Leo Sher, M.D.

Our research paper, “Positron emission tomography study of regional brain metabolic responses to a serotonergic challenge in major depressive disorder with and without comorbid lifetime alcohol dependence” was published 15 years ago in the September 2007 issue of European Neuropsychopharmacology (1). In this study, we compared the regional glucose metabolic rate (rCMRglu) responses to a serotonergic challenge in patients with major depressive disorder (MDD) with or without comorbid alcohol dependence.

Study participants received placebo on the first day and fenfluramine on the second in a single blind design. A bolus injection of approximately 5 mCi 18FDG was administered three hours after the administration of placebo/fenfluramine. A Siemens ECAT EXACT 47 scanner was used to acquire a 60-min emission scan in 2D mode as a series of twelve 5-min frames. Regions of significant differences in rCMRglu between depressed subjects with and without a history of alcoholism on placebo day and fenfluramine day were evaluated using Statistical Parametric Mapping.

When comparing rCMRglu after placebo administration in MDD patients with and without comorbid alcoholism, we found an anterior medial prefrontal cortical area where MDD patients with comorbid alcohol dependence had more severe hypofrontality than MDD patients without alcohol dependence. This area encompassed the left medial frontal and left and right anterior cingulate gyri. This group difference disappeared after fenfluramine administration. The fact that the observed group difference disappeared after the fenfluramine challenge suggests that serotonergic mechanisms play a role in the observed differences between the groups.

Reference

1. Sher L, Milak MS, Parsey RV, Carballo JJ, Cooper TB, Malone KM, Oquendo MA, Mann JJ. Positron emission tomography study of regional brain metabolic responses to a serotonergic challenge in major depressive disorder with and without comorbid lifetime alcohol dependence. Eur Neuropsychopharmacol. 2007 Sep;17(9):608-15.