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At present, both the neuropathophysiology of bipolar disorder as well as the mechanism(s) through which current mood-stabilizing agents provide symptom relief are unknown. Through the recent utilization of magnetic resonance spectroscopy (MRS), progress has been made; with optimistic interest being focused on the phosphatidylinositol (PI) cycle as a likely neuropathophysiological factor in bipolar disorder. The present manuscript reviews this interesting and promising area, placing emphasis on the magnetic resonance spectroscopy investigations of PI- cycle function in bipolar disorder reported to date. While relatively few well-designed MRS studies have investigated PI-cycle function in bipolar disorder, current evidence does lend support to PI-cycle involvement in bipolar neuropathophysiology as a means through which mood-stabilizing agents act; pointing to PI-cycle dysfunction as an important neuropathophysiological factor in bipolar disorder. However, there still remains a dearth of information about this interesting hypothesis. In addition to lithium, more data is needed regarding the effects on PI-cycle function of the other commonly prescribed mood-stabilizing agents. As well, studies investigating the temporal relationship between medication effect on PI-cycle functioning and symptom improvement are warranted. In tandem with clinical MRS investigation of bipolar disorder, further preclinical study of the neurochemical effects of mood-stabilizing agents is needed. Finally, greater methodological rigor needs to be implemented during the design phase of any future MRS investigation into bipolar disorder, with particular attention aimed at recruiting a large homogenous sample of bipolar patients.

Towards a Comprehensive Understanding of Bipolar Disorder: In Vivo MRS Investigation of the Phosphatidylinositol Cycle