Frontocingulate dysfunction in depression: toward biomarkers of treatment response

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


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.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antidepressive Agents / pharmacology
  • Antidepressive Agents / therapeutic use
  • Biomarkers, Pharmacological / chemistry
  • Biomarkers, Pharmacological / metabolism
  • Cognition / drug effects
  • Cognition / physiology
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / metabolism
  • Depressive Disorder, Major / physiopathology*
  • Gyrus Cinguli / chemistry*
  • Gyrus Cinguli / drug effects*
  • Gyrus Cinguli / physiology
  • Humans
  • Nerve Net / chemistry*
  • Nerve Net / drug effects*
  • Nerve Net / physiology
  • Outcome Assessment, Health Care / methods
  • Prefrontal Cortex / chemistry*
  • Prefrontal Cortex / drug effects*
  • Prefrontal Cortex / physiology


  • Antidepressive Agents
  • Biomarkers, Pharmacological