title: Antidepressant medications reduce subcortical-cortical resting-state functional connectivity in healthy volunteers.
abstract: Studies have revealed abnormalities in resting-state functional connectivity in those with major depressive disorder specifically in areas such as the dorsal anterior cingulate, thalamus, amygdala, the pallidostriatum and subgenual cingulate. However, the effect of antidepressant medications on human brain function is less clear and the effect of these drugs on resting-state functional connectivity is unknown. Forty volunteers matched for age and gender with no previous psychiatric history received either citalopram (SSRI; selective serotonergic reuptake inhibitor), reboxetine (SNRI; selective noradrenergic reuptake inhibitor) or placebo for 7 days in a double-blind design. Using resting-state functional magnetic resonance imaging and seed based connectivity analysis we selected the right nucleus accumbens, the right amygdala, the subgenual cingulate and the dorsal medial prefrontal cortex as seed regions. Mood and subjective experience were also measured before and after drug administration using self-report scales. Despite no differences in mood across the three groups, we found reduced connectivity between the amygdala and the ventral medial prefrontal cortex in the citalopram group and the amygdala and the orbitofrontal cortex for the reboxetine group. We also found reduced striatal-orbitofrontal cortex connectivity in the reboxetine group. These data suggest that antidepressant medications can decrease resting-state functional connectivity independent of mood change and in areas known to mediate reward and emotional processing in the brain. We conclude that hypothesis-driven seed based analysis of resting-state fMRI supports the proposition that antidepressant medications might work by normalising the elevated resting-state functional connectivity seen in depressed patients.
authors.affiliation: Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, UK. ciara.mccabe@psych.ox.ac.uk
authors.forename: Ciara
authors.initials: C
authors.lastname: McCabe
authors.forename: Zevic
authors.initials: Z
authors.lastname: Mishor
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects*; D015283:Citalopram / Q000494:pharmacology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009434:Neural Pathways / Q000187:drug effects*; D000077593:Reboxetine; D012146:Rest / Q000502:physiology
chemical_list: D000928:Antidepressive Agents; D009025:Morpholines; D015283:Citalopram; D000077593:Reboxetine