This is the last of a three-part series to inform you about the findings from research studies funded by the Juvenile Research Foundation. The first two Newsletters described the approach and development of a new perspective on pediatric bipolar disorder. This Newsletter tells you about the direction that researchers plan to follow now that the foundation for this novel view is in place. We hope you will be encouraged by the progress and inspired to believe that the end of this journey is attainable.

The research that we have brought to your attention is well poised to move on to the next phase of investigation. The specificity and accuracy with which a subtype of the illness has been defined improves the chances of success for ensuing studies. To summarize the work to date, researchers supported by the Juvenile Bipolar Research Foundation (JBRF) has collected clinical information on a large sample of children who have been diagnosed or are suspected of having pediatric bipolar disorder. Multiple analyses run on this data generated the following:

• The delineation of a genetically robust trait called Fear-of-Harm (FOH) that serves to define a subtype of the illness which has become the focus of our investigation.
• A highly specific dimensional symptom profile that accompanies the FOH trait.

This highly heritable trait makes it an ideal candidate for further genetic study and the dimensional symptom profile points us to very specific brain pathways that may explain the biological underpinnings of this subtype. The dimensional symptom profile also allows us to identify, with 96% accuracy, children who have the trait. This is an enormous improvement over the current state of affairs and finally moves us down a path that could potentially yield more targeted treatment strategies, including pharmacological, psychological and circadian approaches.

To continue to focus on this single, hereditary behavior as the basis for future studies undoubtedly leaves some children who exhibit a bipolar disorder out of the mix. However, given the complexity of the physiology involved, this dissection of the illness into a very specific slice is necessary. This is the route that may better enable researchers to uncover real and useful answers.

This single behavioral trait is not uncommon. Some degree of the FOH trait was found to be present in 2/3 of the study population. A full 1/3 of the subjects exhibited the trait in its pure form. So, while it does not cover all children, it is very relevant and conclusions drawn from it are likely to have wide application.

The compilation of evidence-based not conceptual information is key to the development of a broad-based body of knowledge that can move the research agenda forward. Listed below are the three main research areas that researchers now plan to pursue as this strong foundation of inquiry has been established.

Genome-wide Association Study

Identification of susceptibility genes for bipolar disorder is the most direct way to discover the network of signaling pathways in the brain that regulate specific behaviors associated with the condition. The development of treatments which specifically target those pathways can then be launched.

In a technique called genome wide association study (GWAS), investigators scan the entire human DNA, or genome, of many individuals to pick up genetic variations that differ between healthy individuals and individuals with the disorder of interest.

Of critical importance to the success of this approach is: 1) the selected cases should be homogeneous for the target condition, and 2) the sample size must be large enough to provide statistically significant results.

We believe that the delineation of the FOH trait and the dimensional, clinical profile of symptoms associated with it will potentially allow us to gather such a homogeneous group. The ease and accuracy that the Child Bipolar Questionnaire brings to the identification of children with the FOH trait promises to round up the very large sample of cases needed to proceed with the scan. JBRF has already made substantial progress in the process of collecting DNA samples from children who fit the FOH trait. We need your participation to gather as many samples as possible. A link for this purpose is at the end of this News Flash.

Chronobiology Biomarker Study

Chronobiology is the study of biological rhythms. A biomarker is a distinctive biological indicator of a process, event, or condition. The identification of a biomarker for a specific condition greatly enhances diagnostic reliability and simultaneously identifies a treatment target that may reduce the impact of the condition. In this study, investigators seek to explore the relationship between sleep/activity patterns and thermal regulation in children with the FOH subtype to determine if some imbalance in the relationship between these rhythms could be a biomarker of the illness.

Preliminary studies and longstanding clinical observations tell us that many children at risk for, or who carry a diagnosis of, pediatric bipolar disorder experience numerous types of sleep disturbances as well as a dysregulation of activity rhythms. They also feel excessively cold in the mornings, overheat in the evenings, have a poor thermogenic response to cold, and sweat profusely during even mild physical exercise. Dimensional analysis revealed that these phenomenons are represented as parts of behavioral dimensions that accompany the FOH trait. Since we know that the relationship between core and outside body temperature interact with the circadian rhythm of sleep, the onset and offset of sleep as well as the quality of sleep, the dysregulation of this relationship may well be a biomarker of the condition.

Investigators have launched a study, funded by the National Institute of Mental Health (NIMH), to explore this phenomenon. While the study is ongoing, preliminary results indicate that this could indeed turn out to be a biomarker for the illness. What's more, the underlying physiology involved in the core versus outside body temperature relationship also influences other dimensions of the illness such as anxiety, aggression, sweet cravings, and fear conditioning.

Stem Cell Study: Turning Skin Cells into Brain Cells

In a remarkable new process that is only three years old, investigators have the capability to deprogram a skin cell, return it back to its original stem cell state and then encourage it to develop again down a completely different developmental path into a brain cell or "neuron". This novel procedure will allow researchers to examine differences in gene expression in brain cells through a direct comparison of the DNA of an individual with pediatric bipolar disorder and a control subject.

This process could tell us all sorts of things about how that brain cell functions or malfunctions and how it will respond in the presence of different medications. Using the FOH phenotype to identify a clinically homogeneous group of children that represent a subtype of the illness, investigators are hopeful that they will achieve meaningful results.

We hope you have found this discussion interesting and inspiring. We feel that the research conducted so far has done a lot to correct a fundamental obstacle that prevented the timely progression of research and development. We look forward to the mounting body of useful information that this new approach opens up. Together we can find ourselves further down the path to peace that we and our children so desperately desire.

Alissa Bronsteen and Demitri Papolos, M.D.

This is the second of a three-part series to inform you about research on juvenile bipolar disorder sponsored by the Juvenile Bipolar Research Foundation.  We hope you will be encouraged by the progress and inspired to believe that the end of this journey is attainable.

What do the following have in common?

• deflects blame
• suffers horrendous nightmares
• antagonizes siblings
• excessively craves sweets and carbohydrates
• functions in mission mode
• wets the bed
• sleeps hot
• takes excessive risks
• hoards food
• has many ideas at once
• interrupts or intrudes on others
• experiences periods of self-doubt and poor self-esteem

Independently, each of these traits is a symptom of a myriad of different psychiatric disorders. Considered together, they are all symptoms of Pediatric Bipolar Disorder (PBD).

But wait a minute! Isn't bipolar disorder all about mania and depression? How can these unrelated symptoms be part of that same profile?

This more complete list of symptoms is reflective of the research progress JBRF has made by adopting the dimensional approach of defining psychiatric disorders: symptoms overlap between psychiatric conditions and one condition is differentiated from the other by how those clusters of overlapping symptoms come together.

Proceeding down this path, researchers have arrived at a novel perspective of the illness. While traits like mania and depression remain important, this analysis finds that they are not the central behavioral dimensions of PBD. Other dimensions such as aggression, anxiety, sensory sensitivity, sleep/wake disturbance, attention/executive function deficit, and oppositional behavior also figure prominently. Of paramount interest is a dimension that establishes a link between obsessive fears and aggressive behavior. JBRF investigators have termed this correlation "Fear-of-Harm" (FOH). This new characterization of PBD has been labeled the "Core phenotype".

The Core phenotype is a more complete and accurate description of what these children experience than what is offered by the Diagnostic and Statistical Manual for Mental Disorders (DSM). Investigators suggest that in the DSM, bits and pieces of this single disorder have been parceled out into numerous other diagnoses. It is likely that this fragmented perspective of the disorder has obscured a clear view of its actual presentation in children and stalled efforts to get at the underlying biology.

Concentrated exploration of the FOH trait has lead investigators to define a clinically homogeneous subgroup of children who are the most severely impacted by this disorder. This subgroup is called the FOH phenotype. These children are characterized by extreme anxiety and the hyper-perception of threat which causes them to respond in a defensively retaliatory manner. They are often hospitalized and face great challenges socially and academically.

Not only have research investigators been able to describe the symptom profile of this FOHphenotype, but under this new paradigm, they have also pieced together the likely underlying biology involved in the disorder. Certain brain areas, activities and development that had not previously been considered became obvious foci for their attention. The specific neural pathway that ties these activities together in a manner consistent with the profile has been identified. Investigation of this complex system is ongoing. The more the details fall into place, the greater its explanatory value grows.

The FOH phenotype moves us further in our quest to uncover the genetic variations associated with PBD. The high heritability of the FOH trait, refinement of the dimensionally derived symptoms that associate with it, and the fact that the CBQ can identify with 96% accuracy children whose profiles fit the phenotype make us optimistic that we are on the right path for a meaningful genetic analysis.

JBRF actively supports the collection DNA from children whose CBQ scores indicate that they fit the FOH Phenotype.

This novel understanding of the dimensions of bipolar disorder in childhood puts us on much firmer footing as we move towards the identification of biological markers. The identification of new biological markers opens the door for new treatments.

We are hopeful that this compelling work will facilitate the much needed consensus amongst researchers that will unite their creative minds into a common direction and thus enable us to move ahead more quickly on this journey towards relief.

Alissa Bronsteen and Demitri Papolos, M.D.

This is the first of a three-part series created to familiarize you with some exciting and hopeful information regarding research that has been conducted on juvenile bipolar disorder.

In order to get to the end of any journey, you must travel in the correct direction. In terms of understanding juvenile bipolar disorder, the The Juvenile Bipolar Research Foundation (JBRF) Research Consortium has taken some impressive steps down the right path.

The prevailing view of psychiatric illness has been that each mental disorder is unique and separate from all other mental disorders. As such, each behavioral symptom belongs solely to one or another of the identified illnesses. This is referred to as a categorical approach because each symptom is assigned to a discreet category. Practically speaking, all the diagnostic, clinical and research work of the last 30 years has used the categorical approach as its foundation. It is important to note that this foundation derives from ideas, not facts, and that the diagnostic categories it created were never intended to be permanent.

Psychiatric diagnoses do not have the benefit of biological evidence like medical diagnoses do. This is not surprising given the fact that our extraordinary brains and all-powerful DNA have, until recently, been pretty much beyond our reach to explore. Lacking biological evidence, ideas were the next best thing.

While the most passionate and well informed people were involved in the development of this approach, times have changed and knowledge has advanced. However, this underlying view has not. Fortunately, geneticists and neuroscientists have started to question the merit of the categorical approach to diagnosis. In fact, some investigators have reached the conclusion that this underlying framework may prove to be a principal obstacle that has led to stagnation of the research in the quest to untangle complex mental illnesses such as bipolar disorder.

"Big deal" you might say. It doesn't really matter what you call it or how you define it; what really matters is dealing with the individual's symptoms as they present. But it isa big deal; because the individual will never get relief until we can truly understand the problem. In today's cutting edge scientific practices, where microscopically small differences and enormously complicated mechanisms are in play, to start from a correct foundation matters.

The perspective that has emerged is that we need to study mental illnesses from the view that there is an inevitable overlap of symptoms between psychiatric conditions as they are now defined. What may distinguish one condition from the other is how those clusters of overlapping symptoms come together. This is called the dimensional approach to defining psychiatric disorders. Once this "new", more diverse profile of symptoms is established, the next step in the research process is to refine the profile in order to be able to link it to a specific biological source.

This dimensional approach is what the investigators of the JBRF Research Consortium have adopted. Proceeding down this path, researchers have arrived at a novel description of juvenile bipolar disorder that describes more directly and accurately the symptoms these children actually experience. This new perspective has quickly led to a model of the underlying biology that may help to explain this illness at a more fundamental level. It has opened up new research priorities and treatment opportunities. This view has led to the identification of a potential biomarker (measurable biological indicator) of the illness. Its accuracy makes the chances for meaningful genetic studies much more likely.

In the second part of this series, we will describe this profile in more detail and in the third part we will tell you what researchers are trying to do with this information. There are no answers that will turn your life around today. But we are confident that we are on the right path to provide those answers tomorrow.

Alissa Bronsteen and Demitri Papolos, M.D.

A few weeks ago, we listened to a radio broadcast produced by ABC Radio National in Australia whose topic was the diagnosis of bipolar disorder in young children. The segment begins with a send-up of the supposed American penchant for seeing psychiatric disorders everywhere. The listener hears a narrator intone: "You've heard about SARS, AIDS and bird flu. Now researchers from Australia claim we're about to be hit by a new epidemic: Motivational Deficiency Disorder." One of the symptoms of MDD is preferring to go to the beach instead of to work; at the most severe end of the spectrum, people are unmotivated to breathe and just die.

Jane Shields, the host of the show explains: "You might have guessed by now that this is not actually a genuine disease. It's a fictitious disorder created to show how easily normal behavior can be turned into illness.

"She then segues into the subject of the piece: the overdiagnosis of bipolar disorder in American children. According to a few of the doctors interviewed, this overdiagnosis is being driven by three factors: pharmaceutical companies looking to expand into the child psychiatric market, parents who don't wish to deal with their own failures, and doctors who can't be reimbursed by insurance companies if they don't assign very severe psychiatric diagnoses on claim forms.

We listened with dismay as Dr. Jennifer Harris, a psychiatrist who has worked in the inpatient child units of the Cambridge Health Alliance in Boston say: "I've probably seen only two, maybe three pre-pubescent kids who I was convinced had bipolar disorder..." The interviewer reported that "Dr. Harris has never herself diagnosed a pre-teenage child with bipolar disorder, and says it is very rare in children."

Dr. Harris' next comment:

There's been a move away from (Freudian analysis) towards a more biological model...and by "biological," I think people often mean "genetic." I think that focus on something more biological plays into parents' own desire to feel like they're not at fault, or it doesn't have to do with child rearing or something like that, or they don't want to feel like their child has a mental health condition; it's better to think that there's something biologically wrong.

Dr. Harris feels strongly that the insurance companies are instigating the push to make the diagnosis of bipolar disorder in children:

One of the things that happened is that people were no longer getting reimbursed from having more benign diagnoses...I don't get reimbursed for that (more benign diagnoses). On the other hand, if I put in a diagnosis of bipolar disorder, NOS, I get reimbursed. So bipolar disorder's got to be a more "serious" diagnosis and is much more easily reimbursed. I think this is part of what drives this...

By the time the show concludes, the listener has a mental image of parents bounding joyfully into the offices of child psychiatrists, only to be met by equally enthusiastic doctors holding prescription pads in one hand and a sheaf of insurance claims in the other. After a few preliminary questions, the doctors get down to business: confer the diagnosis and hand out a fan of prescriptions with little thought to the risks of such medications.

This discussion is absolutely insulting to doctors and the parents who must deal with very sick children. To accuse all physicians who have taken a Hippocratic oath to "first do no harm" of being lead around by the nose by pharmaceutical and insurance companies is irresponsible journalism.

Parents are not being lead around by the noses either. Bipolar disorder is the most genetic of all psychiatric illnesses, yet missing from the recent spate of articles and television segments is the fact that parents are likely to recognize the ominous symptoms early on because they experienced the feelings themselves as children, or because they lived with it long ago as a close family member manifested similar behaviors. They know the agony their child is experiencing, and while no one could help them years before, they are desperate to find help for their child today.

Mothers and fathers tell us stories of their children jumping out of second-floor windows, or out of cars, or running into streets. In the middle of almost-seizure like rages, they tear doors from hinges, break everything in the house, and pick up knives and try to kill themselves. Their behavior is dark and could not be mistaken for a typical high-spirited kid with attention deficit hyperactivity disorder (ADHD).

Parents have said to us over and over: "Do you have any idea what it's like to hear our seven-year-old say, 'I'm stupid, everyone hates me and I may as well be dead.'

"It is not uncommon for these children to hallucinate and experience delusions. Hardly the stuff of skits.

While certainly there has been a rapid increase in the diagnosis of the disorder, only fifteen years ago it was thought to be extremely rare and was therefore, rarely diagnosed. How much of this increase in the diagnosis is due to increased awareness and better diagnostic practice, or by environmental factors causing a rise in the incidence in the population is unclear.

What is clear is that this is not a benign illness--it warps children and it has a mortality rate greater than childhood leukemia. The lives of many of our youth are at stake, and the illness and its incidence requires research, not ridicule.

Contrary to what certain media pundits are putting across, many child psychiatrists in America do not believe children can suffer with the disorder, or think it is rare, or are not comfortable treating it. Since psychiatrists must diagnose using the psychiatric manual (the DSM-IV), and its criteria for children are derived from the adult form of the disorder (and a child's symptoms are very different), the demand that a child meet these more adult-like criteria make it difficult to make the diagnosis in children.

Compounding the problem is the fact that the illness rarely rides alone, but is often accompanied by symptoms that seem to represent attention deficit hyperactivity disorder, obsessional compulsive disorder, anxiety disorder to name the most common (see our November, 2006 newsletter, Why Is It So Difficult to Diagnose Bipolar Disorder in Children? at www.bipolarchild.com).

Until there are more specific criteria and genetic markers for the illness, the diagnosis will continue to be guided by the symptoms and behaviors of the children, the family history, and the psychiatrist's experience and level of expertise.

This is a wily illness. Parents talk about a child and his or her behaviors but this extreme, out-of-control behavior is rarely seen during an office visit, as the child works very hard to put on a good face to the outside world. He or she may be well-behaved and the doctor will see the true, sweet nature of the child, but once in the safe haven of the home, the need to vent often finds the child exploding and abusing the family--especially the mother. Unless a doctor recognizes the way this illness often presents in children, the doctor will find it hard to medicate a child who is not acting out publicly. (Sadly, this stark contrast between the office-and-at-home behavior leaves the parents feeling that the doctor may think they are exaggerating, or fear that he or she might be skeptical of their reports and think that they are somehow promoting the behaviors.)

No doctor likes to medicate a child. Child psychiatrists are acutely aware that the central nervous system is still developing and administering some of these medications in younger children can provoke paradoxical reactions (the opposite effect of what they're supposed to do occurs). They know that many of the medications are not approved for children with bipolar disorder (although many of the anticonvulsants are approved for seizure disorders in the very young, so there is a literature about these drugs), and they know the possible short-and-long-term risks.

However, those physicians with experience have seen lives restored to more normal pacing once the right combination of medications can be found, and they've had the experience of hearing parents say: "I've got my real child back. He was lost under all of this darkness."

As with all things in medicine, it often comes down to risk/benefit.

The Decision to Medicate

The journey that ends on the pharmacy line may begin with years of frightening incidents at home, expulsions from daycare centers, phone calls from concerned nursery school teachers, and long searches for a doctor who can tell the parents what is wrong and how best to treat it. Because it is a devastating journey for parents, with every step posing questions of risk and hope and heartbreak, we want to outline a few of those steps that many of the parents will face. The road to the pharmacy lines begin as parents are forced to:

• Look at a very young and much-loved child with a nagging fear that something is seriously wrong.
• Feel the external world bearing down on them, advising them to take multiple parenting classes or to tune into Nanny 911. Feel infantilized and ashamed as people offer up criticism and advice.
• Attend those parenting classes and learn wise things such as "discipline is derived from the word disciple," but know that a simple parental "no" triggers an atomic rage where the child can become almost feral. All the consistency and star charts in the world don't work with such an unstable child.

A mother from Colorado told us:

I kept thinking there must be something wrong with us. Nothing made sense. I read all the books. I listened to my girlfriends with infants. I couldn't believe our daughter was so different. She was so smart and precocious. She read at age two, and raged with the word "NO" at about the same time. Our toddler had an explanation of why she should be able to do what she wanted to do and now!!! And it didn't matter if it were 2 or 4 in the morning.

Many parents, like the mother above, will attempt to understand these temperaments and behaviors by telling themselves: "She's extremely bright"; "He's so sensitive and artistic"; "These traits are going to make him a very successful adult someday, if only we can survive his childhood"; "It's just a phase--he'll grow out of it."

Sooner or later, though, if the symptoms become more severe and disruptive, the parents are going to look for professional advice (or they are going to be directed toward professional advice by the pre-school teacher or the school psychologist).

The decision to get a consultation with a child psychiatrist is typically the visit of last resort, and comes only after years of trying to assert authority in a household, and watching a child spin out of control and be unable to function as children should.

Once the parents accept that they need help, they come face-to-face with serious roadblocks as they come to find that there are only 4100 or so child psychiatrists in this country (just two in Wyoming; 20 in Mississippi; and 31 in Iowa, to name a few).

It's not atypical for parents to struggle for months to find a doctor who believes in the illness and knows how to treat it, but then there are often waiting lists of eight months. We know families who travel through five states to make an office visit.

If the child is incorrectly diagnosed with ADHD, OCD, ODD, PDD, anxiety disorder, or simple depression, he or she might be placed on a stimulant or an antidepressant which could worsen the behaviors significantly.

Once parents do agree to a trial with mood stabilizers or atypical antipsychotics, they read the package inserts of these drugs with alarm as they read serious black box warnings and side effects that would make anyone waffle about the decision. They then watch apprehensively for any signs of serious trouble such as lithium toxicity, tardive dyskinesia, Stevens-Johnson syndrome, new-onset type-II diabetes, or pancreatitis. Side effects such as weight gain are extremely disturbing to the child as well as to the parents, and these feelings should not be underestimated.

As parents become all too familiar faces at the pharmacy, not only do they experience shock at the cost of each prescription (despite co-pays), but fear that someone in their town will overhear the pharmacist talk through the medications, thus revealing their children's diagnoses to anyone nearby.

If anyone knows some parents who would sign up for all of this just to "get themselves off the hook" and not be responsible for their "bad parenting," we'd like to meet them. In most cases, medications are the choice of last resort.

Two mothers wrote and seemed to sum up the experiences of the many of hundreds of parents with whom we've spoken to, or corresponded with, since the publication of our book, and they are both worth quoting at length.In response to our inquiry about her feelings about medications, one mother emailed:

How do we feel about his meds? Well I can definitely say that Zachary hates them, with a passion. The atypical antipsychotic has made him gain weight and he hates the stigma of being on the meds. But at the same time he understands fully that the meds are the only thing keeping him stable and out of the hospital.

They have become the necessary evil. The road to finding him meds with lower side effects and the ability to keep him stable has been long and hard. I am filled with such heartbreak and guilt to be putting this child through this but I understand that this is what enables him to function in a day. We did not choose this course lightly. Without the meds he would be in a constant state of mania or depression and the terror of his being in those states to him and us is excruciating.

The last few months of having him stable and being able to see our real boy--his personality, his humor, his love and excitement of the world--is a gift.

The second mother detailed the journey she and her husband had traveled to the pharmacy. She said:

By the time Adam was five years old, we had already been through three years of out-of-body tantrums, wildly erratic behavior, and sleepless nights. The doctor said our son's case was very complicated and handed us a list of recommended child psychiatrists with his best wishes.

We resisted medication against medical advice, because our son was so young and so unformed. How could we give such serious medicine to such a little boy? We thought maybe if we just stuck it out, he would outgrow it. We undertook psychotherapy, with all the accompanying behavior modification strategies, implemented both at home and at school but little of it seemed to make a difference for long, if at all.

Eventually this couple did decide to initiate the trial of drugs their doctor prescribed, but none of them were very successful either. At one point the child was on an antidepressant and he kept screaming that there were snakes crawling all over his bed and slithering down to the floor of his room. (He was weaned as quickly as was safe from the drug.)

She continued:

Finally, at age 12, a different doctor told us that the medication he was on could be making his symptoms worse, and prescribed a mood stabilizer.

This was the turning point in the life of our son. On the new medication, he came into his own. The extreme mood swings, the anger, irritability and out of control behavior went away. For the first time we saw his true nature and his abilities, instead of just his DISabilities. He had friends for the first time. Lots of them. He went from being known as "the troublemaker" to being known as the kind, compassionate one, the boy who was eager to please, the boy who despite his struggles with academics, tried his best and made progress in each subsequent grade.

Unfortunately the worry about medications doesn't end by looking at a well-functioning child. The irony of this illness is that the better the child does, the more tortured the mothers and fathers are for having made the decision to administer medications in the first place.Adam's mother commented about this second-guessing that parents do:

Now our son is 18. He'd been so good for so long we could hardly remember those dark, dark days. We began to wonder what would happen if we gave him less medicine. After all, he had been growing and maturing and maybe he'd experienced a neurological growth that would make him less dependent on drugs. He was so good that I started to question my judgment--why haven't we tried to wean him off some of this stuff? Have I been medicating my son unnecessarily all these years? Soon that question was answered.

Our son went to a pre-college program this summer and was supposed to be personally responsible for taking his medications. On the phone he was in a happy mood, spoke enthusiastically about his experience, and received glowing reports from the staff. Then, suddenly, out of the blue, he started to report feeling unhappy. He wasn't getting along with friends, he was unable to sleep or wake up on time.

We thought he was just homesick, but then his supervisor called and said something was terribly wrong. He was a different person. It was as if he had fallen off a cliff. We brought him home and took him to the doctor. He had a blood test to check his medication level. Sure enough, it was way below the therapeutic range. Further investigation revealed that he had failed to take his medicine on a regular basis.

That night, at home, he had an emotional breakdown unlike any we'd seen since the dark days. Our younger son woke us frightened in the middle of the night and said: "Quick, come fast, there's something very wrong with Adam." We ran in and saw him, lying face down almost off the bed, sobbing uncontrollably and moaning that he didn't know what was going to happen to him. I will never forget the shock of looking down on the floor and seeing tears pooling on the floor (that is an image I will carry all of my days).

It has been three weeks since that incident and he is once again at therapeutic levels. He is back to normal, happily engaged in his usual social life, helping the director of his school get the rooms ready for the opening of classes in a few days.

It was a terrible, emotionally-expensive way to learn a lesson. But now we know for sure. Our son needs medication to have a life. So next time someone insinuates "How COULD you?" and there will always be those who do, I can answer to myself, or right out loud, "How could I NOT?"

Quite a journey. A parent is forced to help their child, but they can never rest easily or know whether the course they've taken is the right one. And for everything that can be gained with proper medications, it comes at a high price for the children and the parents who worry about long-term side effects, weight gain, stigma, criticism, and the often difficult-to-dislodge lowering of the child's self-esteem.

Doctors and parents need support, not irreverent sketches and wholesale suspicion. This illness needs tremendous research, not reveries about whether or not it exists in childhood.

Toward the end of To Kill a Mocking Bird, six-year-old Jean Louise (Scout) is sitting with the Reverend Sykes in the gallery of the courtroom when her lawyer father, Atticus Finch, walks toward the exit. Reverend Sykes, so profoundly moved by what Atticus has tried to do for his people, in that time and place, tries to get Scout's attention. He calls to her: "Jean Louise? Jean Louise. Stand up. Your father's passing."

We paraphrase those words, and with equally deep respect when we say: "Stand up. The parents of a child with bipolar disorder are passing." And their journey has been more difficult than the media and the outside world will ever know.

We send you our best,

Janice Papolos and Demitri Papolos, M.D.

Bibliography:

ABC Radio National's "Background Briefing With Jane Shields"

Lee, Harper. To Kill a Mocking Bird. New York: Harper & Row, 1961.

Papolos, J and D. "In Honor of Mothers and Fathers." The Bipolar Child Newsletter, May, 2006, Vol. 24.

Papolos, J and D. "Why Is It So Difficult to Diagnose This Disorder?" The Bipolar Child Newsletter, May, 2007, Vol. 23.

Papolos, Demitri, and Janice Papolos. The Bipolar Child. Third Edition. New York: Broadway Books, 2006. Additional News:

The new DVD and 2 CD-set of "24: A Day in the Life of Bipolar Children and Their Families" has gone back "to press" a second time since June.

This DVD validates a parent's experience as well as explains why these children rage with the mother (but rarely in the outside world), why they can't get up in the morning, why they are so disorganized and have such trouble in school, plus all their difficulties--day and night. There is a wealth of ideas to ease their way.

Purchase orders from school systems are coming in from all over the country and a mother in New Jersey just emailed:

"Janice, you should know that so many teachers, counselors, and tutors in Ryan's school have watched your video, and it's been an incredible aid. His group of teachers now have some insight that makes their relationship with him so much more productive.

In our book, and in almost every newsletter we write, we talk constantly about the burdens that parents of children with bipolar disorder must shoulder and overcome, all the while attempting to make decisions with the clinicians who work in an area of medicine that is still in its infancy.

But we've never composed a stand-alone list that lets others look at what the parents must grapple with and withstand--in all its stark and disturbing reality.

This list, sadly, cannot even be described as "exhaustive or complete," but as Mother's Day approaches, and Father's Day is just a calendar turn away, the parents coping with a child (or children) with bipolar disorder deserve special recognition and honor for their enormous valor as they:

• Look at a very young and much-loved child with a nagging fear that something is seriously wrong.
• Feel the external world bearing down on them, advising them to take multiple parenting classes or to tune into Nanny 911. Feel infantilized and ashamed as people offer up criticism and advice.
• Accept that they need help from a professional, but feel a stranglehold of fear.
• Come to learn that there are only 4,101 child psychiatrists in the entire United States--many wary of making this diagnosis.
• Watch their child and other siblings besieged by an illness for which there is little diagnostic or treatment consensus in the field of psychiatry.
• Receive multiple diagnoses such as ADHD, OCD, ODD, PDD, anxiety disorder, or simple depression.
• Come to accept that the child has a very serious psychiatric illness and make the agonizing decision to begin a trial of medications (if they can find a psychiatrist who can treat their child, or who has open hours).
• Read the package inserts of medications which list possible side effects, as well as frightening black-box labels, and watch apprehensively for any signs of serious trouble such as lithium toxicity, tardive dyskinesia, Stevens-Johnson syndrome, new-onset type-II diabetes, or pancreatitis.
• Attempt to explain to a child how the doctor is trying to help and what the medications are going to do; subsequently they watch their child experience distressing early side effects that include nausea and diarrhea and severe drowsiness; or worse, the paradoxical effects that produce the opposite reaction of what the drug is being used to treat.
• Deal with the disillusionment of a failed medication trial and explain to that child why those pills didn't work and tell him or her: "We're going to try something else," knowing that they may have to repeat that phrase a number of times and thus begin a new round of side effects.
• Have to get a child who has a needle phobia to a lab for a blood draw to determine drug levels. (This experience alone could turn one's hair grey.)
• Watch children's weight balloon upward and their self-esteem plummet as they take certain medications that can be very effective, but that may also cause weight gain.
• Become an all too familiar face at the pharmacy, experiencing shock at the cost of each prescription.
• Have to suffer the ignorance of people in the media, who--in a cavalier manner--discuss over-diagnosis and over-medication. Moreover, these parents hear certain clinicians in the field publicly utter insulting sound bites such as: "This is an easy way for parents to let themselves off the hook;" or "This is simply the diagnosis du jour."
• Have to listen to the word "No!" from a child one hundred times each morning, but be unable to assert the parental "No" as it will predictably trigger a meltdown.
• Suffer the physical abuse of a child raging out of control, and experience crippling shame because they can't manage their own child.
• Are set adrift in a house that has become a war zone.
• Deal with feelings that alternate from extreme anger at the child to the most unbelievable yearning to help that child, from anger at the outside world for failing to realize what is happening to them, to exhaustion in trying to deal with the child with some modicum of equanimity.
• Become perplexed that their child often does well in the outside world, only to return to the safe harbor of home to rage at a parent (most often the mother), leading to the suspicions of outsiders that "Something must be going on in that household, and with that woman;" or "She seems so nice, but you never really know people;" or "He can keep it together at school, so he must be a very manipulative kid.
• Have to mount a siege each school-day morning simply to get a child suffering a sleep/wake reversal up and out to school.
• Hesitate to answer a phone, afraid that it will be the vice-principal in charge of disciplinary action calling to report an "incident" at school.
• Come close to earning a degree in educational law so as to work with the school system. Keep in constant contact with the teachers and psychologist or aide in order to assess what's working and where yet another accommodation may help.
• Waylay careers and reduce household income so a parent can stay at home to deal with the child and spend hours at doctors' and therapists' and tutors' offices.
• Experience the heartbreak of knowing that their child is rarely invited to birthday parties. Conversely, if he or she is invited, the event might be overstimulating thus provoking some kind of meltdown, and effectively putting an end to any such celebrations in the future.
• Fear that their child will become aggressive with kids on the playground or in the neighborhood, thus earning disdain and a cold shoulder from the other parents.
• Want the world to understand, but fear that the stigma will further isolate the child and their family.
• Attempt to explain the almost inexplicable to the siblings, and to help them cope with the chaos in the household. Feel overwhelming guilt that the family is always fractured as one parent goes to a soccer game while the other stays home with the unstable child; or that a rare dinner at a restaurant devolves into an embarrassing, abruptly-ended event as parents race the child and siblings home and away from disapproving diners.
• Are paralyzed if a child becomes manic and hypersexual and says inappropriate things or makes inappropriate gestures.
• See their marriages become shaky as the stress of coping with this illness leaves parents little time to relate to each other and most conversations begin to center around the problems of their ill child.
• Listen with horror as their child screams, "I don't want to live anymore;" or "I'd be better off dead."

____________________________________________________

It is hard to fathom how these parents get through a day. Their reality is simply unimaginable to the outside world, and their lives--until their children are stable--are a virtual stew of guilt and powerlessness, anxiety, fear, uncertainty, confusion, blame, and shame. These are feelings that most of us would do anything to avoid, but all are feelings that a family who lives with bipolar disorder must endure for months and years at a time.

And yet, we see family after family find the help, learn to cope, steady their footing, and move on with their lives. And then we see them turn around and offer a lifeline of information and support to others who must walk the same path, only now no longer alone.

Some people think of Mother's and Father's Day as Hallmark holidays; but we see them as an opportunity to celebrate these parents: their grit and their commitment, their love and their humanity....Parents who have never stopped trying to help their children--against seemingly overwhelming odds.

Take good care of yourselves.

We send you our best,

Janice Papolos and Demitri Papolos, M.D.

The Child Bipolar Questionnaire is available free-of-charge in English, Spanish, Portuguese, Polish, and French at the Web site of the Juvenile Bipolar Research Foundation

In response to many requests from parents and clinicians, the JBRF developed programming for the automatic scoring of the Child Bipolar Questionnaire. The result is a printed score-sheet listing important scores and their diagnostic indications, as well as dimensions of impairment indicated by item responses. Parents and clinicians may purchase this service by using PayPal.

On October 22, The New York Times ran a front-page article about a 10-year-old girl named Haley, suffering with a probable bipolar disorder. Because Haley was extremely anxious and distractible, had obsessional thoughts and fears, exhibited rapid mood swings, was often aggressive, and was experiencing psychotic symptoms, her psychiatrist could not point to one, specific diagnosis. "Her screening," he said, "showed that she met criteria for every mental disorder listed."

He went on to tell journalist Pam Belluck, that "Her symptoms suggested anxiety, morbid thoughts, obsessions of a possibly sexual nature, frequent fluctuations in mood, periods of euphoria, giddiness, irritability, rapid speech, auditory and visual hallucinations, thought disorganization, vocal tics, distractibility, poor socialization in school, sensory integration issues, attention impulse disorder, manic behavior, sleep disturbance."

After the article appeared, people called and emailed us and expressed their confusion about Haley's diagnosis. Did she have a mood disorder plus obsessive-compulsive disorder, attention-deficit disorder with hyperactivity, anxiety disorder, sensory integration disorder, a sleep disorder, and a psychotic disorder? Could this ten-year-old actually have six or seven disorders that were co-occurring at the same time?; Why was the diagnosis of bipolar disorder so tentative? They pointed to her rapid mood swings, hypersexuality, periods of elation and giddiness, grandiosity, and sleep disturbances--all hallmarks of a bipolar disorder. Many seemed extremely frustrated with the lack of knowledge about Haley's condition.

So we thought that perhaps the time had come to write a newsletter focusing on the diagnostic conundrums and controversies of the psychiatric conditions in childhood, with a specific emphasis on the diagnosis of pediatric bipolar disorder.

Diagnosing Non-Psychiatric Illnesses

Anyone who has seen the medical-mystery show, House, knows that there is an opening scene in which a man, woman, or child collapses from some mystifying illness. Just after the titles and the first commercial, viewers get to see the brilliant and misanthropic, Dr. Gregory House, assemble his team of specialists (whom he proceeds to abuse). House scrawls the patient's symptoms on an easel and asks his young hotshots to suggest candidate diagnoses that would account for all the symptoms. (The short list of candidates is called the differential diagnosis.)

House scrawls their suggestions on the easel as well, and then abruptly orders MRIs, other scans, sophisticated lab work to test for what he considers the most likely diagnosis. Never right the first time, however, House and his team go back to the drawing board, cross out the initially-proposed illness, and home in on another (more abuse). At show's end, we see the patient walk out--cured--from a difficult to discern, but ultimately named, single, medical condition.

Not So in Psychiatry

The human brain is the most complex structure on earth. Packed into three-and-a-half pounds of grey and white matter, compressed into a structure no larger than a grapefruit are perhaps 100 billion brain cells, each linked to as many as 10,000 others. It is said that the number of possible interconnections between the cells is greater than the number of stars in the universe.

The brain is very plastic by design--it develops and changes and is impacted by environment. In addition, each person experiencing a psychiatric illness expresses it through the unique filter of mind and temperament.

Diagnosis in psychiatry is a problem. After all, there are no lab tests in psychiatry that conclusively pinpoint a diagnosis, and there are a host of overlapping symptoms (especially in children's disorders).
The psychiatrist's main diagnostic instruments are the patient's report of symptoms (tough to get in young children), observable behavior, the parents' report, family history, and the clinical course of the disorder.

Distinguishing between normal behaviors and pathological ones in a young child is even more challenging for a number of reasons: The span of time in a young life is insufficient to establish a course of illness; developmental factors are in full play; and a child's often nonstop motion, lack of impulse control, difficulty tolerating frustration, and vivid imagination are part of a typical, everyday picture.

So How Does a Psychiatrist Make a Diagnosis?

The most recent criteria established by the American Psychiatric Association (APA) are delineated in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders. With some interim changes, it is officially called the DSM-IV-TR, Text-revision), but for our purposes we will refer to it simply as the DSM-IV.

Today, the DSM-IV holds great sway over psychiatrists and their ability to diagnose and select treatment modalities. Should a doctor seek reimbursement for a clinical evaluation or an office visit, a DSM-IV diagnosis must appear on the patient's insurance form.

Yet it bears knowing that the DSM is based on a paucity of scientific research, has never been validated, and is the product of 25 committees and multiple voices. Its final conclusions and criteria were sometimes pushed by the winds of politics and personalities. Shouting matches were not uncommon as the manual took shape.

Moreover, the decision was made to diagnose according to a categorical system, a sort of Chinese menu of symptoms and observed behaviors. For instance, the diagnostic criteria for attention-deficit disorder with hyperactivity (ADHD) requires six out of nine symptoms describing inattention; as well as six out of nine describing hyperactivity-impulsivity.

In addition, the categorical design of the Diagnostic and Statistical Manual sequesters individual symptoms into arbitrarily-divided disease categories that, in effect, dismisses the concept of overlapping symptoms. Each cluster of symptoms is walled off in its own airtight box.

So, unlike the other specialties in medicine, a psychiatric patient may receive multiple diagnoses. For instance, if a child with bipolar disorder also meets criteria for ADHD (and a majority of them do), then he or she is diagnosed as having both bipolar disorder and ADHD. If the child is experiencing manic symptoms, is fidgety and distractible, appears oppositional, is extremely anxious about being separated from his or her mother and has panic attacks as well as germ phobias, the child is plastered with an alphabet soup of diagnoses: bipolar, ADHD, Oppositional-Defiant Disorder (ODD), and multiple anxiety disorders (obsessive-compulsive disorder is considered an anxiety disorder).

What Does the DSM-IV Say About Children and Mood Disorders?

Children are mentioned in the DSM-IV, but they are to be diagnosed according to adult criteria. And this is where huge problems develop. Clinical investigators are beginning to realize that bipolar disorder in childhood presents in a very different pattern--one that bears little resemblance to classical cycles of mania and depression as they are expressed in adulthood. For instance, children have more irritable moods with explosive outbursts, and their cycles of mania, hypomania, and depression are far more rapid than the typical adult presentation. Yet the DSM-IV specifies that a mood episode must last for a specified period of time.

For instance, duration criteria for the diagnosis of a hypomanic episode requires a "period of persistently elevated, expansive, or irritable mood lasting throughout at least four days." (Italics ours.) Yet a significant proportion of early-onset bipolar children have a form of the condition that is marked by frequent mood and energy shifts that occur multiple times throughout the day.

For a depressive episode, the DSM-IV duration criteria is even more demanding: The manual requires at least a two-week period with five or more depressive symptoms. Therefore, by definition, an individual who has rapidly shifting mood states of less than the required duration cannot be formally diagnosed as having bipolar disorder.

A separate and distinct category--Bipolar Disorder Not Otherwise Specified (NOS)--was established to include disorders with bipolar features that do not meet full duration criteria. While most children with bipolar disorder fit into this category, still it is not an accurate description of the condition as it presents in childhood.

So, Haley's doctor and other clinicians and researchers are in an extremely difficult position: When they attempt to diagnose children with bipolar disorder, either they cannot use DSM-IV criteria and must describe these children as having "mania-like symptoms," or they must modify other diagnostic instruments in order to treat the primary problem. Alternatively, they can diagnose BP-NOS.

How Does Bipolar Disorder Actually Present in Childhood?

Children with bipolar disorder veer from irritable, easily annoyed, angry mood states to silly, goofy, giddy elation, and then just as easily descend into low energy periods of intense boredom, depression and social withdrawal, fraught with self-recriminations and suicidal thoughts. These abrupt swings of mood and energy can occur multiple times within a day, and intense outbursts of temper (rages that can go on for hours), poor frustration tolerance, and oppositional defiant behaviors are commonplace. The children frequently suffer severe anxiety--separation anxiety, generalized anxiety, and panic disorders--as well as obsessive-compulsive symptoms, particularly aggressive obsessions, hoarding, the need for symmetry and ritual requests for reassurance.

Moreover, many of the children have sleep disturbances, often accompanied by night terrors, nightmares filled with blood and gore and themes of pursuit and abandonment, as well as other arousal disorders of sleep.

Accompanying elevated periods of mood may be an increased sexuality (hypersexuality). It is an accepted fact that hypersexuality is a symptom of hypomania or mania in an adult who has bipolar disorder. In young 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.

Psychotic symptoms, such as delusions (fixed irrational beliefs), and hallucinations (hearing voices, seeing things that others don't see) are not uncommon. Sometimes the voices and visions are compelling; often they are threatening, critical, or instruct the child to act on aggressive impulses towards others or self.

The Problematic DSM-IV

When we take into account a diagnostic system that demands that moods of depression and mania last for two weeks or four days, respectively, and combine that with the historical bias against diagnosing bipolar disorder before puberty, we don't need to search very much further for reasons why this condition is so poorly recognized, and why a psychiatrist may be on shaky ground trying to conform to the diagnostic dictates of the DSM-IV.

Moreover, the strict division of symptoms into arbitrary diagnoses in a categorical system is a particular problem in early-onset bipolar disorder as so many symptoms manifest concurrently.

Some would say that these basic and arbitrary principles around which the field has organized diagnostic categories are flawed and need to be rethought and overhauled.

Dr. C. Robert Cloninger of Washington University School of Medicine makes no bones about this view when he says that "There is no empirical evidence for natural boundaries between major syndromes. No one has ever found a set of symptoms, signs or tests that separate psychiatric disorders fully into non-overlapping categories."

In simpler terms, Dr. Cloninger is making the case that there is no scientific evidence to support placing diagnostic categories into separate, airtight boxes. There is no good reason to construct artificial walls between diagnostic categories.

What Are the Questions Researchers Are Attempting to Resolve?

Three come to mind:

1. Does bipolar disorder occur simultaneously with other psychiatric disorders making it possible for a child actually to have three, four, or more diagnoses?
2. Are these clusters of symptoms that suggest distinct disorders merely early precursors on a developmental continuum that eventually expresses itself as full-blown bipolar?
3. Is there a set of symptoms shared from DSM-IV categories that more fully describe the full syndrome, and that are actually part of a spectrum of conditions that share a common biological substrate?

The truth is no one knows for certain. And until research can provide clarification, parents are going to have to tolerate a great deal of diagnostic ambiguity. Yet a correct diagnosis is vital to a child's well-being, for it is the proper diagnosis that guides the treatment and--equally important--prevents the child from being placed on medications such as antidepressants or stimulants that may considerably worsen the course of a bipolar disorder.

A Closer Look at Problematic Boundary Issues: ADHD and Bipolar Disorder

At least seven of the DSM-IV criteria used to diagnose ADHD are commonly shared with bipolar disorder as it presents in childhood. A study of 1200 cases diagnosed with pediatric bipolar disorder performed by researchers of the Juvenile Bipolar Research Foundation found exceedingly high rates of endorsement of these "ADHD" symptoms:

• Easily distracted by extraneous stimuli 96%
• Difficulty sustaining attention in tasks or play 96%
• Restlessness as if driven by a motor 71%
• Often talks excessively 80%
• Difficulty waiting turn 96%
• Blurts thoughts out 96%
• Often has difficulty organizing tasks 91%

Many of the most commonly used diagnostic inventories employed by mental health professionals to diagnose ADHD include symptoms that would be indistinguishable from the most common symptomatic profiles observed in children with bipolar disorder. Therefore, since attentional problems, motor disinhibition, and organizational deficits are part and parcel of both conditions, it is difficult to make a clear diagnosis. If a clinician diagnoses according to strict DSM-IV criteria, and there are symptoms of mania present also, than, as we mentioned earlier, both bipolar disorder and ADHD must be diagnosed as co-occurring disorders.

What Is Another Way To Classify Psychiatric Diagnoses?

A considerable amount of recent research has focused specifically on whether psychiatric disorders are best classified dimensionally. Some clinical investigators believe that a dimensional approach (which calls upon new statistical methods to examine patterns of symptom co-occurrence) could help take into account biological relationships as well as a common underlying genetic predispositions yet to be discovered among research subjects.

Co-occurring diagnoses might best be explained by the presence of common, shared symptoms that are linked and exist along a continuum.

What Are The Advantages of a Dimensional Diagnostic System?

Data derived from these models of patterns of co-occurrence among bipolar spectrum conditions in childhood (e.g. ADHD, OCD, separation anxiety disorder, oppositional defiant disorder, and others) may help determine whether they are, in fact, indicators of a coherent underlying domain, rather than separate conditions with little or no relationship.

The promise of a dimensional model of classification is that it could provide a more specific and individualized profile description of a patient's illness that may in turn offer better treatment strategies.

Has a Dimensional Approach Been Studied?

Research studies that use a dimensional approach to diagnostic classification and that have the potential to clarify the current diagnostic confusion in juvenile-onset bipolar disorder are already underway. Early reports suggest that the condition may indeed be better described along a continuum with specific features of other disorders, in addition to features included in the present DSM-IV criteria for mania and depression.

A unique screening inventory called the Child Bipolar Questionnaire is used frequently by the Juvenile Bipolar Research Foundation and has revealed some interesting findings.

The Child Bipolar Questionnaire

Until very recently, newly-proposed diagnostic criteria for juvenile-onset bipolar disorder have been based on information from very small clinical samples, or from expert consensus. Diagnostic rating scales used in clinical studies have all been modified from adult versions that are derived from DSM-IV diagnostic concepts, and focus almost exclusively on symptoms of mania and/or depression.

This focus limits the capacity to encompass a broader view afforded by a dimensional analysis of the primary features of the illness.

In order to avoid imposing such artificial distinctions that carve out symptoms into pre-established diagnostic categories, and to address the fact that psychiatric rating scale instruments do not represent a finer grained dimensional view of the condition, the Child Bipolar Parent Questionnaire (CBQ) was developed.

This is a 65-item questionnaire completed by a parent or parent surrogate that is based upon a Likert Scale. The questionnaire requires a rating for frequency of occurrence for each of the 65 symptoms or behaviors. For instance, a rating of 1 signifies that a symptom or behavior never occurs, or occurs only rarely; a rating of 4 signifies that a symptom or behavior occurs very frequently, or almost constantly. It was developed to serve as a rapid screening inventory of common behavioral symptoms and temperamental features associated with pediatric bipolar disorder. (To read about the development of the CBQ, or to complete the screening inventory, visit http://www.jbrf.org/cbq/index.html).

The ability of CBQ screening diagnoses and of the CBQ Core Index subscale to effectively predict diagnostic classification by structured interview was assessed using the well-validated Kiddie-SADS P/L. The validation study of the CBQ is published in the Journal of Affective Disorders (see bibliography below).

What Did a Dimensional Analysis of the CBQ Reveal in a Large Sample of Children Diagnosed With, or at Risk For, Bipolar Disorder?

In a sample of over 2,000 children, researchers originally identified 11 factors that represent dimensions of impairment associated with juvenile-onset bipolar disorder. These factors are best described as:

• Poor frustration tolerance
• Dysregulation of attention/executive function deficit
• Depression/poor self esteem regulation
• Low threshold for arousal/sensory sensitivity
• Poor regulation of aggressive impulses
• Sleep/wake cycle disturbances
• Anergia/depression
• Poor regulation of sexual impulses
• Grandiosity/mania
• Fear of harm (to self or others)
• Low threshold for anxiety.

On subsequent analysis of these eleven factors in a sample of sibling pairs both affected with the illness, four of these factors were found to have the highest concordance rates: anxiety, attention deficit, fear of harm, and aggressive behavior, in addition to the traditional categorical symptoms of mania embedded in the DSM-IV.

So, rather than characterizing the condition as a potpourri of different diagnostic entities, these findings support the existence of a distinct behavioral phenotype that includes primary symptoms from overlapping DSM-IV categories such as anxiety disorders and disruptive behavior disorders, as well as primary symptoms of juvenile mania.

Back to Haley

So if we go back now and look at many of the symptoms that Haley exhibited as described in The New York Times article: manic behavior, frequent fluctuations in mood, periods of euphoria, giddiness, irritability, rapid speech, hypersexuality, auditiory and visual hallucinations, anxiety, morbid thoughts, sleep disturbance, distractibility, poor impulse control, and aggressive behavior, we can see that the predominant symptoms that Haley displays are in the realm of bipolar disorder.

Adhering to DSM-IV criteria, however, may confuse the clinical picture by imposing arbitrary duration criteria on mood swings that are almost always rapid and abrupt, and dividing the panoply of symptoms into a handful of categorical diagnoses.

By incorporating a dimensional view as we've suggested above, many of the observed symptoms would round out a complete picture of bipolar disorder as it more typically presents in childhood.

In Conclusion

Allen Frances, the chairperson of the task force that produced DSM-IV wrote that "We are at the epicycle stage of psychiatry where astronomy was before Copernicus, and biology before Darwin. Our inelegant and complex current descriptive system will undoubtedly be replaced by simpler, more elegant models."

From many vantage points, we appear to be approaching a paradigm shift in psychiatric diagnosis, and, as we all well know, these tectonic shifts don't occur without great upheaval. Childhood-onset bipolar disorder may very well be at the epicenter of such a shift in psychiatry.

For the sake of the children and the families and the doctors who are forced to grapple with the diagnostic dilemmas, may the shift come soon and with greater validity.

We'll write again soon, but before we sign off, we'd like to tell you how pleased we are that the third edition of The Bipolar Child has recently been published by Broadway Books. This new edition is significantly expanded and revised with over 22,000 words added to the text.

It is our hope The Bipolar Child, Third Edition will be extremely helpful to you and your children, and to their educators and treatment teams.

As always, we look forward to hearing from you. May the holidays usher in a new year of hope and peace.

We send you our best,

Janice Papolos and Demitri Papolos, M.D.

Bibliography

American Psychiatric Association. Diagnostic and statistical manual of mental disorders (3rd Edition) Washington, D.C.: 1980.

American Psychiatric Association. Diagnostic and statistical manual of mental disorders (4th Edition, text revision) Washington, D.C: 2000.

Belluck, P. "Living with love, chaos and Haley. " The New York Times, October 22, 2006. (http://nytimes.com/ref/health/troubled-children.html)

Krueger, RF., Barlow, DH, Barlow, Watson, D. "Toward a dimensionally based taxonomy of psychopathology." Journal of Abnormal Psychology. 2005; 114, 491-493.

Kupfer, DJ. "Dimensional models for research and diagnosis: A current dilemma." Journal of Abnormal Psychology. 2205; 114, 557-559.

McManamy, J. Living Well With Depression and Bipolar Disorder. New York: Collins, 2006.

Papolos D, Hennen J, Cockerham MS, Thode HC Jr, Youngstrom EA. "The Child Bipolar Questionnaire: a dimensional approach to screening for pediatric bipolar disorder." Journal of Affective Disorders. 2006; 95,149-158.

Papolos D, Hennen J, Cockerham MS, Lachman H. "A strategy for identifying phenotypic subtypes: Concordance of symptom dimensions between sibling pairs who met screening criteria for a genetic linkage study of childhood-onset bipolar disorder using the Child Bipolar Questionnaire." Journal of Affective Disorders. 2006; [In press. Epub in advance of print publication]

Papolos D, Hennen J, Cockerham M. "Obsessive fears about harm to self or others and overt aggressive behaviors in youth diagnosed with juvenile-onset bipolar disorder." Journal of Affective Disorders. 2005 89, 99-105.

Papolos, DF. "Bipolar disorder and comorbid disorders: The case for a dimensional nosology." In Bipolar Disorder in Childhood and Early Adolescence, ed. Barbara Geller and Melissa P. Delbello. New York: Guilford Press, 2003.

Papolos, DF and J. The Bipolar Child, Third Ed. New York: Broadway Books, 2006.

Papolos, DF and J. Overcoming Depression, Third Ed. New York: HarperCollins, 1997.

Puig-Antic, J., Kauffman, J., et al. Schedule for Affective Disorders and Schizophrenia for School-age Children (Kiddie-SADS). Pittsburgh: Western Psychiatric Institute and Clinic, 1986.

Spiegel, A. "The Dictionary of Disorder." The New Yorker Magazine. January 3, 2005.

Widiger, TA, and Samuel, DB. "Diagnostic categories or dimensions? A question for the Diagnostic and Statistical Manual of Mental Disorders--Fifth Edition." Journal of Abnormal Psychology. 2005; 494-504.

Each week, millions of viewers tune into the hit show, 24. They watch as federal agent Jack Bauer of the Counter Terrorist Unit battles threats to national security, barely escaping with his life. The season unfolds in real time: each show depicts one hour; each season, 24. Every so often, a split-screen panel updates the audience about the parallel adventures of other key characters in the story, and, before commercial breaks, the tension is heightened as a digital clock ticks away the hour, the minutes, and the seconds. It's a pretty electrifying hour of "must-see-TV."

24 hours in the life of many children with bipolar disorder and their families is just as heart pounding: filled with threats, crises, and cliffhangers. But the hours are interminable (no one yells "Cut!"), there are no commercial breaks, and there is never a hiatus when the set shuts down and the cast and crew fly off to exotic locales.

No, this is real time 24/7. And because this intense struggle is so difficult for others to understand, we thought we would condense some of what many children and parents are experiencing, with the hope that one document reveals a day in the life.

6:30

The Day Begins:

Parents typically wake to an alarm and immediately face the day with churning stomachs and dread. Probably due to a phase-delay in the pattern of their children's sleep, their sons and daughters typically have difficulty going to sleep at night, and they cannot be awakened in the morning. Parents have to mount a siege simply to get their children up and out the door. One mother described it like this:

Yesterday morning it took an hour-and-a-half attempting to get him up. We kept shaking him, beseeching, threatening, beseeching anxiously.... We even called his cell phone thinking he might pick it up for a friend's call. He simply growled, muttered something we would have preferred not to hear, and turned over and went back to sleep.

We finally did see him rise from the bed and we ran the shower thinking that might wake him up. Ten minutes later we found him in the bathroom curled up on the bath mat, sound asleep.

While it may seem as if the child or adolescent is behaving in an oppositional manner, a great many of these youngsters actually suffer from something called sleep inertia.

What Is Sleep Inertia?

Sleep inertia is a transitional state of lowered arousal occurring immediately after awakening from sleep and producing a temporary decrement in any subsequent performance. Studies show that sleep inertia can last from a few minutes to four hours. Youngsters with bipolar disorder are far closer to the latter than the former. One 17-year-old girl described her attempts to get up in the morning this way:

I feel as though my insides are whining. I will do anything not to get up. Sleep is more important than anything in the world. I could sleep until 4:00 in the afternoon. I never think about it from my mother's point-of-view. I don't think anything. When I do get to school (after much yelling by my mother and me back at her), I have my head on the desk until somewhere around 11:00 in the morning. Right before lunch I seem to truly get up.

The "phase delay" of their 24-hour rhythms often makes these youngsters sluggish in the morning; more activated as afternoon gives way to evening; and then the rocket thrusters go off as bedtime approaches. Their energy level can climb so high, their thoughts often race, and they are unable to shut down and get to sleep. The next morning this same pattern begins again.

Several other facts make it difficult for a child to get up. The medications can be sedating; he or she may be depressed and chronically tired; or the thought of facing the school day may produce waves of anxiety or panic and the child may express somatic complaints (stomach aches and headaches). Parents are always forced to make a decision: Are the complaints an emerging "bug," or is the child feeling excessive anxiety and trying to stay home where he or she feels more comfortable.

And this all happens before the orange juice appears on the table.

The bus ride to school can also be fraught with anxiety for the child, as he or she may feel singled out for teasing or bullying, and the noise level can be extremely irritating. Parents often have to drive their still-soporific children to school, risking being late themselves, and sparking anxiety about their own job security.

8:00

School Begins:

While some children look forward to seeing their friends in the morning and may anticipate certain classes or activities, the student with bipolar disorder is shouldering some serious impediments to any comfort level or availability for education.

In addition to morning sluggishness and the anxiety, many kids with bipolar disorder have difficulty interpreting social cues and may feel that other kids are finding them odd or out of step.

Author Tracy Anglada, in her upcoming book Intense Minds writes that:

Few children with bipolar disorder feel that they can relate to the outside world. In many ways they have difficulty relating to themselves. They don't feel like they fit in, even with people who care for them. Especially during depression, the world seems to be passing them by, as if there were a barrier between them and everything else. Even in a room full of people they can feel totally alone.

She goes on to quote a young girl named Lee who says, "I would just stop, wherever I was, and watch the world exist, wondering how they all did it, and wondering why it all came so easily for them."

Adding to their discomfort with classmates, children and adolescents with bipolar disorder often suffer significant weight gain from the medications they take, and-to put it bluntly-fat kids are rarely on the "A List" in terms of popularity. Their self-esteem is extraordinarily low. Their level of irritability is high and can be exacerbated by the chaos and noise of students pushing through hallways. The days are fast-paced with so many transitions and these youngsters lack flexibility and do not transition easily.

And this is the first 90 minutes of the day and academics haven't even entered the picture.

(Split Screen): Meantime, the parents are at home or have reached work and are worried that every time their cell phones ring it will be the child pleading to come home (many of them suffer severe separation anxiety); or it will be the school nurse reporting that their child doesn't feel well; or (the biggest fear), it will be the Vice-Principal in charge of disciplinary issues calling to discuss "an incident" in which the child lost control, or was irritable and disrespectful to a teacher, or got into a fight with another child.

On the other hand, some parents don't have to worry during the school day, as their children seem to be able to keep things together in the outside world and save all their pent-up frustration and anger for the mother when they get home. (More about this later.)

8:00 - 2:45

The Longest Day:

If all students with bipolar disorder did well in school and achieved a sense of mastery in their work, they'd have a balancing force that would smooth out some of their anxiety and worry and frustration. But this is rarely the case. Many of these children have co-occurring learning disabilities (difficulties with reading, writing, and mathematics), and most have significant attentional problems. In addition, evidence is rapidly accruing that a majority of these children and adolescents have many deficits in the area known as "executive functions."

What Are Executive Functions?

The frontal lobes of the brain (including the prefrontal cortex, which is a layer of tissue that lies just behind the forehead) are the most forward part of the brain. The frontal lobes coordinate speech, reasoning, problem solving, strategizing, attention, self-control, organization motor sequencing, working memory, and other processes central to higher functioning. Working memory-the ability to hold information in short-term memory while manipulating it toward problem solving or sequencing it in a logical order-allows human beings to tackle and complete tasks. All of these abilities and more are essential for success in the academic environment as well as all other situations in life, particularly as the child reaches middle school and beyond.

Many youngsters with bipolar disorder are severely compromised in these abilities.
These students can be so distracted by external stimuli and it is difficult for them to sustain attention and interest in the material being covered in the classroom. Many seem to get lost in space and time, and easily become bored. (Some kids will attempt to seek stimulation by becoming the class clown or by becoming provocative.)

Time is so indeterminable and fuzzy to some of these students that they can become confused as to when each class ends. Their anxiety increases and makes them irritable and even less available for education. (Educators could help in a major way if they quietly cued the student as to how much longer the class would last and could discretely inform the student as to where his or her next class was.)

And then there are the difficulties with written expression.

The Problem With Writing

There are no statistics, but it is estimated by some psychiatrists and neuropsychologists 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 or a problem with fine motor coordination; 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-the executive function deficits we spoke of above.

In addition, some students with bipolar disorder are so perfectionistic that they erase repeatedly and become extremely frustrated as the work proceeds at a snail's pace and most remains unfinished.

Moreover, 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.

Any one of these problems will make writing a demand that will most likely be resisted-very vehemently-and with increasing frustration and anger.

12:00

Lunch:

Unstructured periods of the day such as lunchtime and recess bring a host of other problems. Cliques sequester tables and team games, and the noise levels and chaotic atmosphere are overwhelming to such sensitive children. It might be best if they have a safe place in the school-the office of the guidance counselor, or a place in the library-where they can eat lunch or just relax.

2:30

Completion of the School Day:

As the time comes to pack up homework assignments and the books and papers necessary to complete them, students with bipolar disorder often have difficulty with the organizing and sequencing process that must take place in order to ensure all these materials are present and accounted for and find their way into the backpack. And if anything goes missing, the stage is set not only for failure with that evening's assignments, but for tense times with the mothers and fathers who are expected to motivate their children and oversee the evening's assignments. (Any IEP that is drafted for a child with these organizational difficulties should plan for a teacher or an aide to help in the packing of the back pack and should teach the student how to break down the required tasks for the evening and double check the materials they will need to complete them. In addition, most children should have a duplicate set of books at home.)

Many children will need a significant reduction in the amount of homework they're expected to complete each night, or should have time scheduled into the school day when they can complete the assignments, as they are dealing with other problems as the afternoon and evening draw closer.

(Split Screen): Of course none of this takes into account the seasonal changes that occur for people with bipolar disorder. Like adults, many of the children and adolescents suffer seasonal dips or accelerations in mood: they may start the school year off well, but as the days of autumn shorten, the slow-down and lethargy of depression may catch them out, and the concentration that school demands begins to elude them. They may not care what the assignments are and lack the energy to contemplate them. Conversely, the lengthening days of early spring and the increase in intensity of the daylight may promote periods of increased energy. Thoughts may begin to race, the kids have a greater urge to move, and many ideas pour into their minds. Again, concentration becomes a problem and school may feel restrictive and a waste of time, and homework may be viewed as stupid and beneath them.

3:00

Getting Home:

Since the bus ride home can be wild and disturbing, thus making incidents with other children more likely, many parents (in most cases the mothers) pick their children up at school. And now, the child who has somehow managed to keep it together throughout a day that has brought anxiety, frustration, irritation, and a sense of failure and humiliation, is in the private orbit of the mother-away from all onlookers. This simple ride home can devolve into the hell-mobile-on-earth as the child makes unreasonable demands, insists on going here or there, wants this or that kind of food, and begins shouting, kicking the back of the parent's seat, and exploding with a litany of foul language. The parent must attempt to de-escalate the gathering storm and drive at the same time.

Many pull over and try to reason with the child; sometimes this merely inflames the situation and the mother simply puts up with the abusive language and behavior and tries to get home as quickly as possible.

Some gratify the demands of the child to keep the peace (especially if the child is not yet stable or there are siblings in the car). The fury pouring out of their children at very close range is extraordinarily unnerving.

(Split Screen): If the child is able to take the school bus home, any welcome from the parent to the child may create an opportunity to vent. A simple "How was your day, honey?" may open the flood gates and a mother stands by while her son or daughter turns from the school day's Dr. Jeckyl to the at-home Mr. Hyde. If the word "no" shows up anywhere in the mother's vocabulary, the child may begin to tantrum and rage (and these rages can go on for hours).

Tracy Anglada in Intense Minds describes the microscopically-short fuse of youngsters with bipolar disorder. She says: "Anger is an emotion we all experience...if you get fired from a job, you get angry...if a car runs a red light and narrowly escapes slamming into you, you may feel angry. The anger associated with bipolar disorder in children is different. It is an internal state that requires no outside prompting. It has a fuel all its own. This internal anger is so reactive but with higher intensity and less restraint."

One of the children we interviewed for our book gave a fascinating description as to how he feels when a rage gathers. He explained:

It comes out so quickly; faster than a knee-jerk reaction. It's like electricity shoots through me. It's like being struck with lightening. I feel rage and hurt and a need to strike back. I would be raging every day, multiple times a day, verbally abusive, nasty, negative, but very careful not to show it to the outside world.

A teenager described her rages this way:

I used to go to my room and punch the walls and I couldn't stop crying. It was like a dream you couldn't recover in the morning: You know something bad and worrisome has been a concern somewhere in your brain, but you just can't remember it.

Most of the children are so remorseful after these affective storms, that one mother told us that "His remorse is more heartbreaking than his rages."

Certainly there is something poorly regulated in the central nervous system of most children with early-onset bipolar disorder. So many of the children have sensory integration problems, exaggerated stress responses, elation and irritability, depression and low energy states, poor impulse control, and low frustration tolerance, that it is no wonder that the confluence of these states and traits culminate in aggressive rages.

Because these children are so proud and often manage to keep it together in the outside world, people don't believe that this charming child can turn so quickly in the home environment, and they are apt to jump to the conclusion that the child is manipulative, or that the mother is igniting the problem, thus placing a double burden on the already-abused mother.

It is more likely that the emotional ties to the mother are so intense and these children are so uncomfortable in their own minds and bodies that they unreasonably expect her to reestablish a harbor of safety, all the while withstanding their aggression.

One 14-year-old boy told us that the thing that infuriates him more than anything when he's raging at his mother is when she turns away or does not look at him kindly. He cannot see that his actions are the catalyst of the painful encounter. When she turns away, he feels abandoned to his terror and loss of control. His mother should do something to lessen his overwhelming fear and to demonstrate her concern for his safety and protection.

Indeed, a sense of threat seems to pervade the waking and sleeping hours of these children, yet they are too proud to show their fear to the outside world and reserve it for the one person they know will never walk away-their mother.

(Split Screen): Not all children tantrum and rage, but whether they do or not, most are prone to boredom. They can't seem to get invested in anything and whine and complain constantly about being bored. Because the children feel helpless and so often out-of-control, they desperately need to reconnect and escape from the intolerable feelings inside. Often they become provocative-they shake things up with other people to add that much needed spark that makes them feel involved and in control. They may tease and annoy a sister, or cause a brother to lose at Nintendo. They leave chaos in their wake. Meantime the mother gets to play bad cop and camp counselor all at the same time to redirect her very bored, disaffected youngster. (Video games and television may be the only activities that bring some peace into the household as someone has to prepare dinner or at least set the table for take-out food and oversee the homework and activities of the other siblings.)

6:00

Dinner:

This can be dicey as the youngster may be involved watching television, playing Nintendo, and not be easily disengaged or transitioned to the dinner table. Parents have a choice: they can demand the child's presence, thus risking a full-scale blow-up; or decide that they have to pick their battles and it's more important to have a pleasant dinner with their other children.

Some evenings all will flow smoothly; others will quickly disintegrate. Parents have to learn to live with the extraordinary unpredictability of their children's behaviors. One father explained: "Things can be going along smoothly and then something would anger him and an attack would start for hours on end. We tried never to let our guard down, but he was often so charming and sweet that we would constantly express surprise when it happened. We are always walking on eggshells."

7:00

Homework:

The time to sit down and organize and concentrate in order to do homework often coincides with periods of rapid cycling that can begin in the afternoon and early evening hours. The moods of the children cycle upwards: they become silly and giddy, their thoughts race, and it's nearly impossible to get them to concentrate on homework assignments. And, as we saw earlier, any demand to return to an arena that is difficult and frustrating is bound to raise resistance and opposition.

Parents become extremely anxious about the work that will go unfinished and the children will score badly on tests (thus reinforcing their already-low self-esteem and demoralizing them even more). They also fear that the teachers will frown on their parenting skills. (Note: We have found that once teachers understand what is happening for the child and family, they do everything to help out. However, the teachers cannot be left in the dark as to what is happening to the child in the after-school and evening hours.)

9:00

Time For Bed:

Despite the parents' best efforts to establish a slow-down of the day and to help settle the child for sleep, two factors will work against this happening: As we mentioned above, the minds and bodies of these youngsters are more active in the evening hours; and many of them are absolutely terrified of going to sleep.

They are prone to night terrors where predators stalk them, chase them, and kill them or their families in particularly violent and horrific ways. "I was being chased by a masked shadowy man and I got to the stoop of my house, and he kept stabbing me in the back-over and over," said one boy "Or, I am being chased by headless men who are going to eat me."

Blood and death and dismemberment appear often in the dreams. One little girl told her mother that she dreamed that something very scary was pulling her under her kindergarten room, as blood began to flood the floor of the classroom. Many of the pictures these children draw in the daytime reflect themes of pursuit, weapons, and blood dripping from severed limbs and lopped off heads.

With such emotionally-charged imagery attaching to the dream state throughout the night, is it any wonder that these children are so often in combative and irritable modes during the day, and that they are absolutely terrified of bedtime?

Parents spend hours at their children's bedsides at night trying to reassure them and make them feel safe and protected. Most of the younger children eventually sneak or force themselves into their parents' bedrooms as they are too afraid to stay in their rooms alone.

Meantime, marriages are placed under heavy strain. The sheer exhaustion of having to deal with all of this (and the doctors' appointments, the trips to the pharmacy, the huge expenses, the guilt about the other siblings, and the fears of what the outside world is thinking of them) leaves the parents with little time or energy to develop plans for their own needs and pleasures in life.

6:30 AM

A New Day Dawns

We hope that this snapshot of "a day in the life" generates understanding and compassion for the child who must tolerate this emotional turmoil and its consequences, and for the parents who are trying desperately to help their children and keep their families together.

Unquestionably, proper medications smooth out the cycling patterns, inhibit the rage reactions that seem so out of proportion to their triggers, and help dampen the period of activation that so often occurs in the late afternoon and evening hours. Therapists can help the children with many of their anxieties and fears and often-ill-fated social interactions, as well as help them scale back their extreme responses to people and events. Understanding educators can "take the hand of the child" and help relieve the worries of their days.

With everyone's help, the ice upon which these children and their families skate will not be so extremely thin.

We'll write again soon, but before we sign off, we'd like to tell you how pleased we are that the third edition of The Bipolar Child will be published this August by Broadway Books. This new edition is significantly expanded and covers the many changes that have taken place in the field of pediatric bipolar disorder in the past few years.

It is our hope The Bipolar Child, Third Edition will be extremely helpful to you and your children, and to their educators and treatment teams.

As always, we look forward to hearing from you.

All best,
Janice Papolos and Demitri Papolos, M.D.

Bibliography

Anglada, Tracy. Intense Minds: Through the Eyes of Young People with Bipolar Disorder. Victoria, B.C.: Trafford Publishing, 2006.

Papolos, Demitri, and Janice Papolos. The Bipolar Child, Revised and Expanded Edition. New York: Broadway Books, 2002.

At a recent conference on pediatric bipolar disorder, the topic of the seasonal aspects of the illness came up and caused a flurry of nods from the parents in the audience. These parents were aware that, despite the extraordinarily rapid daily shifts in mood, their sons and daughters did indeed have a depressive slump that began (often insidiously) in September, and sadly became fact by November or December. But, come the days of late February and March when the photoperiod lengthens and there are days punctuated by abrupt temperature changes, the parents noted a pick-up in activity and the stirrings of mania. They wryly dubbed this springtime phenomenon "March Madness."

When it was suggested that a careful tweaking of medications as a pre-emptive strike during these periods of vulnerability be considered, one mother commented: "But I thought once you finally get them stable, you don't dare touch the medication dosing or levels."

We understand her thinking. Stability comes at such a very high price: so many hard-to-withstand (and witness) side effects; so much sadness and fear for the child whose pain is unrelieved or exacerbated by a failed medication trial; so many hopes dashed... Once the child really stabilizes, who would want to rock that boat?

Yet the boat rocks for many, given the nature of the change in seasons; and children and adolescents with bipolar disorder are that much more sensitive and reactive to seasonal change. Break-through depressions and manias are commonplace, and can usher in periods of instability. These seasonal vulnerabilities must be taken into consideration in the long-term treatment strategy.

The Historical Understanding of Seasonality in Bipolar Disorder

Since ancient times, remarkably regular seasonal recurrences of depression and mania have been an intriguing, but unexplained phenomenon. Hippocrates, in the fifth century, considered mania and depression to be disorders of spring, while Pinel in the 1800s wrote that "maniacal paroxysms generally begin immediately after the summer solstice...and continue during the heat of summer, and commonly terminate towards the decline of autumn." Kraeplin, considered the father of biological psychiatry, documented seasonal episodes of illness in some manic-depressive patients with a preponderance of manic episodes in the spring, and depressive episodes in the winter.

Norman Rosenthal, M.D., a pioneer in light therapy for depression wrote in his book Seasons of the Mind:

The effects of the seasons on humans were all well known by the ancients, but have largely been forgotten by modern medical practitioners. Their importance has been kept alive only by artists, poets, and songwriters. Shakespeare, for example, observed that "a sad tale's best for winter," while Keats wrote of a nightingale "singing of summer with full-throated ease."

In the past 25 years, science has caught up with the arts, and the medical importance of the seasons has been recognized anew. Surveys have shown that people experience some alteration in mood or behavior with the changing seasons, and, for as many as one in four, these changes present a problem.

A study of hospital admission rates for mania in Great Britain showed a high correlation between seasonal changes in mean monthly day length, daily hours of sunshine, and daily temperatures that correspond to the vernal and autumnal equinox.

Many children not only experience seasonal perturbations of mood, but their hour-to-hour daily variation of mood and energy change as well. During the fall, they often experience lower energy levels throughout the morning, increased irritability, greater anxiety, and lower frustration tolerance. Conversely, the evening period of activation is diminished. During the spring, this pattern is often reversed.

One mother, when writing of her young son's seasonal mood variations said:

Oliver definitely has seasonal mania. Starting in March, when the light begins to change, his sleeping patterns go out of whack. The child who slept in the winter months like a hibernating bear, is suddenly wide-eyed at 5 A.M., or even earlier. He is up, fully dressed for school, and standing by our bedside with an armload of truck picture print-outs (his obsession), chattering about when the latest model of this or that is coming out, wholly unaware that it's the middle of the night and people are supposed to be sleeping.

Sometimes he keeps right on going through his day, seemingly unaffected by the lack of sleep. Other times, the burst is short, and he crashes on the couch. Then we need a forklift to get him up for school. This happens in the fall as well. November / December is always a difficult time. This period is a little different, though, because he can also be more irritable, oppositional, perseverative, which we don't see quite as much in the spring. We are acutely aware of these seasonal swings.

In a 2005 study published in the Journal of Affective Disorders, Dr. Shin Schaffer and colleagues at the University of Toronto, looked at a community sample of five diagnostic groups: normal subjects, those with non-seasonal depression, seasonal depression, non-seasonal bipolar disorder, and seasonal bipolar disorder. They found that individuals with bipolar disorder experience greater seasonality than those with depression only, or healthy controls.

These seasonal fluctuations have important implications for the management of bipolar illness: the levels of medications that previously produced stabilization, may not be as effective during these periods of change in the light/dark cycle. For many children and adolescents with bipolar disorder, stability begins to wobble or come undone as surely as March follows November. Why should this be so?

The Biological Underpinnings

Many biological mechanisms anchor human beings to the passage of time and influence our behavior. The timing of events within the central nervous system is at least as important as the special arrangements of the central neuronal activity in the brain. Neurotransmitters, neuropeptides, and hormones must not only lock into their corresponding receptor keyhole, but they must act with appropriate timing - in relation to one another and to periodic events in the environment.

Today, scientists accept that a kind of biological clock in the human organism establishes a fundamental daily rhythm for bodily functions such as temperature, the release of cortisol, rest/activity cycles, and the secretion of melatonin. But nature has built some flexibility into a human being so that the body can adjust to the ever-changing environmental rhythms such as longer and shorter days in the summer and winter.

Apparently some people do not adjust so easily.

Dr. Alfred Lewy, director of the Sleep and Mood Disorders Laboratory at Oregon Health and Science University, hypothesized that certain people with depression have a desynchronization in their 24-hour internal clock rhythms. For instance, their sleep, temperature, and cortisol cycles may be in synchrony with each other, but be out of step with other 24-hour rhythms, thus causing their internal rhythms to run a few hours behind or ahead of schedule. They either start and stop releasing melatonin earlier than usual (leading to evening sleepiness and early-morning awakening), or start and stop releasing melatonin later than usual (leading to difficulty sleeping at night as well as difficulty getting up in the morning).

The idea that depression and mania can result from abnormalities of photoperiodic regulation draws support from the known therapeutic effects of bright light treatment in seasonally-cycling bipolar patients, as well as from Dr. Lewy's studies. He found that, compared to nonbipolar subjects, bipolar patients exhibited an abnormality in their capacity to suppress melatonin when exposed to bright light, suggesting that these patients may be more sensitive to the effects of changes in the intensity of light and to seasonal changes in the photoperiod.

The steady, measured effects of the clocks that time us and the capacity to adjust to ever-changing light/dark cycles, and ambient temperature fluctuations, may be perturbed in kids with bipolar disorder.

Seasonal Depression and Light Therapy

In 1984, Dr. Norman Rosenthal, then of the National Institute of Mental Health, published a ground-breaking article about the seasonal pattern of depression and bipolar disorder that he coined "Seasonal Affective Disorder" (SAD). Seasonal Affective Disorder is today described in the DSM-IV as a "regular temporal relationship" between the onset of major depression and the time of year (fall or winter), accompanied by a full remission (or change to mania or hypomania) in the spring.

Dr. Rosenthal reported on the positive reactions of depressed patients when they were exposed to bright light therapy on a daily basis in fall and winter days: Their symptoms of depression improved.

Today, the therapeutic value of light therapy is readily acknowledged. A 2005 systematic statistical review - a meta-analysis - of 20 randomized, controlled studies previously reported in the literature, showed that light therapy using light boxes or dawn simulators was as effective as conventional medications for the treatment of seasonal depression.

Since children with bipolar disorder often slide into autumnal and winter slumps, close monitoring of this potential pattern of annual relapse needs to be documented. Usually, if a pattern is recognized, the occurrence repeats itself, sometimes to within a week year-to-year. Light therapy tends to work better as a preventative treatment; so knowing the periods of vulnerability affords an opportunity to intervene in advance.

What Are Light Boxes and Dawn Simulators?

A light box is a metal fixture approximately two feet long and one and a half feet high. It contains ordinary white fluorescent lightbulbs set behind a plastic diffusing screen, which becomes a film that filters out most of the ultraviolet (UV) rays from the bulbs.

Typically, the light emitted from these boxes varies between 2,000-to-10,000 lux in intensity. (Lux is a unit used to measure the intensity of light. Indoor light levels range from 200 to 700 lux; outdoor levels on a sunny spring day range from 2,000 to well beyond 10,000 lux.)

A child should sit approximately one to two feet from the light source and look up for a few seconds towards the light every several minutes or so. A youngster can play video games in front of the light, watch television, or read.

Initially, one has to be cautious about reaching an effective daily duration of exposure - usually 20-to-30 minutes. Rarely, less than 10 minutes may trigger a brief period of activation which is readily abolished by reducing the duration of exposure.

It is thought that early-morning treatment is optimal, but given the sleep inertia these children and adolescents suffer (see The Bipolar Child Newsletter called "The Morning Battleground" at http://www.bipolarchild.com), afternoon therapy may be just as therapeutic for some children. We also know parents who install a light box in the resource room of their children's schools and they receive the therapy while working with the resource teacher.

A dawn simulator is a small electronic timer that can be plugged into an ordinary bedside lamp with a 60- to 100-watt-intensity bulb. It can be programmed to create an artificial dawn lasting between sixty to ninety minutes. In other words, if your child has to get up at 6:30 A. M. to make the school bus, the timer should be set at 5:00 or 5:30 A.M.

There are many manufacturers of light boxes, but three reliable manufacturers are: Apollo Light Systems; Northern Light Technologies; and The Sunbox Company.

Light boxes cost somewhere between $160 and $300; and a dawn simulator costs approximately $150. Some insurance companies may pay for light boxes and dawn simulators if the child's doctor writes a letter detailing its medical necessity.

Special Seasonal Considerations with Lamictal and All Mood Stabilizing Treatments

Treatment strategies may need to be revised during these periods of seasonal vulnerability. The doses of some medications may need to be adjusted upwards or downwards, depending on the attributes of the drug and the pattern of seasonal symptom change.

If springtime mania is a part of a child's calendar year, than most mood stabilizing agents and atypical neuroleptics with antimanic properties may require upward adjustments in dose. Certainly, obtaining serum levels prior to peak periods of vulnerability will alert vigilant clinicians to the need to adjust dosages as a protective measure and potentially abort an unwanted seasonal recurrence of symptoms.

Special consideration for the anticonvulsant-mood stabilizer, Lamictal (lamotrigine), may be warranted, given its unique antidepressant properties. The drug is frequently effective for controlling rapid-cycling and mixed bipolar states, but, unlike other mood stabilizers that work most effectively against acute mania and prevent future episodes of mania and depression, Lamictal has robust antidepressant effects that work in the depressed phase of the disorder. This attribute, however, can produce activation as the photoperiod shifts to longer daylight hours. Thus, the Lamictal may need to be lowered in advance of the shift of seasons in order not to induce or exacerbate breakthrough agitation and irritability that accompany a resurgence of hypomanic or manic symptoms. A reduction of only 5 to 10 mg may suffice; but some children may require a larger decrease in their daily dose.

Clinically, a similar phenomenon has also been observed with bright light treatment. A reduction in duration of exposure to light by even 10 minutes may avert activation.

We spent time, recently, with a man who was discussing his bipolar disorder and his treatment regimen. He said that Lamictal had been a miracle drug for him; it had given him back his life. But about eight months later, he told us, it had stopped working. When we asked him what month he noticed the Lamictal "punk out," he responded, "In April. I became increasingly speeded up and manicky, so I had to go off of it." (He was so relieved to learn that a reduction of the dose in the early spring may have averted the hypomania, and that he can possibly restart the medication in the early fall so as to avoid his lifetime pattern of fall and winter depression.)

A month after that conversation, the mother of a 14-year-old son who was taking Lamictal told us:

Henry was doing so well through the fall and winter - better than he's ever been - but around mid-March he got very agitated, unreasonable, and physically aggressive, and it just kept getting worse. He was flipping the coffee table over, destroying other pieces of furniture, and he said to me: "You have to do something; I don't feel I can make it stop!"

I suspected it was the Lamictal, as I am on it myself. It has made a huge difference in my life, but I know that I become speeded up in the spring, and my doctor lowers the dose. Henry's doctor lowered his dose of Lamictal as well, and raised his Risperdal for just a few days. Each day we went in the right direction, and after a week we had our Henry back.

All dosages of all mood stabilizers have to be judged against the seasonal changes. The mother in the beginning of this newsletter who wrote about her son Oliver's seasonal changes said: "We are acutely aware of these seasonal swings, and we are always ready to increase his lithium in the spring. He goes back to his regular dose before September. Right now, in May, he is still in a pretty manic phase. We are now rechecking the levels."

Children are growing taller and putting on weight all through their growing up. Good clinical practice would be for the treating physician to look at the levels of the mood stabilizer before the lengthening days of spring and the shortening days of autumn and notate what levels produced stability. Then, preemptively, the doctor can reproduce those levels, which, due to the increase in height and weight, will no doubt need to be increased. There may be times where a slight increase in an atypical antipsychotic might need to be raised also to tamp down a tendency to swing too high.

A parent should be in close contact with the treating physician during the times of seasonal change.

In Conclusion

It is obvious that children - up against seasonal and growth patterns - are moving targets when it comes to treatment strategies. Because of the sensitivity these children have to seasonal change, treatments may have to be calibrated and adjusted to accommodate these vulnerabilities. Some children will experience instability if prescriptions and doses remain etched in stone.

It behooves all physicians and parents to examine the children's seasonal patterns and, if necessary, institute preemptive adjustments of the medications, or a trial of light therapy in the fall, to stave off breakthrough episodes that threaten stability.

So when parents ask "Is stability a possibility for children with bipolar disorder?" the answer may be that the correct medications, and careful consideration of seasonal vulnerability and timely medical interventions, certainly boost the chances.

As always, we enjoy hearing from you. May the summer days bring brightness and warmth to your households, and happiness and stability to your children.

We send you our best,

Janice Papolos and Demitri Papolos, M.D.

Acknowledgments

The authors wish to thank Cheryl Matalene and Karen Williams for their help in the preparation of this newsletter.

Bibliography

Golden, R. et al."The efficacy of light therapy in the treatment of mood disorders: A review and meta-analysis of the evidence." American Journal of Psychiatry 2005; 162:656-662.

Lewy, A, et al. "Bright light, melatonin, and biological rhythms." Psychpharm. Bull., 1986: 368-372.

Matalene, C. E-mail of May 18, 2005.

Papolos, DF. "Serotonin, Seasonality, and Mood Disorders" in The Role Of Serotonin in Psychiatric Disorders, edited by Serena-Lynn Brown and
Herman M. van Praag. New York: Brunner/Mazel, Inc. 1991.

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

Rosenthal, NE. Seasons of the Mind. New York: Bantam Books, 1989.

Rosenthal, NE, Sack, DA, et al. Seasonal affective disorder: a description of the syndrome and preliminary findings with light therapy. Archives of General Psychiatry 1984; 41: 72-80.

Williams, K. Telephone Interview of May 23, 2005.

One of the questions we asked on the initial survey for The Bipolar Child, concerned a craving for carbohydrates: did the child or adolescent crave starchy foods such as potatoes, breads, pastas, and macaroni and cheese? or sugary foods such as candy, cookies, and ice cream? We'll never forget the follow-up phone interview we had with a young woman who had indicated a craving for carbohydrates all through her childhood and into the present. As we asked her to describe the cravings, there was a giggle at the other end of the phone. She asked: "Would you consider a gallon of Breyer's chocolate chip mint every night a craving?"

She went on to tell us that her craving was so strong that she would buy half a gallon and eat it in the car and then go back to the store and buy another one. We asked if she kept a supply of plastic spoons in her car. She laughed out loud and said: "No, I would use my fingers. It was savage."

Adolescents have recounted pouring sugar straight out of the box down their throats; and mothers have told us that long ago they nicknamed their children "Carb King" or "Spud." We recently interviewed "Spud," but first we asked her mother to describe her daughter's tremendous intensity about eating potatoes. "What if she doesn't get them?" we asked. "It gets really, really ugly," she replied quietly. When we asked her what "ugly" meant, she said: "See what Katie will tell you. Katie will be totally honest about it."

We reached Katie on the phone and she explained:

Say I'm doing my homework, and suddenly I get a craving for potatoes. I shut down and can think of nothing else. I get into "mission mode" and start to worry: What will I do if I can't get them? I will be totally lost. Where can I go from here? I won't be able to get off this.

If my mother says: "I don't have potatoes, Katie, and I'm not going out in this weather to get them," I get really, really angry. Most of the times we have a huge screaming match, but sometimes I push her because I am so mad. I see my mother as my enemy because she's not supplying me with what I need. She is a total obstacle to what I need. The word "no" is evil. It is not acceptable.

She also said that after she storms off, she comes back 15 minutes later and apologizes because she can't believe she acted that way over a potato.

Katie isn't the only one who craves potatoes. The mother of a nine-year-old boy wrote to us and said:

As far as the carbs, he is a bread and mashed potato child. I almost force-feed him anything else. He would eat huge piles of mashed potatoes if I let him. He loves and gets obsessive about eating them, and during the mornings and evenings he is just ravenous and I almost have to follow him around to keep him from eating everything in sight - mostly bread, chips, and stuff. I don't keep a lot of sweets around for that reason.

Many parents report that their children are extremely finicky about the foods they eat, and some eat only white foods (bread, pasta, French fries, potatoes, and rice); or eat an equally narrow repertoire of food that consists of four or five items with a preference (or aversion) for certain textures. Some crave one kind of food to the exclusion of all others, and then, after a month or so, seem to lose all interest in eating it.

Parents watching their children's weight ballooning as the kids maraud through the kitchen day after day, night after night, wonder anxiously (and often with some level of disgust) what they can do to stop these gorging, out-of-control behaviors.

What Is Going On?

While it has long been known that adults who suffer Seasonal Affective Disorder (SAD) have a marked craving for carbohydrates in the winter months and are not as ravenous about starchy or sweet foods in the spring and summer months, there are no published studies about children and this phenomenon. However, when the researchers of the Juvenile Bipolar Research Foundation looked at a sample of over a thousand children at risk for, or diagnosed with bipolar disorder, over 65% of the parents endorsed the item "craves sweet-tasting food or carbohydrates" at a frequency rate of "often," or "very often or almost constantly." In other words, it wasn't always seasonal.

This would fit with the poor regulation of drives - particularly appetitive and acquisitive drives - seen so often in the childhood form of the disorder. Natural drives become obsessive and overwhelming and difficult to modulate. Although survival of the human species has depended on a sometimes hell-bent foraging and storing of food, this is natural instinct writ large and inappropriate for life today when supermarkets are often a block or two away, and refrigerators and cabinets typically boast an abundance of food.

The Biological Basis

The appetitive craving for carbohydrates is modulated by a complex cascade of neuropeptides, hormones, and the receptors through which they act and are acted upon in various feed back loops. One of these peptides, Neuropeptide Y (NPY), is thought to play a major role in the craving for carbohydrates.

Neuropeptide Y is produced by a dense cluster of cells inside the hypothalamus at the base of the brain known as the paraventicular nucleus. NPY is the most abundant behaviorally active neuropeptide in the brain. Studies show that injections of NPY into the ventricles of the brain, cause an animal to forage and to consume carbohydrates to the exclusion of all other foods.

Among the actions of central NPY, the peptide exerts an influence on neuroendocrine systems that regulate appetite, circadian rhythms, and. through effects on the hypothalamic-pituitary-adrenal (HPA) axis, the stress response that regulates the output of corticosteroids that, in turn, influence carbohydrate metabolism. Typical symptoms and abnormal behaviors that represent a dysregulation of appetite are carbohydrate cravings, binge eating, hoarding, bulimia, and anorexia-all commonly associated with mood disorders. Though tempting to anticipate, there is little direct evidence of altered functioning of NPY in such behaviors. Moreover, there are no clinical treatments yet that directly alter NPY functions.

The Sense of Deprivation

Remember Katie's telling us that she found her mother's "no" to her need for potatoes "unacceptable," and that she saw her mother as an obstacle getting in the way of what she needed?

Katie's mother's "no," or her inability to meet Katie's needs at that moment in time, catapulted her into a rage?

Children and adolescents with bipolar disorder 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.)

Something else stands out in Katie's comments: her worry that she would be lost if she didn't get what she needed and couldn't get past her fixation on the food: "What will I do if I can't get them? I will be totally lost. Where can I go from here? I won't be able to get off this."

Children and adolescents with bipolar disorder often have rigid and inflexible thinking. They get stuck, and they have difficulty estimating time and cause-and-effect, and become "prisoners of the present." Katie's anxiety about being trapped in time and space without access to the potatoes that are the source of her intense cravings, arouses irritability, and great fear as well as anger.

Hoarding and Hiding

A craving for carbohydrates leads to a number of behaviors that are manifestations of the appetite dysregulation that may help to define one aspect of the core syndrome of bipolar disorder in childhood. Those behaviors include foraging (going after and finding the food), binging and hoarding.

In the animal world, foraging and hoarding (provisioning for winter or famine) are necessary for survival. But many parents report dismay when they discover these hoarding behaviors when they simply move the beds in their kids' rooms. The space behind or to the side of the beds reveal caches of candy bars, potato chips, soda cans, and cookies. Empty wrappers are strewn around these "nests." The kids may be hoarding for a time when they may need immediate access to carbohydrates. It is part of the acquisitive drive and the appetitive dysregulation.

Katie hoards, and she doesn't hide her need behind the bed. She concocts this potato casserole (potatoes, cheese, and sour cream), and has to know that half of it is in the refrigerator in case she has a sudden craving. She guards this casserole aggressively. When we asked her what would happen if her younger brother decided to have a late-night snack of potato casserole, she laughed and said: "That would never happen. He is afraid of the wrath of Katie!"

Medication-induced Cravings

Not only do many of the children with bipolar disorder gain weight from constant binging, but, unfortunately, some mood stabilizing drugs and atypical antipsychotics can cause weight-gain (sometimes in alarming amounts and extraordinarily rapidly). Moreover, children seem to be even more sensitive than adults to the weight-gain effects of antipsychotic and other psychotropic drugs.

Some of the medications used to treat bipolar children cause an extreme, insatiable hunger. The mother of a boy on a commonly-prescribed mood stabilizer made a list of the fantastic amounts of food her son was eating in the first few weeks on the medication. In a few hours he consumed: five packets of instant oatmeal with tons of sugar on top, four potatoes, two cheeseburgers, two pieces of chicken, one hamburger bun, one piece of coffee cake, sixteen ounces of grape juice, and twenty ounces of Mountain Dew.

Some of the modern antipsychotic drugs, including olanzapine (Zyprexa), quetiapine (Seroquel) and clozapine (Clozaril, and generics), can be particular offenders for many children. We have heard of children gaining two pounds a day with certain of the atypical antipsychotic drugs. While it is not understood completely, one theory postulates that the degree of weight gain is correlated with the drug's affinity for histamine (H-1) receptors. Olanzapine and clozapine and quetiapine have greater affinity for H-1 receptors than do risperidone (Risperdal) or aripiprazole (Abilify). These drugs also seem to have synergistic effects on the H-1 receptors, as well as certain serotonergic receptors implicated in regulating appetite.

The hunger and weight gain do not happen to all children, but should be anticipated. Low-calorie snacks and drinks as well as an increased daily exercise schedule should be planned. Ideally, the child should be seeing a nutritionist who can explain all of this in a calm matter. Some physicians add the anticonvulsant topiramate (Topamax) to the medication mix in moderate doses, as this drug has appetite suppressant effects. However, its status as an effective mood-stabilizer remains uncertain, and it is not FDA-approved for that purpose. Other newer anticonvulsants, including zonisamide (Zonegran), may have similar appetite-reducing effects, again with uncertain effects on mood and behavior.

Light therapy in adults seems to have an effect on carbohydrate craving, but no studies of this phenomenon have been reported in the young.

Life in the Fast-Food Nation

Parents of bipolar children have the deck stacked against them in this country. Carbohydrate-dense fast food is so available on every street corner, as well as in the school cafeteria, that urges can be satisfied easily. Rapid increases in serum glucose levels result in subsequent rapid decreases, and this drop jump-starts intense carbohydrate cravings. Cycles of craving and binging, are easily set off in children who are already biologically primed for these cycles.

And these cycles, unfortunately, promote mood swings - even in people who don't have the disorder.

In director Morgan Spurlock's fascinating documentary film, Supersize Me, he limited his diet to three meals a day of McDonald's carbohydrate-dense food, intending to play out this experiment for a month.

Within days he was waking up feeling terrible, and, besides gaining 32 pounds over several weeks and almost destroying his liver, he suffered intense mood swings from the rapid doses of carbohydrates into his body, and the subsequent drop in glucose levels. "I feel sick and unhappy," he revealed mid-project, "and then I eat and feel really, really good. So good, I feel crazy."

Referring to his cravings, the doctor monitoring the experiment told him: "You're craving these foods; they have become a drug for you."

The pursuit of carbohydrate-dense food that many of the children experience is so difficult for parents to combat - and not just because of Neuropeptide Y and other chemical cascades.

Mr. Spurlock's documentary points out that the average child in America sees 10,000 television commercials a year advertising sugary cereals, soft drinks, fast foods, or candy. By the time children can speak most of them can say "McDonald's."

When the director assembled a group of teenagers and adults (with the White House as a backdrop), they stumbled through the Pledge of Allegiance, but they could quickly recite the theme tag of McDonald's and other fast-food establishments. Children in America are subliminally primed to crave junk food, and this reinforces the innate longing for fixes of carbohydrate-dense foods in children and adolescents with bipolar disorder.

So What's A Parent to Do?

A friend of ours with a fifteen-year-old teenager who had early-onset bipolar disorder put her ideas into an e-mail. She wrote:

We've been battling the carbohydrate-addiction problem for years. We see his urgent need to eat certain foods, and we wonder if the meds are pumping up his appetite or the disorder itself is causing the compulsion to eat. We see the same "mission mode" around foods that we see in so many other areas of his life. In fact, our parenting sometimes feels like 24-hour mission control.

The food thing, though, seems most important because obesity is such a health risk and can do so much to damage self-esteem. I don't think there's a perfect solution, but there are a few little strategies that we've found helpful.

One is to limit - not eliminate - availability of binge-provoking foods. For example, Jeremy loves these certain cereal bars. They're not bad things to eat, it's just that he can't eat just one or even two. I don't want to have a situation where the rest of the family can't have anything in the house because we're trying to keep Jeremy from eating. So I still buy the things that are enjoyed. But I put most of them away in a cabinet in the garage where he'll never look. I take a few items from the box and put them in the kitchen pantry, one per day per kid. That way I can keep my eye on the quantity consumed without totally depriving.

It's like bird-feeding. You put a little seed out on the platform, and when it's gone you replenish it.

Jeremy's mother (and Katie seconded this) feels that a small meal before dinner is helpful. Jeremy's mother said:

I require him to eat a fruit or a vegetable or a salad before he starts the main meal. That way he fills up a little before digging in to the meat and potatoes. I know people who try to cut out the carbs, and believe me, it doesn't work. It leaves him feeling too unsatisfied and angry.

After the meal, we sometimes impose a waiting period before any dessert. Sometimes he gets involved with the computer and forgets all about it for quite a while.

Despite all these steps, he's still overweight to one degree or another. There are seasonal ups and downs. He loses in the summer and gains toward the winter, like a bear before hibernation. He can't regulate his cravings, and our job is to be his regulators. But really, you can only control so much.

She closed by saying:

Bottom line, I think we have to be realistic and not rigid. Sometimes I think it's okay for our parenting to have more give. Winter is not the time to crack down. In the summer there are more opportunities for constant exercise and for distractions from the obsession.

It's important that we all keep our sanity - right?

In Conclusion

When we spoke to Katie in a follow-up phone call, we briefly mentioned a few of the biological factors that might be at play concerning her overwhelming need for carbohydrates. She liked the idea that there was something called Neuropeptide Y, and that the cravings didn't necessarily mean she was willful or horrid, or that she was necessarily trapped and couldn't find a better way to resolve the problem.

Her mother also seemed to relax after she read this newsletter, and gained some sympathy for Katie's problem. She thinks she can be less angry and more tolerant of Katie's irrational demands, which are, after all, not of her own choosing.

We'll write again soon. Meantime, at this time of mid-winter and always, we wish you and your children the best,

Janice Papolos and Demitri Papolos, M.D.

The authors wish to thank Cheryl Matalene, Heidi Rochon, and our absolutely charming Katie for their astute discussion of this problem. A special thank you to Ross J. Baldessarini, M.D. who stands at our side with such wisdom.

References

Allison DB, Mentore JL, Heo M, Chandler LP, Cappelleri, JC, Infante MC, Weiden PJ. "Antipsychotic-induced weight-gain: A comprehensive research synthesis." American Journal of Psychiatry 1999; 156: 1686-1696.

Allison DB, Mentore JL, Heo M, et al.: "Antipsychotic-induced weight-gain: A comprehensive research synthesis." American Journal of Psychiatry 1999; 156: 1686-1696.

Berman K, Lam RW, Goldner EM. Eating attitudes in seasonal affective disorder and bulimia nervosa. Journal of Affective Disorders. 1993; 29: 219-225.

Christensen L.: The effect of carbohydrates on affect. Nutrition. 1997;13: 503-514.

Ishi T, and Elmquist, JK. Body weight is regulated by the brain: a link between feeding and emotion. Molecular Psychiaty,2005: 10:1-15.

"Katie." Telephone Interview of January 15, 2005.

Matalene, C. E-mail of January 18, 2005.

McIntyre, R., DA Mancini, and V S. Basile. "Mechanisms of antipsychotic-induced weight-gain." Journal of Clinical Psychiatry 2001; 62 (Suppl 27): 23-29.

Meyer, JM. "Effects of atypical antipsychotics on weight and serum lipid levels." Journal
of Clinical Psychiatry 2001; 62 (Suppl 27): 27-34.

Neuropsychopharmacology: The Fifth Geenration of Progress. Edited by Davis KL, Charney D, Coyle JT, and Nemeroff C.Philadelphia: Lipponcott and Wilkins. 2002.

Oommen KJ, Mathews S. Zonisamide: a new antiepileptic drug. Clinical Neuropharmacology 1999;22: 192-200.

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

Rochon, H. E-mail of January 13, 2005.

Does this sound familiar?

Yesterday morning it took an hour-and-a-half attempting to get him up. We kept shaking him, beseeching, threatening, beseeching anxiously.... We even called his cell phone thinking he might pick it up for a friend's call. He simply growled, muttered something we would have preferred not to hear, and turned over and went back to sleep.

We finally did see him rise from the bed and we ran the shower thinking that might wake him up. Ten minutes later we found him in the bathroom curled up on the bath mat, sound asleep.

A father detailed his family's three-stage morning routine with their six-year-old daughter:

I carry her downstairs to the living room sofa. I leave the room and my wife pulls off her pajamas and dresses her while she's still asleep (that's stage one). Stage two: We help her into the kitchen, although she's still very groggy, sit her in a chair, and give her an "injection of breakfast" by shooting a GoGurt (yogurt in a squeezable tube) in her mouth. Stage 3: We carry her to the bathroom and help her brush her teeth, etc. Then we put on her coat and go outside and wait for the bus (or shall we say, the bus waits for us). Sometimes.

Every morning, in America and abroad, many parents of bipolar children wake up and experience dread as they prepare to get their children up for school. Contrary to cheery television commercials where families gather around quaffing fresh-squeezed orange juice, these parents often forgo that fantasy and mount a siege simply to get their children out of bed.

It's a tall order. While it may seem as if the child or adolescent is behaving in an oppositional manner, a great many of these youngsters actually suffer from something called sleep inertia.

What Is Sleep Inertia?

Sleep inertia is a transitional state of lowered arousal occurring immediately after awakening from sleep and producing a temporary decrement in any subsequent performance. Studies show that sleep inertia can last from a few minutes to four hours. Youngsters with bipolar disorder are far closer to the latter than the former. One 17-year-old girl described her attempts to get up in the morning this way:

I feel as though my insides are whining. I will do anything not to get up. Sleep is more important than anything in the world. I could sleep until 4:00 in the afternoon.

I never think about it from my mother's point-of-view. I don't think anything. When I do get to school (after much yelling by my mother and me back at her), I have my head on the desk until somewhere around 11:00 in the morning. Right before lunch I seem to truly get up.

Several factors are involved in sleep inertia. A child may be depressed and chronically tired, or the thought of facing the school day may produce waves of anxiety or panic, forcing the child to choose sleep or somatic complaints over the trial of going into the school environment. In many cases, the medications may be causing an early-morning sleepiness.

We do know that children with bipolar disorder have disturbances in the architecture of their sleep—they have sleep/wake reversals and are activated at night and slowed-down in the morning. There is considerable evidence in the adult literature to suggest that several elements of the sleep/wake cycle are altered in people suffering with mood disorders.

The Typical Architecture Of Sleep

Normally throughout the night a person experiences two kinds of sleep that alternate rhythmically. One is called rapid eye movement (REM) sleep, during which most dreaming takes place; the other (not surprisingly) is called non-REM.

Non-REM sleep has a four-stage development plan as revealed by electroencephalogram (EEG) sleep studies. Sleep typically begins the night with a light stage 1 sleep where the brain waves are small and fast. After approximately 30 minutes, the sleeper slips deeper into sleep as Stages 2, 3, and 4 of non-REM sleep progress. EEGs of Stage 3 reveal larger and slower brain waves. Stage 4 brain waves are large, slow, and regular and this is the deepest period of sleep.

After approximately 90 minutes, a brief period of REM sleep appears. This is the dreaming state and the eyeballs can be observed moving rapidly beneath the eyelids. A 90-minute oscillating pattern develops with REM sleep asserting itself for longer periods of time. The first 90-minute cycle might consist of 85 minutes of non-REM sleep and 5 minutes of REM, but by the time the fourth cycle rolls around, it might consist of 60 minutes of non-REM and 30 minutes of REM.

But all is not so regular. As Drs. Mark W. Mahowald and Carlos H. Schenck of the Minnesota Regional Sleep Disorders Center at the University of Minnesota Medical School have written:

The rapid oscillation of states or the inappropriate intrusion of elements of one state into another may result in the appearance of parasomnias (night terrors, restless leg syndrome, teeth grinding, sleep walking, and confused arousals). Given the large number of neural networks, neurotransmitters, and other state-determining substances that must be recruited synchronously, and given the frequent transition among the three states of being, it is surprising that parasomnias do not occur more often.

A significant number of children with bipolar disorder do seem to be suffering several of these parasomnias, especially night terrors and confused arousals.

It may be that children and adolescents are being asked to get up and go to school when they are in the deepest, slow-wave pattern of sleep. Sleep research has shown that abrupt awakenings during a slow wave sleep episode produce more sleep inertia than awakening in stage 1 or 2 when the brain waves are small and fast. Awakenings during a REM episode produces some sleep inertia, but not as much as awakenings during slow-wave sleep.

Research is also revealing that sleep inertia is more intense when awakening occurs near the trough—the low point—of the core body temperature as compared to its peak. Sleep/wake irregularities, as well as irregularities of the thermoregulatory system, contribute to sleep inertia.

Thermoregulatory Disturbances

Children with bipolar disorder often have irregularities in their thermoregulatory systems. They are hot all the time—even when the ambient temperature feels cold (often very cold) to everyone else. Parents struggle constantly to get them to wear jackets in winter. In addition, it is not uncommon to see their ears turn beet red.

Scientists have found that the rapid onset of sleep occurs when the blood vessels in the skin of the hands and feet dilate and cause heat loss at the extremities. This causes the core body temperature to lower. A group of researchers, Drs. Kurt Krauchi, Christian Cajochen, and Anna Wirz-Justice, noted this functional relationship between core body temperature and sleepiness, and hypothesized that the opposite would also be true: the constriction of blood vessels would raise the core body temperature and the human being would come to a state of wakefulness. (Think colder at night and the onset of sleepiness; and warmer in the morning and the onset of wakefulness.)

The authors write:

The circadian clock prepares the thermoregulatory system for vasodilation to begin in the early evening as sleepiness increases, followed by a drop in core body temperature. Even lying down increases sleepiness by redistributing heat in the body from the core to the periphery. Turning out the light is a complex cognitive and physiological signal that also leads to vasodilation. There is a tight correlation between the timing of the endogenous increase in melatonin in the evening and vasodilation, an effect that is mimicked by pharmacological doses of melatonin. Before bedtime, then, many overlapping events orchestrate the thermoregulatory overture.

Could irregularities in the timing of melatonin release—a peptide known to reduce core body temperature and induce sleep—be a factor in the increased activity level seen at night and the marked sleep inertia seen in the morning? Melatonin, produced in the pineal gland, is secreted into the cerebral spinal fluid at dusk and diminishes its effect at dawn.

The pineal gland is a small reddish-gray structure that sits near the center of the brain. Its name is derived from the Latin word for "pine cone" because early viewers glimpsed a resemblance. The pineal gland has a story of its own.

The Pineal Gland

All vertebrates possess a pineal gland, and in certain reptiles and birds the gland is situated close enough to the top of the skull to monitor the intensity of sunlight. This "third eye" appears to help animals adjust to changes in the day-light cycles of the yearly seasons. Seventeenth-century philosopher Rene Descartes, thought the human pineal to be the seat of the rational soul; early 20th-century scientists felt that the buried-down-under human pineal had been abandoned by the roadside of human evolution.

Not so. In the mid-sixties, researchers discovered that the pineal gland secretes an important hormone called melatonin. As we mentioned above, it is a sleep-inducing hormone thought to have a part in the synchronization of circadian (daily) rhythms. In animals, melatonin influences seasonal breeding patterns. Its secretion is at the highest levels in winter.

Today scientists accept that a kind of biological clock in the human organism establishes a fundamental daily rhythm for bodily functions such as temperature, the release of cortisol, rest/activity cycles, and the secretion of melatonin. But nature has built some flexibility into a human being so that the body can adjust to the ever-changing environmental rhythms-such as longer and shorter days in the summer and winter.

Apparently some people do not adjust so easily. Dr. Alfred Lewy, director of the Sleep and Mood Disorders Laboratory at Oregon Health and Science University, hypothesized that certain depressed people have a desynchronization in their 24-hour internal clock rhythms. For instance, their sleep, temperature, and cortisol cycles may be in synchrony with each other, but be out of step with other 24-hour rhythms, thus causing their internal rhythms to run a few hours behind or ahead of schedule. They either start and stop releasing melatonin earlier than usual (leading to evening sleepiness and early-morning awakening), or start and stop releasing melatonin later than usual (leading to difficulty sleeping at night as well as difficulty getting up in the morning). Exactly what is seen so often in children with bipolar disorder.

What Can Be Done About Sleep Inertia?

A good plan of attack would be to discuss the timing of medications with the treating physician. If one or more of the meds is contributing to morning grogginess, than it might help to administer the drug at an earlier time the day before. If anxiety is causing school refusal, the doctor or therapist may ease the fears of the child by helping him or her deal with the anxiety. Cognitive therapy may be particularly helpful.

It is important that parents and teachers recognize that many children with bipolar disorder have co-occurring learning disabilities and executive function deficits, and that these deficits make school embarrassing and dispiriting. Rather than get up and go to school and fail, the youngster may prefer to sleep. Neuropsychological testing will reveal these problems, and the IEP of the student can accommodate these disabilities and make the child or adolescent less anxious.

Phototherapy, or light treatment, may entrain the rhythms and phase shift the dysregulation many of these children have. Some parents have reported that a dawn simulator is helpful in getting their children out of bed.

If the prescribing doctor thinks a trial of melatonin is a good idea, he or she will discuss the timing and dosage. In a pilot study, one of the authors of this newsletter (D.F.P.), found that 3-6 mg of melatonin given approximately 20 minutes before bedtime, not only enhanced the earlier onset of sleep, but in a number of cases abolished sleep-arousal disorders such as night terrors. A more restorative sleep ensued. Since melatonin is known to lower core body temperature, this may explain one of its effects on the regulation of the sleep/wake cycle.

Remember the parents who had to squirt GoGurt in their daughter's mouth each morning? They told us that they began to give her melatonin each night and she can now get up, get dressed, and eat without the aid of her parents (and Gogurt is no longer the only staple of her morning menu).

Melatonin requires more study, and no one is certain of its long-term effects, nor will it work for everyone. Naturally, much depends on the causes of the sleep inertia.

Until the sleep/wake cycle is regulated (and your child may always be more of an owl than a lark), an accommodation in the school day may have to be made. It might help if the student is allowed a later start, and it would be wise to schedule all academics later in the morning and in the afternoon when he or she would be more cognitively available for learning.

During the writing of this newsletter, a mother emailed us her philosophy and mantra. She speaks of her "during the school-year child" and her "summer vacation child." Because her son has learning disabilities, as well as sleep inertia, he feels anxiety, and even has small panic attacks upon arriving at school. She wrote:

Each school morning for me, as a mother, is an adventure. I try not to worry in advance because I never know what each morning will bring me from my son. Is it a good morning for him, or a bad morning? I only find out when HE finds out.

I try not to get anxious or too pushy, but of course sometimes I lose control, especially if there's a meeting I absolutely can't miss, or if I have a doctor's appointment.

I need to be aware of myself, my attitude, my temper, even my breathing. I do my best to slow down, speak reasonably, and gently, and offer whatever alternatives work. I have even been known to offer bribes because I know that once he gets to school, his anxiety usually evaporates and I receive reports later about "what a good day he had." I need to look at a bad morning as not necessarily a permanent all-day condition.

She concluded by saying:

So my Mom mantra for a school day morning is: (1) Greet each day as a new day. (2) Prepare for different contingencies. (3) Maintain my calm, no matter what. (4) The more agitated my son gets, the calmer, slower, and gentler I get. (5) Take my time: it is more important for him to get to school, than it is important that he get to school on time. (6) Learn to cut my losses, and give up on the day if necessary. (If my son gets too agitated, I have to learn that it's not the end of the world if he doesn't get to school that day.)

In my opinion, it's hard to give consequences for behavior that is brain-induced or slowed down by meds. We just try to impress upon him what we expect from him, what the school expects from him. It can be a moment-to-moment experience.

In Conclusion

From all of the above, it is easy to surmise that morning alertness is dependent upon a complex set of factors: side effects of medications; chemical cascades that affect sleep architecture, thermoregulation, and mood; as well as the subjective feelings of the child when that morning alarm rings—anxiety, depression, or stress. No one can predict any one factor, several may be contributing, and all must be examined in order to find a solution for the child. The school administration and IEP team must understand the biological and psychological factors at play and accommodate the morning difficulties which, after all, are not volitional or oppositional on the part of the child.

We hope the above discussion helps parents who dread the split-second timing of a school morning, realize that they are not alone, and that they are not inadequate if the morning is tumultuous. For a while, at least, it is going to have to be okay if the child goes to school without breakfast, or leaves looking like he or she has just rolled out of bed (which he or she probably has).

Hopefully one of the suggestions above, and an understanding of what may be happening for the child at reveille, will result in a less gut-wrenching start to the day.

We'll write again soon. Meantime, let us hear from you. We both wish you and your children more gentle mornings.

All best,

Janice Papolos and Demitri Papolos, M.D.

Bibliography

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

Papolos, D. and J. The Bipolar Child, Revised Edition (Chapter 11). New York: Broadway Books, 2002.

Papolos, J. and D. "Night Terrors." The Bipolar Child Newsletter, July 2000, Vol. 4 (www.bipolarchild.com).

Reiter, R. "The Pineal Gland: An intermediary between the environment and the endocrine system." Psychoneuroendocrinology 1983; 8: 31-41.

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The authors wish to thank: Samantha Burch, Sharon Solomon, Theresa and Brian Moldawsky, Penny Smith, and Karen Williams for their insight and help throughout the preparation of this newsletter.