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 (R-2 = 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.