Actigraphic assessment of circadian activity and sleep patterns in bipolar disorder

Abstract

Circadian activity disruption is apparent in bipolar patients even when not acutely ill. This finding is not associated with the presence of sleep disturbance. Should such patterns be replicated interventions to address both circadian instability and individual attributions for the effects of such instability are likely to be relevant to successful psychological interventions.

Assessment of circadian function in fibroblasts of patients with bipolar disorder

“…However, a decrease in overall levels of circadian gene expression; a trend toward reduced amplitude of circadian gene expression; and a decrease in GSK3b phosphorylation in fibroblasts derived from bipolar patients provide preliminary evidence for a link between the core circadian system and bipolar disorder. We propose that these anomalies, through downstream effects, may contribute to altered circadian rhythms as reported in bipolar patients 13,94,95 and may be involved in the etiology of the disorder.…”

“…[5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][80][81][82] However, molecular evidence for altered circadian clock in bipolar disorder is still lacking. It has been reported that similar components of the clock machinery underlie rhythmic gene expression in cultured fibroblasts as in the central clock in the SCN.…”

“…Altered overt circadian rhythms have been reported in bipolar patients, including blunted amplitudes of body temperature and plasma thyroid-stimulating hormone, 16,17,20,21 reduced urinary 3-methoxy-4-hydroxyphenylglycol amplitude, 12 blunted circadian amplitude of plasma tryptophan concentrations, 9 decreased serum melatonin, 14 abnormal activity level 13,19 and increased amplitude of cortisol. 10,11,15,18 We present molecular evidence for a reduction (either statistically significant or trending toward significance) in the amplitudes (for BMAL1, REV-ERBa and DBP) and in the overall levels (for DEC2 and DBP) of circadian gene expression in fibroblasts from bipolar patients.…”

“…89,[91][92][93] Although the observed reduction in the amplitude of circadian gene expression in BPI was subtle and only showed a trend for significance after correction for multiple comparisons, it is possible that the core clocks in bipolar patients are more vulnerable to external stimulation, which may contribute to unstable or more variable circadian rhythms as have been observed in bipolar patients. 13,94,95 Alterations in the overall expression level of core clock genes and clock-controlled genes can lead to anomalies in the circadian rhythmicity. For example, increased expression level of Per1 resulted in reduced amplitude of oscillations in the expression of Per2, RevErba and Bmal1.…”

“…In bipolar patients, alterations in phase, period and amplitude of circadian rhythms have been documented by measuring core temperature, hormonal secretion or actigraphy. [8][9][10][11][12][13][14][15][16][17][18][19][20][21] In addition, lithium, the most effective treatment for bipolar disorder 22,23 lengthens the circadian period in mammalian cells [24][25][26] and in model organisms. [27][28][29] Lithium treatment of 293T cells leads to rapid proteosomal degradation of REV-ERBa and transcriptional activation of BMAL1, 30 which are critical components of core clock mechanism.…”