¹Brain Imaging Center, McLean Hospital, Belmont, MA, USA

Correspondence: C Stork, Brain Imaging Center, McLean Hospital, 115 Mill St, Belmont, MA 02478, USA. E-mail: cstork@mclean.harvard.edu

Received 2 May 2005; Revised 3 June 2005; Accepted 8 June 2005; Published online 12 July 2005.

Abstract

Magnetic resonance spectroscopy (MRS) affords a noninvasive window on in vivo brain chemistry and, as such, provides a unique opportunity to gain insight into the biochemical pathology of bipolar disorder. Studies utilizing proton (¹H) MRS have identified changes in cerebral concentrations of N-acetyl aspartate, glutamate/glutamine, choline-containing compounds, myo-inositol, and lactate in bipolar subjects compared to normal controls, while studies using phosphorus (³¹P) MRS have examined additional alterations in levels of phosphocreatine, phosphomonoesters, and intracellular pH. We hypothesize that the majority of MRS findings in bipolar subjects can be fit into a more cohesive bioenergetic and neurochemical model of bipolar illness that is both novel and yet in concordance with findings from complementary methodological approaches. In this review, we propose a hypothesis of mitochondrial dysfunction in bipolar disorder that involves impaired oxidative phosphorylation, a resultant shift toward glycolytic energy production, a decrease in total energy production and/or substrate availability, and altered phospholipid metabolism.