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Reciprocal Effects of Antidepressant Treatment on Activity and Connectivity of the Mood Regulating Circuit: An fMRI Study

Received April 28, 2006; revised June 19, 2006; accepted July 4, 2006. Drs. Anand and Li and Ms. Gardner are affiliated with the Department of Psychiatry, Indiana University School of Medicine, Indianapolis, Indiana. Drs. Anand and Wang are affiliated with the Department of Radiology, Indiana University School of Medicine, Indianapolis, Indiana. Dr. Lowe is affiliated with the Division of Radiology, the Cleveland Clinic Foundation, Indianapolis, Indiana. Address correspondence to Dr. Anand, Outpatient Psychiatry Clinic, University Hospital Suite #3124, 550 North University Boulevard, Indianapolis, IN 46202; aanand{at}iupui.edu (e-mail).

It has been hypothesized that one of the effects of antidepressants is to increase functional connectivity between the cortical mood-regulating and the limbic mood-generating regions. One consequence of this antidepressant effect is thought to be decreased limbic activation in response to negative emotional stimuli. Twelve unmedicated unipolar depressed patients and 11 closely matched healthy comparison subjects completed two magnetic resonance imaging (MRI) scanning sessions at baseline and after 6 weeks. Depressed patients received treatment with sertraline between the two sessions. During each MRI session, subjects completed a resting state functional connectivity scan and a conventional block-design negative vs. neutral pictures regional brain activation scan. After 6 weeks of sertraline treatment resting state, functional connectivity between the ACC and limbic regions increased while limbic activation in response to negative versus neutral pictures decreased. The results of this study are consistent with the hypothesis that antidepressant treatment has reciprocal effects on corticolimbic functional connectivity and limbic activation in response to emotional stimuli.

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