Juvenile Bipolar Research Foundation, Inc.

This is a study designed to provide preliminary data on the therapeutic effects of intranasal ketamine in subjects with a recently reported phenotype of pediatric bipolar disorder that has been titled the ‘Fear of Harm’ (FOH) phenotype. FOH is associated with separation anxiety, aggressive obsessions, and behavioral symptoms that mimic those of post-traumatic stress disorder. Children with FOH often experience thermal discomfort (e.g., feeling hot, excessive sweating) in neutral ambient temperature conditions, as well as no discomfort during exposure to the extreme cold, and alternate noticeably between being excessively hot in the evening and cold in the morning. This putative, heritable phenomenon (a deficit in thermoregulation) - a tendency to generate excessive heat and/or a deficit in heat dissipation results in REM sleep-related problems and parasomnias (night- terrors, sleep-walking, sleep-talking, bruxism, and enuresis), as well as morning sleep inertia. Clinically, FOH is associated with the advent in early childhood of recurrent, vivid, nightmares with themes of pursuit and abandonment. The apparent psychological sequelae of exposure to this frequent, frightening imagery is fear sensitization. A developmental sequence of fear based defensive behaviors arises and includes obsessive bedtime rituals, fear of the dark, separation anxiety, contamination fears, hypervigilance, misperception of neutral stimuli as threatening, reactive aggression in response to limit setting and perceived threat or loss.