Circadian Rhythm - Sleep/Wake Study in Juvenile-onset Bipolar Disorder

Circadian Sleep/Wake, Body Temperature Rhythm
Study in Childhood-onset Bipolar Disorder

Demitri F. Papolos, M.D. Department of Psychiatry, Albert Einstein College of Medicine
Margaret Moline, Ph.D. Department of Psychiatry, New York - Presbyterian Hospital (Westchester Division) and Weill Medical College of New York University

The primary objective of this study is to examine clinical and circadian characteristics, such as the presence of ultra-ultra rapid cycling pattern of activity and mood, desynchrony of circadian activity, core body temperature, melatonin and cortisol rhythms, and the presence of REM and NREM parasomnias, in a group of patients (ages 6-12) diagnosed with childhood-onset bipolar disorder (COBPD) in comparison to a sex and age-matched control group.

Great variability is evident in the frequency of episode recurrence and duration in patients with bipolar disorder. In addition to regular circannual episodes, a spectrum of cycle frequencies has been observed, from the classical adult rapid cycling pattern of four or more episodes per year, to those with distinct shifts of mood and activity occurring within a 24-48 hour period, described as ultra-ultra rapid cycling (UURC) or ultradian cycling. Recently, researchers have found the rates of ultra-ultra rapid cycling in childhood-onset bipolar disorder to range between 50-80%. In the largest sample to date (N=120), Papolos and Papolos (1999) reported that 85% experienced multiple cycles of mood and activity within the day. 75% of this group displayed a characteristic activity pattern, typified by low levels of activity and energy in the morning with depressed mood, followed by marked motor restlessness, agitation and activation after in the late afternoon, early evening; with a second higher peak of activity in the late evening, as well as sleep arousal disorders, including night-terrors, multiple sleep awakenings, and sleep-walking.

Taken together, these studies suggest that juvenile-onset bipolar disorder presents in the large majority of cases with an ultra-ultra rapid cycling pattern, and is associated with a prominent diurnal pattern of activity, as well as sleep arousal disorders suggestive of a disturbance of the REM-NREM sleep cycle.

The study will examine, for the first time, circadian measures of core body temperature, activity, and REM propensity rhythm, as well as salivary melatonin and cortisol levels, in a group of juvenile-onset bipolar patients in comparison with normal controls.

30 patients (ages 6-12) meeting DSM-IV criteria (modified to include ultra-ultra rapid or ultradian cycling variant) for acute manic episodes will be compared with a group of 30 control subjects. Diagnoses will be established from a dataset that will include a comprehensive battery of questionnaires and the KSADS P/L interview given to research subjects and their mothers.

Expert diagnosticians (child psychiatrists, research psychologists) will participate in the diagnostic assessment arm of the study through the Expert Diagnostic Workshop:
http://www.jbrf.org/grand/index.cfm.

Circadian rhythm/sleep studies will be performed at the Sleep-Wake Disorders Center of New York Presbyterian Hospital, Westchester Division, under the direction of Dr. Margaret Moline, director of the center, and a co-principal investigator on the project.

• If a subject meets preliminary entry criteria for participation in this study, he/she will undergo electrocardiogram, chemistry profile, thyroid stimulating hormone level, CBC with differential and platelets, and urinalysis. A physical examination including vital signs (blood pressure, pulse, height, and weight) will be obtained.
• Parents will be asked to complete several behavioral screening tools: Child Bipolar Questionnaire (CBQ), Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), the Overt Aggression Scale (OAS), and the Child Behavioral Check List.
• The SADS P/L will be administered to establish DSM-IV diagnoses. Symptom severity will be measured by using the Young Mania scale, the Global Assessment Scale (GAS), and the Brief Psychiatric Rating Scale (BPRS) at study onset.
• On entry into the study, patient-subjects will wear activity monitors for 5 days before the laboratory studies. Parents will complete sleep logs on behalf of their children to aid in data analysis of the actigraphy data, which will be used as an objective measure of circadian and ultradian patterns in activity. After the 5 days of actigraphy, patients will spend two nights in the Sleep Studies Unit at New York-Presbyterian Hospital (Westchester Division). 24-hour body temperature (measured non-invasively in the armpit), activity, salivary cortisol, and salivary melatonin will be obtained. In addition, sleep-EEG and videotaping to assess for the presence of parasomnias (REM and NREM) will be performed. Wrist actigraphy will continue so that a full week of data are collected.

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