Response to SSRI intervention and amygdala activity during self-referential processing in major depressive disorder.

There are conflicting reports on the impact of antidepressants on neural reactions for positive information. We thus hypothesized that there would be clinically important individual differences in neural reactivity to positive information during SSRI therapy. We further predicted that only those who responded to SSRIs would show increased amygdala reactivity to positive information following treatment to a level similar to that seen in healthy participants. Depressed individuals (n = 17) underwent fMRI during performance of a task involving rating the self-relevance of emotionally positive and negative cue words before and after receiving 12 weeks of SSRI therapy. At post-treatment, SSRI responders (n = 11) had increased amygdala activity in response to positive stimuli, and decreased activity in response to negative stimuli, compared to non-responders (n = 6). Results suggest that normalizing amygdala responses to salient information is a correlate of SSRI efficacy. Second line interventions that modulate amygdala activity, such as fMRI neurofeedback, may be beneficial in those who do not respond to SSRI medications.

Toward clinically useful neuroimaging in depression treatment: prognostic utility of subgenual cingulate activity for determining depression outcome in cognitive therapy across studies, scanners, and patient characteristics.

CONTEXT Among depressed individuals not receiving medication in controlled trials, 40% to 60% respond to cognitive therapy (CT). Multiple previous studies suggest that activity in the subgenual anterior cingulate cortex (sgACC; Brodmann area 25) predicts outcome in CT for depression, but these results have not been prospectively replicated. OBJECTIVE To examine whether sgACC activity is a reliable and robust prognostic outcome marker of CT for depression and whether sgACC activity changes in treatment. DESIGN Two inception cohorts underwent assessment with functional magnetic resonance imaging using different scanners on a task sensitive to sustained emotional information processing before and after 16 to 20 sessions of CT, along with a sample of control participants who underwent testing at comparable intervals. SETTING A hospital outpatient clinic. PATIENTS Forty-nine unmedicated depressed adults and 35 healthy controls. MAIN OUTCOME MEASURES Pretreatment sgACC activity in an a priori region in response to negative words was correlated with residual severity and used to classify response and remission. RESULTS As expected, in both samples, participants with the lowest pretreatment sustained sgACC reactivity in response to negative words displayed the most improvement after CT (R2 = 0.29, >75% correct classification of response, >70% correct classification of remission). Other a priori regions explained additional variance. Response/remission in cohort 2 was predicted based on thresholds from cohort 1. Subgenual anterior cingulate activity remained low for patients in remission after treatment. CONCLUSIONS Neuroimaging provides a quick, valid, and clinically applicable way of assessing neural systems associated with treatment response/remission. Subgenual anterior cingulate activity, in particular, may reflect processes that interfere with treatment (eg, emotion generation) in addition to its putative regulatory role; alternately, its absence may facilitate treatment response.