materials she sent us showed that Switched-on Schoolhouse’s curriculum is an advanced multi-media-based learning environment. It incorporates video clips, sound files, animations, computer games, drills and tests. Nancy said that they’ve heard that ADHD kids do well with the program because they can see it, hear it, and touch it, and it focuses learning. The student can turn it on and off as attention waxes and wanes, but any work that the student skips or fails to answer correctly comes up at the end so he or she can’t move on until the lesson is mastered. This way, no child’s lack of learning “slips through the cracks.”

This system even grades tests and records them on the student’s file and lets the teacher know how long the student spent on each subject, so the teacher can see how quickly or slowly the student is grasping that subject. An extensive diagnostic test which is part of the program tells the teacher the child’s true level and identifies strengths and weaknesses the child may have, or where the holes in the child’s education are at that particular point in time.

One mother explained one of the values of a computer curriculum for bipolar children and how Austin Harvard uses this program to accommodate her son’s illness. She said:

He missed the first two weeks of school due to his illness. When he came back, they simply rearranged his planner and let him get started like he hadn’t missed anything. That is another advantage of the computer-based curriculum for these kids: It can be self-paced and tailored to the needs of the child. The child is not allowed to slack off, however. The teachers decide where he or she is supposed to be at in the curriculum and that is put into the child’s daily planner. The student is expected to keep up with this plan, but it can be modified according to need.

More than one million children are home schooled and using home schooling books, CD-ROMs, Internet sites, etc. We searched for other curriculums and found that William Bennet’s K12 program offers only grades one and two, and we looked at a few other programs, but nothing came close to the excitement and richness of Switched-On Schoolhouse. We are, however, sensitive to the fact that the religious content woven sporadically through the text may be an issue for some parents. However, after reading an October 12th Wall Street Journal article about Christian children attending Jewish Day Schools and Jesuit Academies observing Yom Kippur, we’ll mention the fact and leave it there.

A Day At Austin Harvard

Austin Harvard has a dress code of sorts--one uniquely suited to children with bipolar disorder and their sensory issues. Glad decided that since these children are difficult to get up in the morning and often have difficulty deciding what to wear, she would keep things simple: There is a teal Austin Harvard collared shirt. For those kids who cannot tolerate collars, there is a teal Austin Harvard T-shirt. (The kids voted on the color.) They can wear jeans, shorts, pants or skirts with the shirts. Because Glad understands that some kids cannot stand “nubbies” on socks, socks are not required except on days they have gym.

The day begins with a half hour “Devotion” which is a practical lesson about life. It typically is a story with a point about a good choice or an inappropriate choice. This is an interactive discussion that goes on for 30 minutes. “This time lets them wake up or calm down,” Glad told us. “At 8:30 they go to class.”

There are two classrooms: the five-to 11-year-olds are in one classroom; and the 12-15-year-olds are in the other. There are two teachers, and Glad and Richard, and the school’s outstanding Principal, Kim Belknap, travel between the classrooms. Parents come in to help also. When I questioned Glad about the age span of the kids in the same room, she said: “Many of our children are somewhat immature and they feel comfortable with younger children. Also, the older children feel competent and help out the younger ones. It fosters a sense of community.”

Each child has a carol/work station and each child has an ongoing planner. Usually they start out with math, but if a child has language problems, he or she starts with that. The children tape record all their lessons and answer questions about the lessons on paper so that they learn writing skills. Each student is assigned a partner and the two monitor one another. When they are at their computers, the kids can only talk if they raise their hands. Each academic class runs for 40 minutes, and there is a warning given ten minutes prior to the end of each class to prepare the students for a transition.

If a student finishes all of the work, there is no homework (unless he or she has blown off the school day). The only after school assignment is studying for quizzes and tests. One of the parents at the school wrote us and said: “If our son applies himself during his work day, homework is basically test prep. If he chooses to ‘blow off’ a day, he’ll have to work at home. I do think the school is sensitive to the issues which occur in the late afternoon when stimulants wear off.”

There is a Social Skills class taught two times a week by a licensed professional counselor where various subjects are discussed. When I asked Glad for an example she answered: “We’ll discuss lying. Why do people choose to lie? The children are always being taught that there are inclinations and choices; good choices and bad choices. We also spend a lot of time talking about anger. She expanded on this:

When we’re scared, we often get angry, but when we get angry, we give away our personal power to someone else. We go through a process that helps them identify what they’re angry about and what they can do to win? How can they maintain control but still get their point across to the other person? We suggest ideas such as talking calmly or taking a time out for a few minutes and then re-approaching the situation and telling the person how he or she feels. I always tell them I want them to feel appropriate control of themselves in a situation. The children offer solutions to each other and thus they learn the tools themselves.

The kids have science lab, and art, gym at the nearby Y, and every Friday is a field trip relating to the work they’re doing. For instance, the 7th graders in Texas study the history of their state and they make trips to the Alamo, and to the frontier village of Gonzales to watch the reenactment of the Battle of Gonzales.

Because so many of the children have co-morbid learning disabilities, there are methods of remediation customized to each child. Glad explained:

If the child is dyslexic and needs assistance we often take them through the Stevenson Language Program. We also use the clay techniques explained in the Davis “Gift of Dyslexia Program.” Since our curriculum is computer based, this helps our dysgraphic students. We do scribing as needed. We use manipulatives and Semple Math. Writing or taping the math steps for a given concept and allowing the students to review them before they begin their lessons is a great help.

The school’s philosophy is that each child has a learning style and the teachers want to help the student discover how he or she learns best. One child may discover that he or she can benefit from the use of a “white noise” machine to block out distractions, while another may learn that he or she actually absorbs verbal instructions best while doodling on paper. But once a child discovers his or her personal learning style, the child will be able to effectively use that knowledge to shape the way he or she approaches future educational pursuits. One mother wrote us that: “We have discovered that our son is an auditory learner, but the best part was when he realized it himself last year.”

Behavioral Issues

Austin Harvard uses a token system for good behavior and a consequence system for behavior that is not productive. If the student stays on task, has a good recess, or participates in Devotion, than he or she receive tokens. For every subject that is finished, the student gets 10 points. They are each working toward 100 points a day and if the student earns even 50, he or she gets to buy something in the school store and gets free time or an extra art class. A chart is kept on the door each day.

If a child begins to feel anxious or over-stimulated or begins to feel a rage gathering, he or she has several options. There is a lunch room the child can go to; there is a punching bag he or she can use to work out some aggression in a safe, private place. Rarely does a child need to go home. “Unless a child needs hospitalization, we keep them in school. Missing school is not preparing them for the real world,” said Glad.

If a child’s behavior is not up to the standards set, he or she is typically given a consequence. This is more likely than not an assignment where the student has to write sentences over and over again. “They hate to write,” Glad said with a laugh, “ so they tend not to go there. Sometimes they’re assigned push-ups, but they always learn that certain behaviors are acceptable and certain are not.”

Demitri observed the classrooms for a few hours on a Friday morning and he was very impressed with what he saw. He told me:

All the children seemed engaged in the learning process. They seemed able to concentrate and work independently. They raised their hands when they had questions and a teacher or adult in the classroom attended to their questions.

During the time I was there, two or three students disengaged and became a bit disruptive. They were immediately confronted, the disruptive nature of the behavior was explained and they were offered a choice to leave the classroom and calm down in a “safe place,” or he or she would be given a consequence (one boy was actually assigned to run up and down the hallway 20 times but it seemed to relieve some tension for him).

The school is well-organized and the authority structure is well-deliniated. The children are never allowed to commandeer the situation. At the same time, everything is handled compassionately.

One mother whose son is a student at Austin Harvard wrote us that:

It’s the social-emotional child that concerns me. We chose AHS for many reasons, but perhaps the most important would be the constant social skills, consistent approach to discipline, attention to ‘people skills’ which will help prepare my 14-year-old for the real world. He has (in the past two-and-a-half years) already developed many coping strategies and anger management techniques which give him control. He’s being given every opportunity to become a happier, healthier teenager.

The philosophy at Austin Harvard is to work very closely with the parents and the children. The parents report troubles at home to the Curlees instead of hiding them, and--as a team--they attempt to work through the problems. One girl had a rage one night because she didn’t like the sandwiches her mother was preparing for her lunch. They discussed it with Richard Curlee who acted as a mediator and he got the student to agree to take responsibility and make her own lunch every day. “We don’t want to be an RTC,” said Richard Curlee, “because after a child returns home from one, the family hasn’t developed skills to cope with the child and the illness. If we work with the family, supporting them and dealing with the many issues, it’s a 24-hour learning environment and families eventually get to be families.”

The medical aspects of the child’s illness are well-attended to also. As the Principal, Kim Belknap explained:

Before each visit to the psychiatrist, we generate a report covering anything that needs to be addressed. Our parents have come to rely on and appreciate the importance of our input. When the doctor is unwilling to receive the input from us, the parents use the report information and act as a go between.

She continued:

Our reports help the doctors and therapists who are treating the children get a good picture of the child’s functioning at school, and help the doctor assess whether the child is stable or not. He or she can then make changes in medication regimens to increase stability or ward off possible breakthrough episodes.

Tuition and Other Practicalities

The tuition at the Austin Harvard School is $5500 a year. For some of us who just learned that New York City nursery schools cost $15,000 a year, this doesn’t seem like a lot of money. Richard Curlee did tell us that each parent is expected to help raise $4500 through fundraising efforts, or pay the difference. They have different kinds of fund raisers throughout the year and all the parents help out.

The parents must spend eight hours a semester helping out in the classroom, and there is a mandatory meeting one evening a month.

The school is a storefront building set up with a waiting room, two classrooms, a lunchroom that doubles as an art room, three offices and a bathroom. The actual square footage is 2300 square feet. (Recess is held at a park nearby.)

Because Austin Harvard is young yet, and because the school requires that children with bipolar disorder be on medications, it is not accredited (with the exception of the ninth grade). When we asked how students do after Austin Harvard, Glad told us that one of their students just went on to eighth grade in a public school and is doing very well. The school is only four-years-old, so each year will see more children making the transition and we’ll report outcomes as we learn of them.

How Do Students Feel About Austin Harvard?

One mother answered the question “Is your child happy attending Austin Harvard?” with the statement: “He started last year right after the spring break and really struggled with the discipline, but during the summer all he did was talk about going to school again.”

One boy handed Demitri a written account of “Why I Want to go to the Austin Harvard School.” In it he explained:

I think they can help me with my frustrations with studying. The teachers also teach you discipline and cooperation with students, they also teach you how to express yourself without hurting anyone. Mr. Curlee, the Dean of the school is very funny but very strict. I like him and respect him very much. I also respect the teachers and the principal, Mrs. Belknap, and the founder of the school Mrs. Curlee.

The nice thing about the school is the teachers teach with computers and audio and visual tools. Instead of writing things down all the time, you get to use a computer and tape recorder.

I expect to learn all kinds of skills at this school--like computer skills, expressing my feelings, learning respect, learning how to help others, learning how to cooperate, learning how to communicate feelings so they can be solved, etc. If I can do these things, I can do anything I want to. I’ll just remember the two rules Mr. Curlee explained to me: “I love you and there’s nothing you can do about that.”

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We want to applaud Glad and Richard Curlee for pioneering a way to teach children with bipolar disorder and for having the vision and the dedication to make a difference in the lives of these children and their entire families. It is hard to believe that they accomplish all this with a budget of $200,000.

We asked the Curlees if they might consider conducting workshops and showing other motivated parents how they’ve done all this, and they said they would welcome inquiries. Contact Richard Curlee at the web site of the school www.austinharvardschool.org.

For more information about the computer program, Switched-On Schoolhouse, visit www.aop.com. Nancy Halee said she would be happy to answer any questions, also. She can be reached at (602) 438-2717, ext. 7929.

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We began this newsletter by discussing a deep desire to move forward from tragedy at a very shaky time. Writing this newsletter helped me more than you can know. Thank you for being out there.

The work continues, and Demitri and I would like to take this opportunity to formally announce the launch of the Juvenile Bipolar Research Foundation. This will be the first charitable foundation to focus its energies and funding solely on research for the causes, treatments, and prevention of childhood-onset bipolar disorder. We are excited about this new venture and would be happy to provide you with more information. Our web site is under construction, so contact us here at http://www.bipolarchild.com, or contact our President, Tina Fay, at jbrfinfo@aol.com.

We’ll write again soon. In the meantime, may you and your children experience physical and emotional well-being during these very tumultuous days. From our home to yours, we wish you peace.

Janice Papolos and Demitri Papolos, M.D.

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The authors wish to thank the parents and students of the Austin Harvard School, Nancy Halle of Alpha Omega Publications, and, most especially, Mary Jane Hatton and Sandi Norelli who composed a list of in-depth questions based on their extensive knowledge of the educational issues for bipolar children.

If a parent and a doctor were to dream up a wish list mood stabilizer for a child suffering with bipolar disorder, it would be extremely effective without major side effects, it would work against aggression and rage, it would prevent future episodes of illness, it would require no systematic blood draws, and it would not cause weight gain, liver toxicity or aplastic anemia.

An anticonvulsant launched in this country a year ago February (but used in the pediatric epilepsy population since 1990 in Europe), seems to hold a lot of these cards upon early examination, but much is still left to be seen. It is called oxcarbazepine and is marketed in this country by Novartis under the brand name, Trileptal.

Actually, Trileptal is an analogue of Tegretol (carbamazepine). An analogue is structurally similar to another compound, but differs slightly in its composition (such as replacing one atom by another atom of a different element).

Someone in the Ciba-Geigy labs in Switzerland, played around with the carbamazepine compound and added one oxygen molecule to the top of the middle structure. What a difference an oxygen atom can make: Whereas carbamazepine oxidizes in the body into an active metabolite called 10,11 epoxide, oxcarbazepine rapidly converts in the body to 10-monohydroxide derivative (MHD).

chemical structure and metabolism of oxcarbazepine vs. carbamazepine

Carbamazepine (Tegretol) is an effective mood stabilizer for bipolar disorder, but it seems that the 10/11 epoxide metabolite is responsible for some of the major problems that can occur with the drug.

As we write in The Bipolar Child, "because Tegretol activates certain enzymes in the liver, and this causes the drug itself and many others to be metabolized faster, the serum Tegretol level may drop somewhat after the first month of treatment, requiring increased doses based on blood levels." Therefore, blood levels are needed more frequently in the beginning of treatment and every three months or so afterward. "(Anecdotally, we have heard of many instances when blood levels have dropped--particularly in young children--multiple times with successive increases in dose due to this enzyme induction.)

This induction of the liver enzymes is a result of the 10,11 epoxide metabolite. In contrast, the principal metabolite of Trileptal's (MHD) has little effect on liver enzymes, so that its own serum levels remain fairly constant. Moreover, unlike Tegretol, it is less likely to increase the rate of elimination of many other drugs.

There have been several reports of bone marrow suppression (aplastic anemia) with Tegretol. While very rare, this is a life-threatening condition. Even less likely are suppression of the formation of blood platelets required for forming blood clots, and white blood cells that fight infection. Therefore, it is good medical practice to have a complete blood cell count regularly at the beginning of treatment and each time the patient develops any signs of easy bruising, and certainly if the triad of fever, sore throat and rash develop in combination.

Evidently because of its different metabolism, Trileptal is much less likely than Tegretol to cause aplastic anemia. In addition, liver toxicity occurs rarely with Tegretol, but is unknown with Trileptal.

Although Trileptal has less risk of drug-to-drug interaction than Tegretol, it can increase the rate of elimination, and reduce the effectiveness of some drugs--notably oral contraceptives (parents of adolescents, please make note!) and one calcium channel blocker, in particular, Felodipine. Therefore, Trileptal may be safely combined with Lamictal, Depakote, and lithium, as well as with antidepressants and antipsychotic medications.

Sounds great so far, but you must be thinking: What are the side effects of Trileptal and how well does it work?

The Side Effects

Adverse side effects that may occur early in treatment with Trileptal are sleepiness (somnolence), headache, dizziness, double vision, ataxia (unsteadiness), vomiting, rash, and abdominal pain. Most of these side effects--should they occur--recede as the body adjusts to the drug in a few weeks. We have heard of a case of sun sensitivity caused by the drug (not surprising because Tegretol can cause this also).

There is a drop in sodium levels (hyponatremia) in 3% of those taking Trileptal. Therefore, a baseline lab test should be done on all patients before the drug is started, and children with sodium levels below 135 mEq/L should be watched more closely. Hyponatremia is rare in children, but teenagers who may ingest diuretics surreptitiously for weight loss are at risk, and this should be explained to them at the beginning of treatment.

Hyponatremia can be treated easily and it is recommended as a general practice that every fourth drink should be a sodium-containing one such as milk or Gatorade. Milk has 125 grams of sodium in an 8-ounce glass, and Gatorade has 115 mg of sodium in an 8.45-ounce juice box.

Symptoms of hyponatremia include not passing much urine, headache, confusion, tiredness, and, if very severe, seizure and coma. Because Trileptal has been shown to be very effective in the treatment of partial seizures, it is FDA-approved as a monotherapy for epilepsy in adults, and approved for children age 4 and older as an add-on anticonvulsant. Therefore, we already have studies showing its safety in the pediatric population.

How Well Does Trileptal Work in Bipolar Disorder?

Several studies have evaluated the effectiveness of Trileptal in acute mania. In 1983, Dr. Hinderk M. Emrich of the Max Planck Institute in Munich performed a double-blind, placebo-controlled study using oxcarbazepine, and found an average change of 50% in the mania scales was achieved by the use of this medication. As a consequence of these findings, Ciba-Geigy of Basel organized two multi-center studies using oxcarbazepine. One compared oxcarbazepine with the antipsychotic drug, haloperidol (Haldol). After two weeks, both treatments (haloperidol and oxcarbazepine) were about equally effective in the 58-patient study, on the basis of decreasing mania-scale scores.

Another international study compared the anti-manic effects of oxcarbazepine to lithium. Again, after a two-week period, the drugs were found to have about equal efficacy for the treatment of acute mania.

This past May, Michael Reinstein, M.D., an Assistant Professor of Psychiatry at Rush Medical Center in Chicago, presented a poster at the American Psychiatric Association's annual conference, in which he compared Trileptal to Depakote in the treatment of mania and found them to be indistinguishable in both efficacy and tolerability of side effects in adults.

How well does Trileptal work as a maintenance medication? To date, no drug but lithium has been approved for the prevention of episodes of mania in bipolar disorder, and none is approved for preventing recurrences of bipolar depression specifically. Nevertheless, Tegretol and Depakote are used routinely for these purposes and often seem to do the job well. We have only anecdotal information about prevention of episodes and future stability with the use of Trileptal, but when we asked Dr. Reinstein if he had noticed a preventative quality and how long he saw stability he answered: "We have been using Trileptal a little over a year now and we are very impressed with the stability we've seen in the patients. It has become the first line of treatment in our clinic for our patients with bipolar disorder." Dr. Reinstein also spoke of the effect Trileptal has on the aggressive behaviors of the children he's seen. He said: "When the dose gets high enough, the aggression tends to subside."

We next interviewed Dr. Boris Rubinstein, an Assistant Clinical Professor of Psychiatry and Pediatrics at Columbia University's College of Physicians and Surgeons in New York City because he has treated a number of children with Trileptal. While he doesn't yet use it as a first-line treatment, he told us he was impressed with its mood stabilizing effects and--while cautious-- said that :"In my initial assessment, I am very enthusiastic about Trileptal."

He feels that it may well turn out to be a particularly useful drug for children and spoke of the difficult-to-assess four-year-olds who present with ADHD and a lot of aggressive behaviors. "If these are budding bipolar children, I would feel comfortable starting with Trileptal," he said. Unlike stimulants or antidepressants, this option would not exacerbate a possible bipolar disorder.

Much remains to be learned of Trileptal's efficacy in the treatment of early-onset bipolar disorder, and whether or not it is an effective long-term maintenance treatment, preventing future episodes of cycling. Studies are in the planning stages to answer these questions. It is also important to emphasize that Trileptal is officially recognized by the FDA as an anticonvulsant, and that all use in mania or to prevent recurrences of bipolar disorder are to be considered empirical and "off-label," based on individual clinical decisions by a physician.

Dosing

Trileptal is supplied in 150, 300, and 600 mg tablets scored so that they can be cut in half. In addition, there is a lemon-flavored oral suspension for children who have difficulty swallowing tablets. The liquid preparation is palatable to children (we haven't tasted it, however). It must be shaken well before given to a child. It is supplied at a concentration of 60 mg/ml, or 300 mg per 5 ml teaspoon.

Children are typically started at 300 mg per day--in divided doses--150 mg in the morning; 150 mg approximately 12 hours later. The manufacturer's recommendation is to raise the dosage every 7 days in increments of 300 mg (again the 300 mg increases are best divided into two-a-day half- doses) with a target dose of approximately 900 mg to 1200 mg (some children may require as much as 1500-2400 mg).

The drug reaches a steady state, or stable, concentration in the blood stream after about 4 doses or within two days. One mother whose 11-year-old son was cycling wildly throughout the day (despite his being on Clozaril and Zyprexa) wrote of her son's experience with Trileptal: "At about three weeks, as his dose was 900 mg, we began to see the amplitude of his mood swings diminish. At 6 weeks and 1200 mg, the cycling practically stopped. Since no other medication was added at this time, we're sure the Trileptal smoothed out the cycling pattern."

This young man has now been on the medication for a few months and continues to do well, but--as we said above-- only time will tell if the drug is effective as a long-term maintenance mood stabilizer.

Serum Levels of the Major Trileptal Metabolite (MHD)

A blood test is available to monitor the serum level of MHD (monohydroxide derivative), but the clinical value of this measurement is uncertain. At this point the blood test might be useful to ensure that an adolescent is taking the medication--more of a measurement of compliance, so to speak, whereas dosing is better guided by clinical response and tolerability by individuals.

The Cost of the Medication

Trileptal is expensive--about $1.50 for a 300 mg tablet, with only moderate increases in cost-per-pill for larger quantities. If a child takes 1200 mg a day, then a one-month supply will cost about $150-180. A 2400 mg per day regimen could cost nearly $300 a month.

As we wrote in The Bipolar Child (page 128), "Everyone should comparison shop for medications. The same medication in three drugstores in the same neighborhood can have three very different prices. Also, purchase the largest-size tablet or capsule available, consistent with the dosage prescribed." (A patient taking 1200 mg of Trileptal would pay less for two 600 mg tablets than for four 300 mg tablets.

For families that don't have prescription cards or funds to pay for Trileptal, Novartis runs a program that will supply the medication for free. It can be applied to by the treating physician.

In Conclusion

Naturally, we wish we could give you more information about Trileptal, but we are hopeful that-- for some children--this is a new ally in the fight against this dreadful illness. Because Trileptal's safety profile in children is promising, its levels don't fluctuate due to liver enzyme induction, it requires few blood draws, and it doesn't cause the distress of weight gain, it is a welcome new tool in the psychiatric armamaterium; another option on the table.

We also hope that Trileptal's safety profile will help doctors feel more comfortable making the diagnosis of early-onset bipolar disorder and treating the illness at an earlier age, thus saving the child and the family the chaos this disorder engenders. Perhaps fewer doctors will adopt a "wait-and-see" attitude because they fear possible adverse effects from mood stabilizers.

However, we want to make the point clearly that if your child is doing well on Tegretol, Depakote, lithium, etc. it is unwise to change the regimen because you read about a new drug or supplement. No one drug works for every child, and these other mood stabilizers have known advantages (for instance, there is emerging evidence that lithium has a strong and possibly unique effect against suicidal behavior and is neuroprotective as well). If your child is stable, do nothing to rock that blessed boat.

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Bibliography
Dunn, Robert T., Mark S. Frye et al. "The Efficacy and Use of Anticonvulsants
in Mood Disorders." Clinical Neuropharmacology 21 (4): 215-235.

Emrich, H.M., M. Dose, and D. von Zerssen. "The Use of Sodium Valproate,
Carbamazepine and Oxcarbazepine in Patients with Affective Disorders."
Journal of Affective Disorders 8 (1985): 243-250.

Papolos, Demitri, and Janice Papolos. The Bipolar Child. New York: Broadway
Books, 2000.

Reinstein, Michael J. John G. Sonnenberg, Sangarapillia C. Mohan, Maxim A Chasanov et al. "Comparative Efficacy and Tolerability of Oxcarbazepine versus
Divalproex Sodium in the Treatment of Mania." A Poster presented at
The American Psychiatric Association Conference, New Orleans, 20001

The authors wish to thank, once again, Ross J. Baldessarini, M.D. for his abiding interest and expertise.

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As a final note, we'd like to point out two non-Trileptal matters: For our Texas readers who have asked when Demitri will be speaking in their state, save October 3rd and 4th, 2001. He will be speaking in Austin under the sponsorship of the Austin Harvard School for two-full-day workshops. Since this is one of only two schools in the country set up specifically to teach children with bipolar disorder and ADHD, we will report on the school's philosophy and curriculum in our next newsletter. (Find out all the details under "Workshops" at http://www.bipolarchild.com. )

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RESEARCH SURVEY
We are conducting a survey having to do with carbohydrate craving and temperature regulation in children diagnosed with bipolar disorder, and hope that you will find the time to help us in this research effort. The questionnaires shouldn't take more than 15 minutes to complete. In addition, we would ask you to measure your child's body temperature with an oral mercury thermometer at 4 specified times within a 36-hour period.

If interested, below, you will find links to four separate RTF files:

• Instructions for the study
• The food cravings and thermoregulation survey with answer sheet
• The Bipolar Child Parent Questionnaire
• The body temperature recording sheet

Each of these files has instructions that will hopefully allow you to complete the survey without difficulty.

Please open (1) Instructions for the study first. This document explains the steps that are required to complete the survey.

As soon as the findings are published in the psychiatric literature, we will discuss them in detail in a future newsletter. Thank you so much for considering participating in this study!