Description of the Condition

Physiological Marker for a Psychiatric Condition?

The findings of an NIMH funded study, Sleep, Activity Patterns, and Temperature Study conducted by JBRF researchers provides evidence for what may be the first physiological marker for a psychiatric syndrome. Why is this important to the JBRF community? Because it narrows the focus of our research to specific pathways in the brain, and may lead to novel treatment approaches.

Children who have the Fear of Harm type of bipolar disorder exhibit symptoms that reflect 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, carbohydrate craving/hoarding, disturbances in sleep onset and sleep offset, parasomnias (arousal disorders of sleep), as well overheating despite neutral ambient 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 dysregulated in children with FOH, and sleep quality is disturbed as a result. In this 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 results 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.

Researchers  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.

These initial findings provide 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. Follow-up studies of this research will continue 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, investigators are exploring thermoregulatory approaches to treatment: melatonin, fans to enhance heat dissipation during sleep, and hypothermic agents.

Next Steps

JBRF has filed an IND application which was approved by the FDA to conduct a pharmaceutical study in 6-12 year olds with an agent that has hypothermic properties, ketamine, and which in animal studies also has been found to reduce fear sensitization.  Researchers will conduct 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 evidenced-based research that is advancing knowledge in the field.