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.


  1. I am so interested in your research and hopefully in the end we can do more to support children and adults with this terrible disorder. My son is thirty and this disorder has destroyed his life both physically and mentally. My life in coping and managing him has also been torn to shreds both personally and financially. My fear now is for my grandchildren. In reviewing the questionnaire so many of the items ring true. The sleep disturbances, sweet cravings, and the body temperature dis-regulation is uncanny.

    Thanks you for researching and investigating Bipolar Disorder so one day it will not be sp stigmatizing and end in as many deaths as it currently does. As my son says ” I am uncomfortable in my own skin”‘ I cannot live like this death has to be better.”
    To see the damage the mania has done to his physical being, hypertension, irregular heartbeat, anxiety, sweating, working until damage is done to body (third degree burns, disk replacement0 is heartbreaking, the relationships that are broken within the family and with friends and the remorse after impulsive actions made after days of no sleep cannot be put into words.

    The worst of it all is no one cares nor do they want to help.

  2. My son is nine. If I am not fearing for his future everyday, I am fearing for my younger children and mine. My heart is breaking out of my chest that such a young, amazing child could be this sad and angry. I feel like my heart bleeds for him to have one medication or therapist that can get through to him and help him live his life. I’ve read, researched, cried, slept, not slept, fought, and now I’m just tired. I want him to have a chance to succeed in life. He is so very smart, and just like any mother, I only want whats best for him. This research means so much, and I can’t honestly say there isn’t much I wouldn’t do to find a cure, or an effective treatment so I won’t have to worry about my son living his life till its meant to end on its own. God speed, and I will keep my fingers crossed.

  3. My five year old son has just been diagnosed on the downside of a manic episode. I have bipolar too, as does my mother. I hoped and prayed that this brilliant strong-willed boy would side step this illness. I am hopeful that he won’t have a life full of struggling. My first son is 23 and has been exhibiting the same symptoms since adolescence and refuses to take meds. His life has been so hard. I am grateful and horrified at the same time that we have an answer to what’s been going on. I hope this research will help him so he doesn’t have to struggle as hard as the rest of this family has.

  4. Reading your books and finding the website have been a God-send… an answer to prayer … a miracle… and my new mission! In 2007, Hubby and I took placement of three of my distant cousins. CPS-Texas said they were all fine and had no problems. WRONG! As it turns out, all three have a list of DX that looks like alphabet soup! Struggling to figure them out and find some credible, professional help led me to your book. Wow! Finally, here was at least part of the answer. I now use the book to help educate counselors, pediatricians, and psychiatrists.

    Meanwhile, we’re trying to pick up pieces of what’s left of our lives. If only we’d been told all that the caseworkers knew. If only we’d been given a chance to prepare. If only ….

  5. I am glad I found this site. This research looks very interesting and describes my daughter to a T. I have been told by many that she shows signs of being bipolar but cannot be diagnosed until she is older. She has been diagnosed with ADD, ODD, mood disorder, depression, and anxiety. She has been on so many different medications and with some research it looks like most of them are the wrong ones. I will be interested to read more about this research.

  6. I pray for your son! Have you tried Depakote? It has been a life saver for my son!!!!!!

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