1. ¹Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA
2. ²Department of Radiology, Indiana University School of Medicine, Indianapolis, IN, USA
3. ³Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
4. ⁴Division of Radiology, The Cleveland Clinic Foundation, Cleveland, OH, USA

Correspondence: Dr A Anand, Outpatient Psychiatry Clinic, University Hospital Suite #3124, 550 N. University Boulevard, Indianapolis, IN 46202, USA. Tel: +1 317 274 7424; Fax: +1 317 274 1497; E-mail: aanand@iupui.edu

Received 27 July 2004; Revised 9 February 2005; Accepted 14 February 2005; Published online 27 April 2005.

Abstract

The mechanisms by which antidepressant-induced neurochemical changes lead to physiological changes in brain circuitry and ultimately an antidepressant response remain unclear. This study investigated the effects of sertraline, a selective serotonin reuptake inhibitor antidepressant, on corticolimbic connectivity, using functional magnetic resonance imaging (fMRI). In all, 12 unmedicated unipolar depressed patients and 11 closely matched healthy control subjects completed two fMRI scanning sessions at baseline and after 6 weeks. Depressed patients received treatment with sertraline between the two sessions. During each fMRI session, subjects first completed a conventional block-design experiment. Next, connectivity between cortical and limbic regions was measured using correlations of low-frequency blood oxygen level-dependent (BOLD) fluctuations (LFBF) during continuous exposure to neutral, positive, and negative pictures. At baseline, depressed patients had decreased corticolimbic LFBF correlations compared to healthy subjects during the resting state and on exposure to emotionally valenced pictures. At rest and on exposure to neutral and positive pictures, LFBF correlation between the anterior cingulate cortex and limbic regions was significantly increased in patients after treatment. However, on exposure to negative pictures, corticolimbic LFBF correlations remained decreased in depressed patients. The results of this study are consistent with the hypothesis that antidepressant treatment may increase corticolimbic connectivity, thereby possibly increasing the regulatory influence of cortical mood-regulating regions over limbic regions.