Mitochondrial DNA variation and increased oxidative damage in euthymic patients with bipolar disorder

Abstract

The aim of this study was to compare alterations of mitochondrial DNA (mtDNA) copy number, single nucleotide polymorphisms, and oxidative damage of mtDNA in clinically stable patients with bipolar I disorder (BD). Patients meeting DSM-IV diagnostic criteria for BD were recruited from the psychiatric outpatient clinic at Changhua Christian Hospital, Taiwan. They were clinically stable and their medications had not changed for at least the preceding 2 months. Exclusion criteria were substance-induced psychotic disorder, eating disorder, anxiety disorder or illicit substance abuse. Comparison subjects did not have any history of major psychiatric disorders and they were non-smokers. By analyzing peripheral blood leukocytes, copy number, single nucleotide polymorphisms and oxidative damage of mtDNA were compared between the two groups. The median age of the subjects was 38 years and 41.5 years in the comparison and BD groups, respectively. The leukocyte mtDNA copy number of the BD group was significantly lower than that of the comparison group (P < 0.001). BD patients had significantly higher mitochondrial oxidative damage than the comparison group (6.1 vs 3.9, P < 0.001). After generalized linear model adjusting with age, sex, smoking, family history, and psychotropic use, mtDNA copy number was still significantly lower in the BD group (P < 0.001). MtDNA oxidative damage was positively correlated with age (P = 0.034), although mtDNA oxidative damage was similar between these two groups. Possible involvement of oxidative stress and mitochondria in the pathophysiology of BD needs more large-scale studies. It is important that psychiatrists retain a high level of suspicion for mitochondrial dysfunction in patients with bipolar disorder.