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Circadian Rhythms and Clock Genes in Inter-episode Bipolar Disorder

Abstract

Objectives: Circadian rhythms are hypothesized to be disturbed in bipolar disorder (BD). However, the empirical evidence for this hypothesis is mixed. Hence, the goals of the current investigation were to extend and contribute to clarifying the literature on circadian rhythms in inter-episode BD by comparing proxies for circadian rhythm functioning in BD I and II individuals, relative to healthy controls.

Methods: Thirty-five adults diagnosed with inter-episode BD I and II were compared to 37 healthy controls of similar age and gender. All participants completed a questionnaire assessing chronotype, reported daily sleep and wake times for four weeks, and wore wrist actigraphy for four weeks in order to assess objective estimates of sleep and wake timing and to calculate the cosinor variables, MESOR, amplitude and acrophase, as proxies for circadian modulation of activity. Participants also provided a saliva sample in order to analyze DNA for polymorphisms of the clock genes PER3 and CLOCK.

Results: There were no significant differences between the BD and control groups on questionnaire reported chronotype, although there was a trend for significance such that BD individuals were more likely to report an evening chronotype. BD individuals exhibited more instability in sleep and wake timing as assessed by both sleep diary and actigraphy. There were no significant differences between the BD and control groups on any of the cosinor analysis variables; namely, MESOR, amplitude and acrophase. There was a trend for differences in MESOR among BD individuals who were carriers of the C-allele of the CLOCK gene. There were no differences in circadian cosinor variables for any of the genotype groups of PER3.

Conclusions: The current findings are not consistent with previous hypotheses that abnormal circadian activity rhythms are enduring (trait) characteristics of BD individuals. However, instability in sleep timing may be characteristic of the inter-episode period.

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