Association of bipolar disorder with the 5178 polymorphism in mitochondrial DNA

Parent-of-origin effect in transmission of bipolar disorder and abnormal ph osphorus-31 magnetic resonance spectroscopy (P-31-MRS) findings in the brai n in patients with bipolar disorder implicate pathophysiological role of mi tochondrial DNA in bipolar disorder. The authors examined possible associat ion of bipolar disorder with the 5178 polymorphism in mitochondrial DNA. Ge notype frequencies of the 5178 polymorphism were examined by polymerase cha in reaction-restriction fragment length polymorphism method in 145 patients with bipolar disorder and 184 controls. The rate of 5178C genotype was sig nificantly higher in patients with bipolar disorder (81/125 (64.8%), P < 0. 05) compared with controls (98/184 (53.2%)) when paternally transmitted cas es were excluded. This effect was more prominent in patients with bipolar I I disorder (5178C: 28/37, 75.6%, P < 0.02 to controls). Bipolar II patients with 5178A genotype without family history had significantly later age at onset (56.0 +/- 14.7 years, P < 0.05) than other bipolar patients. Brain in tracellular pH measured by P-31-MRS was significantly higher in bipolar pat ients with 5178A (7.04 +/- 0.03, n = 7, P < 0.05) than those with 5178C (7. 00 +/- 0.03, n = 7), There was no difference of subcortical hyperintensity scores by magnetic resonance imaging between patients with 5178A and those with 5178C, These results suggest that the 5178 polymorphism in mitochondri al DNA may regulate vulnerability to bipolar disorder via alteration of bra in energy metabolism, (C) 2000 Wiley-Liss, Inc.