The neural substrates of affective processing in depressed patients treated with venlafaxine.
OBJECTIVE
The purpose of this study was to use functional magnetic resonance imaging (fMRI) to probe the neural circuitry associated with reactivity to negative and positive affective stimuli in patients with major depressive disorder before treatment and after 2 and 8 weeks of treatment with venlafaxine. Relations between baseline neural activation and response to treatment were also evaluated.


METHODS
Patients with major depressive disorder (N=12) and healthy comparison subjects (N=5) were scanned on three occasions, during which trials of alternating blocks of affective and neutral pictorial visual stimuli were presented. Symptoms were evaluated at each testing occasion, and both groups completed self-report measures of mood. Statistical parametric mapping was used to examine the fMRI data with a focus on the group-by-time interactions.


RESULTS
Patients showed a significant reduction in depressive symptoms with treatment. Group-by-time interactions in response to the negative versus neutral stimuli were found in the left insular cortex and the left anterior cingulate. At baseline, both groups showed bilateral activation in the visual cortices, lateral prefrontal cortex, and amygdala in response to the negative versus neutral stimuli, with patients showing greater activation in the visual cortex and less activation in the left lateral prefrontal cortex. Patients with greater relative anterior cingulate activation at baseline in response to the negative versus neutral stimuli showed the most robust treatment response.


CONCLUSIONS
The findings underscore the importance of the neural circuitry activated by negative affect in depression and indicate that components of this circuitry can be changed within 2 weeks of treatment with antidepressant medication.
Davidson
Richard J
RJ
Department of Psychology, University of Wisconsin, 1202 West Johnson St., Madison, WI 53706, USA. rjdavids@facstaff.wisc.edu
Irwin
William
W
Anderle
Michael J
MJ
Kalin
Ned H
NH
D000328:Adult; D000339:Affect / Q000187:drug effects* / Q000502:physiology; D000679:Amygdala / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D003511:Cyclohexanols / Q000009:adverse effects / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006179:Gyrus Cinguli / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000187:drug effects* / Q000503:physiopathology; D016896:Treatment Outcome; D000069470:Venlafaxine Hydrochloride
D003511:Cyclohexanols; D000069470:Venlafaxine Hydrochloride