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Neuropsychopharmacology. 2011 Jan;36(1):183-206. doi: 10.1038/npp.2010.166. Epub 2010 Sep 22.

Frontocingulate dysfunction in depression: toward biomarkers of treatment response.

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  • 1Center for Depression, Anxiety, and Stress Research & Neuroimaging Center, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA.


Increased rostral anterior cingulate cortex (rACC) activity has emerged as a promising predictor of treatment response in depression, but neither the reliability of this relationship nor the mechanisms supporting it have been thoroughly investigated. This review takes a three-pronged approach to these issues. First, I present a meta-analysis demonstrating that the relationship between resting rACC activity and treatment response is robust. Second, I propose that the rACC plays a key role in treatment outcome because of its 'hub' position in the default network. Specifically, I hypothesize that elevated resting rACC activity confers better treatment outcomes by fostering adaptive self-referential processing and by helping to recalibrate relationships between the default network and a 'task-positive network' that comprises dorsolateral prefrontal and dorsal cingulate regions implicated in cognitive control. Third, I support this hypothesis by reviewing neuropsychological, electrophysiological, and neuroimaging data on frontocingulate dysfunction in depression. The review ends with a discussion of the limitations of current work and future directions.

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