Neurochemical alteration in the caudate: implications for the pathophysiology of bipolar disorder

Several lines of evidence suggest that the neuropathophysiology of bipolar disorder is marked by structural and functional abnormalities in the caudate. We used magnetic resonance spectroscopy imaging (MRSI) to examine potential neurochemical changes in the caudate of adult bipolar patients (BP). 2D-MRSI scans including the caudate were obtained from 25 BP and 9 healthy subjects (HS). BP patients were further divided into medicated (n=14) and unmedicated (n=11) groups; the majority of medicated patients received atypical antipsychotics (AAP). Ratios of Cr/Cho, Cho/NAA and Cr/NAA in the caudate were compared between groups, controlling for age, gender and gray/white ratio. BP and HS did not significantly differ on any ratios. The Cr/Cho ratio, however, was significantly greater in medicated BP compared to HS. Conversely, the Cho/NAA ratio was non-significantly lower in medicated BP vs. HS. Medicated BP also showed significantly greater Cr/Cho and significantly smaller Cho/NAA ratios than unmedicated BP. Although we did not observe significant overall differences between BP and HS, our findings suggest the presence of reduced choline levels in the caudate of medicated BP receiving AAP. While speculative, these results suggest that AAP do not cause oxidative injury to neuronal membranes.