Our study shows a dose-dependent association between the severity of depressive symptoms and degree of biological rhythms disturbance. Biological rhythms disturbance was also an independent predictor of functional impairment. Although the directionality of this relationship remains unknown, our results suggest that stability of biological rhythms should be an important target of acute and long-term management of bipolar disorder and may aid in the improvement of functioning.

Disturbances in both circadian rhythms and oxidative stress systems have been implicated in the pathophysiology of bipolar disorder (BD), yet no studies have investigated the relationship between these systems in BD. We studied the impact of circadian rhythm disruption on lipid damage in 52 depressed or euthymic BD females, while controlling for age, severity of depressive symptoms and number of psychotropic medications, compared to 30 healthy controls. Circadian rhythm disruption was determined by a self-report measure (Biological Rhythm Interview of Assessment in Neuropsychiatry; BRIAN), which measures behaviours such as sleep, eating patterns, social rhythms and general activity. Malondialdehyde (MDA) levels were measured as a proxy of lipid peroxidation. We also measured the activity of total and extracellular superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST). Multiple linear regressions showed that circadian rhythm disturbance was independently associated with increased lipid peroxidation in females with BD (p < 0.05). We found decreased extracellular SOD (p < 0.05), but no differences in total SOD, CAT or GST activity between bipolar females and controls. Circadian rhythms were not associated with lipid peroxidation in healthy controls, where aging was the only significant predictor. These results suggest an interaction between the circadian system and redox metabolism, in that greater disruption in daily rhythms was associated with increased lipid peroxidation in BD only. Antioxidant enzymes have been shown to follow a circadian pattern of expression, and it is possible that disturbance of sleep and daily rhythms experienced in BD may result in decreased antioxidant defence and therefore increased lipid peroxidation. This study provides a basis for further investigation of the links between oxidative stress and circadian rhythms in the neurobiology of BD.

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BackgroundEvidence suggests that patients with bipolar disorder (BD) experience biological rhythm disturbances; however, no studies have examined the impact of this disruption on quality of life (QOL). The aim of this study is to investigate the influence of biological rhythm, depressive symptoms, sleep quality, and sleep medication use on QOL in BD.MethodsEighty BD subjects (44 depressed and 36 euthymic) completed questionnaires assessing QOL (WHOQOL-BREF), biological rhythm disruption (BRIAN), depressive symptoms (MADRS), and sleep quality (PSQI). The impact of biological rhythm disturbance, depressive symptoms severity, sleep quality, and sleep medication use on QOL was determined with multiple regression analyses.ResultsBRIAN (β = −0.31, t = −2.73, p < 0.01), MADRS (β = −0.30, t = −2.93, p < 0.01), and sleep medication use (β = −0.45, t = −2.55, p < 0.05) were significant predictors of QOL in this model (F4, 75 = 20.28; p < 0.0001). The relationship of these factors with subdomains of QOL showed that poorer social QOL was associated with greater biological rhythm disturbance (β = −0.43, t = −3.66, p < 0.01) and sleep medication use (β = −0.49, t = −2.35, p < 0.01), providing support for the social rhythm theory of BD. Physical QOL was associated with depression (β = −0.30, t = −2.93, p < 0.01) and biological rhythm disruption (β = −0.31, t = −2.73, p < 0.01). Main limitations include the cross-sectional assessment and the lack of objective measures of biological rhythms in relation to QOL.ConclusionsDisruption in biological rhythm is associated with poor QOL in BD, independent of sleep disturbance, sleep medication use, and severity of depression. Treatment strategies targeting regulation of biological rhythms, such as sleep/wake cycles, eating patterns, activities, and social rhythms, are likely to improve QOL in this population.