Familial risk for bipolar disorder is not associated with impaired peroxisomal function: Dissociation from docosahexaenoic acid deficits.

Bipolar I disorder is associated with deficits in the long-chain omega-3 fatty acid docosahexaenoic acid (DHA, 22:6n-3). The final biosynthesis of DHA is mediated by peroxisomes, and some heritable peroxisomal disorders are associated with DHA deficits and progressive psychopathology. The present cross-sectional study investigated whether medication-free asymptomatic and symptomatic youth with familial risk for bipolar I disorder exhibit impaired peroxisomal function using a comprehensive diagnostic blood panel. Measures of peroxisomal impairment included plasma concentrations of very long-chain fatty acids (VLCFA), branched-chain fatty acids, bile acid intermediates, and pipecolic acid, and erythrocyte plasmalogen and DHA levels. Compared with healthy subjects, significant erythrocyte DHA deficits were observed in ultra-high risk and first-episode bipolar groups, and there was a trend for lower DHA in the high-risk group. There were no significant group differences for any other measure of peroxisomal function, and erythrocyte DHA levels were not correlated with any measure of peroxisome function. These results indicate that familial risk for bipolar I disorder is not associated with impaired peroxisomal function, and that DHA deficits associated with familial bipolar disorder are not attributed to heritable defects in peroxisomal function.