Leo Sher, M.D.

Our research report, “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 in the September 2007 issue of European Neuropsychopharmacology (1). It was the first study comparing the regional glucose metabolic rate (rCMRglu) responses to a serotonergic challenge in major depressive disorder with and without comorbid alcohol dependence.

A bolus injection of of (18)fluorodeoxyglucose was administered 3 hours after the administration of placebo or fenfluramine.  Fenfluramine causes a release of serotonin and regional brain metabolic responses to release of serotonin can be assessed by (18)fluorodeoxyglucose and positron emission tomography (2,3). Fenfluramine acts both presynaptically to increase serotonin release and postsynaptically as a receptor agonist.

We found an anterior medial prefrontal cortical area where subjects with comorbid major depressive disorder and alcohol dependence had more severe hypofrontality compared to patients with major depressive disorder without comorbid 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 fenfluramine administration indicates that serotonergic mechanisms play a role in the observed differences between the groups.

References

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.
2. Newman ME, Shapira B, Lerer B. Evaluation of central serotonergic function in affective and related disorders by the fenfluramine challenge test: a critical review. Int J Neuropsychopharmacol. 1998 Jul;1(1):49-69.
3. Sher L, Oquendo MA, Li S, Ellis S, Brodsky BS, Malone KM, Cooper TB, Mann JJ. Prolactin response to fenfluramine administration in patients with unipolar and bipolar depression and healthy controls. Psychoneuroendocrinology. 2003 May;28(4):559-73.