Subgenual cingulate and visual cortex responses to sad faces predict clinical outcome during antidepressant treatment for depression

Background: Previous follow-up studies indicate that increased visual cortical, ventral cingulate and subcortical responses of depressed individuals to sad facial stimuli, but not happy stimuli could represent reversible markers of disease severity. We hypothesized that greater responses in these areas to sad stimuli, but not happy stimuli, would predict better subsequent clinical outcome. We also explored areas that would predict a poor outcome. Methods: Twelve melancholically depressed individuals in the early stages of antidepressant treatment in a secondary care setting participated in two experiments comparing responses to varying intensities of sad and happy facial stimuli, respectively, using event related functional MRI. They repeated the experiments after a mean delay of 12 weeks of treatment. Results: There was a variation in response to treatment. Greater right visual cortex and right subgenual cingulate (R-BA25) responses to sad stimuli, but not happy stimuli, in the early stages of treatment were associated with a good clinical outcome. Greater ventrolateral prefrontal cortex responses to either stimulus type were associated with a relatively poor outcome. Limitations: The sample size was modest and patients were taking a variety of antidepressants. Conclusions: Right subgenual cingulate and right visual cortical responses to sad stimuli predict good clinical outcome in the context of antidepressant treatment for severe depression in a naturalistic setting. Ventrolateral prefrontal cortex activity may indicate poor prognosis due to its relationship with negative rumination. (C) 2009 Elsevier B.V. All rights reserved.