Alterations in circadian rhythms are associated with increased lipid peroxidation in females with bipolar disorder

• Published in: The international journal of neuropsychopharmacology Vol. 17; no. 5; pp. 715 - 722
• Main Authors: Cudney, Lauren E., Sassi, Roberto B., Behr, Guilherme A., Streiner, David L., Minuzzi, Luciano, Moreira, Jose C. F., Frey, Benicio N.
• Format: Journal Article
• Language: English
• Published: Cambridge, UK Cambridge University Press 01.05.2014; Oxford University Press
• Subjects: Adult; Aging; Bipolar Disorder - complications; Bipolar Disorder - drug therapy; Bipolar Disorder - metabolism; Blood Gas Analysis; Catalase - blood; Chronobiology Disorders - complications; Chronobiology Disorders - metabolism; Female; Glutathione Transferase - blood; Humans; Linear Models; Lipid Peroxidation; Malondialdehyde - blood; Psychotropic Drugs - therapeutic use; Self Report; Superoxide Dismutase - blood; circadian rhythms; Bipolar disorder; oxidative stress
• ISSN: 1461-1457; 1469-5111
• DOI: 10.1017/S1461145713001740

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.