A proton magnetic resonance spectroscopy investigation of the dorsolateral prefrontal cortex in acute mania

BACKGROUND: Several neurochemical abnormalities have been reported in bipolar disorder (BD), but the exact mechanisms that underlie its pathophysiology remain to be elucidated. Proton magnetic resonance spectroscopy (1HMRS) allows in vivo measurements of certain neurometabolites in the human brain. 1HMRS was used to investigate the dorsolateral prefrontal cortex (DLPFC) in bipolar subjects during a manic or mixed phase. N-acetyl-L-aspartate (NAA), choline-containing molecules (Cho), creatine plus phosphocreatine (Cr) and myoinositol (Ino) were measured. METHOD: Ten bipolar patients (nine manic, one mixed), diagnosed by a semi-structured clinical interview (SCID), and ten age- and gender-matched healthy volunteers were studied. Absolute neurometabolites levels were measured from two 8 cm3 voxels placed in left and right DLPFC using a short TE 1HMRS method at 1.5 T. T1- and T2-weighted anatomical magnetic resonance imaging was performed to exclude any neuroanatomical abnormality. RESULTS: No significant differences were found for NAA, Cho, Cr, Ino, NAA/Cr, Cho/Cr or Ino/Cr between patients and controls. Manic/mixed patients had significantly higher left-to-right myoinositol ratios in DLPFC (p = 0.044). CONCLUSIONS: Increased left-to-right myoinositol ratios in the DLPFC in bipolar patients during acute mania may represent a dysfunction in the phosphoinositide-signaling pathway. Longitudinal studies with larger samples of unmedicated patients assessing pre- and post-treatment times will be required for further clarification of the time course of these abnormalities and the relationship with treatment effects.