Research Update - juvenile bipolar disorder
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Dear Friend,
                                                      
The findings of our recently concluded Sleep, Activity Patterns, and Temperature Study provide evidence for what may be the first physiological marker for a psychiatric condition.  Why is this important to the JBRF community? Because it narrows the focus of our research to a specific part of the brain, and may lead to novel treatment approaches.

Children who have the Fear of Harm type of bipolar disorder exhibit symptoms that relect high levels of fear as well as defensive or reactive aggressive behaviors, and dramatic shifts in states of arousal:

  • intense fear of harm coming to self or others
  • territorial aggression/hoarding
  • particular sleep disturbances
  • parasomnias
  • overheating despite neutral temperature

The children who fit this phenotype share some common traits: they have difficulty settling at night and difficulty getting to sleep once in bed, they sleep fitfully and/or awaken throughout the night, and they have difficulty arising in the morning. 

A growing body of research has demonstrated that all of these sleep-related issues are associated with disruptions in thermoregulation.  While the relationship between the ability to sleep well and body temperature has long been known, a robust series of recent research studies has shown that when temperature regulation is disrupted, problems with both sleep and arousal/wakefulness occur.  Now, for the first time, we have data showing that:

  • thermoreguation is disrupted in children with FOH, and
  • sleep quality is decreased as a result. 

In the study, children with the FOH phenotype were compared with healthy control children.  The investigators found that an inability to dissipate heat at bedtime was strongly correlated with sleep onset latency.  Skin temperature from the chest and from the lower leg were measured throughout the night, and the gradient, or difference, between these temperatures was calculated each minute.  The childrens’ sleep was recorded using wrist-worn activity monitors. 

Typically, when a person lays down for bed, leg temperature will increase in parallel with decreases in chest temperature, as the thermoregulatory center in the brain sends a signal to the peripheral nervous system that resuts in vasodilation and heat dissipation.  As the body’s core divests more heat, and the gradient between chest and leg temperatures approaches zero degrees, sleep onset occurs.  We found in this study, however, that in children with FOH chest temperature remained high, sometimes throughout the entire sleep period, and leg temperature changed slowly relative to the comparison group.  Whereas, the skin temperature gradient reached zero degrees an average of 9 minutes after bedtime in the comparison children, it took longer than an hour for children the FOH group to reach this thermoregulatory balance.  Importantly, higher temperature gradients were significantly and strongly associated with the time it took to fall asleep.


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These initial findings provide robust, objective evidence for the link between temperature dysregulation, sleep/arousal issues, and emotion dysregulation that JBRF investigators theorize underlie the primary behavioral features of the disorder.  Our research continues to examine the role of thermoregulation in the biological basis of the FOH type of juvenile bipolar disorder.

Proposed Treatment 
As suggested by the physiological marker (skin temperature gradient) described above, we are exploring thermoregulatory approaches to treatment:

  • melatonin
  • fans
  • hypothermic agents
Next Steps 
JBRF has filed an IND application with the FDA to conduct a pharmaceutical study on an agent with hypothermic properties.  We plan to run a double blind placebo controlled study to determine the safety and efficacy of this agent in treating children with the FOH type of bipolar disorder.
 
The Sleep, Activity Patterns, and Temperature Study and its promising findings were made possible by JBRF, by the National Institutes of Health, and by you, our supportive community.  We are so grateful for your support and we are thrilled to present to you science based progress.

Your support of JBRF has made all of these advances possible. Your continued support will help produce the reliable and effective treatments that generations have dreamed of.   

Sincerely,

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Inger Sjogren

Executive Director

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