Brain metabolic changes in major depressive disorder from pre- to post-treatment with paroxetine

Functional brain imaging studies of subjects with Major Depressive Disorder (MDD) have suggested that decreased dorsolateral (DLPFC) and increased ven trolateral (VLPFC) prefrontal cortical activity mediate the depressed state . Pre- to post-treatment studies indicate that these abnormalities normaliz e with successful treatment. We performed [F-18]fluorodeoxyglucose positron emission tomography (FDG-PET) scans on 16 outpatients with MDD before and after treatment with paroxetine (target dose = 40 mg/day). Regions of inter est (ROIs) for this analysis were drawn by a rater blind to subject identit y on the magnetic resonance image of each subject and transferred onto thei r coregistered PET scans. We hypothesized that DLPFC metabolism would incre ase, while ventral frontal metabolism [in the VLPFC, the orbitofrontal cort ex (OFC), and the inferior frontal,gyrus (IFG)] would decrease with success ful treatment. Treatment response was defined as a decrease in the Hamilton Depression Rating Scare of > 50% and a Clinical Global Improvement Scale r ating of 'much' or 'very much' improved. By these criteria, nine of the sub jects were classified as treatment responders. These responders had signifi cantly greater decreases in normalized VLPFC and OFC metabolism than did no n-responders. There were no significant effects of treatment response on ch ange in the DLPFC or IFG in this sample. However, there was a positive corr elation between change in HAM-D scores and change in normalized IFG and VLP FC metabolism. There were no significant interactions with laterality. On p re-treatment scans, lower metabolism in the left ventral anterior cingulate gyrus was associated with better treatment response. These findings implic ate ventral prefrontal-subcortical brain circuitry in the mediation of resp onse to serotonin reuptake inhibitors in MDD. (C) 1999 Elsevier Science Ire land Ltd. All rights reserved.