Antidepressant Effect on Connectivity of the Mood-Regulating Circuit: An fMRI Study

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 lowfrequency 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.

Resting-State Functional Connectivity in Major Depression: Abnormally Increased Contributions from Subgenual Cingulate Cortex and Thalamus

“…Most germane to our findings, a recent region-of-interest (ROI), resting-state connectivity analysis has shown reduced connectivity between the medial thalamus and the dorsal, putatively cognitive, aspect of the anterior cingulate in depressed subjects compared to controls (Anand et al 2005a). In the same group of subjects, resting-state connectivity between the medial thalamus and dorsal anterior cingulate normalized following treatment with sertraline (Anand et al 2005b). In light of these findings, we are encouraged by the detection here of increased thalamic functional connectivity in the default-mode network of depressed subjects.…”

Alterations of fronto-temporal connectivity during word encoding in schizophrenia

“…Nonetheless, timeseries correlation analysis has been utilized in studies of normal cognitive and emotional states (Greicius et al, 2003;Bartels and Zeki, 2005;Fox et al, 2005;Menon and Levitin, 2005), disease states (Lowe et al, 2002;Anand et al, 2005;Koshino et al, 2005;), and pharmacological interventions (Li et al, 2000;Honey et al, 2003;Peltier et al, 2005). Our study contributes to a rapidly growing body of knowledge regarding normal and abnormal functional neural circuitry.…”

“…Several specific approaches have been implemented (Horwitz, 2003), and their relative merits have not been established. The timeseries correlation method (Biswal et al, 1995;Lowe et al, 1998) examines interregional correlations within individual subjects over the timecourse of an experiment, and has been effectively applied to measure functional connectivity across a wide range of cognitive and physiological states (Li et al, 2000;Lowe et al, 2002;Greicius et al, 2003;Honey et al, 2003;Anand et al, 2005;Bartels and Zeki, 2005;Fox et al, 2005;Koshino et al, 2005;Menon and Levitin, 2005;Peltier et al, 2005).…”

Effects of methylphenidate on resting-state brain activity in normal adults: an fMRI study

“…Konrad et al also summarized the structural connectivity of participants with ADHD [39] . In unmedicated unipolar depressed patients, after 6 weeks of treatment with sertraline, the low-frequency blood oxygen level-dependent fluctuations correlation between the anterior cingulate cortex and limbic regions is significantly increased when participants are at rest [40] .…”