The International Journal of Neuropsychopharmacology

Research Article

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

Lauren E. Cudneya1a2, Roberto B. Sassia1a3 *, Guilherme A. Behra2a4, David L. Streinera3a5, Luciano Minuzzia1a2a3, Jose C. F. Moreiraa4 and Benicio N. Freya1a2a3 c1 *

a1 Mood Disorders Program, St. Joseph's Healthcare Hamilton, ON, Canada

a2 Women's Health Concerns Clinic, St. Joseph's Healthcare Hamilton, ON, Canada

a3 Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada

a4 Centre of Oxidative Stress Research, Professor Tuiskon Dick Department of Biochemistry, Institute of Health Basic Sciences, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil

a5 Department of Psychiatry, University of Toronto, ON, Canada


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.

(Received August 07 2013)

(Reviewed August 26 2013)

(Revised December 10 2013)

(Accepted December 12 2013)

(Online publication January 17 2014)

Key words

  • Bipolar disorder;
  • circadian rhythms;
  • oxidative stress


c1 Address for correspondence: B. N. Frey, 301 James Street South, Suite F638, Hamilton, ON L8P 3B6, Canada. Tel.: +1 (905) 522-1155 Ext.# 33605 Fax: +1 (905) 521-6098 Email:


*  These authors contributed equally as senior authors.