• Mary L Phillips, Henry W Chase, Yvette I Sheline, Amit Etkin, Jorge R C Almeida, Thilo Deckersbach, and Madhukar H Trivedi.
• From the Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh; the Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia; the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford; the Department of Psychiatry, Massachusetts General Hospital, Boston; and the Department of Psychiatry, UT Southwestern Medical Center, Dallas.
• Am J Psychiatry. 2015 Feb 1; 172 (2): 124-38.

ObjectiveDespite significant advances in neuroscience and treatment development, no widely accepted biomarkers are available to inform diagnostics or identify preferred treatments for individuals with major depressive disorder.MethodIn this critical review, the authors examine the extent to which multimodal neuroimaging techniques can identify biomarkers reflecting key pathophysiologic processes in depression and whether such biomarkers may act as predictors, moderators, and mediators of treatment response that might facilitate development of personalized treatments based on a better understanding of these processes.ResultsThe authors first highlight the most consistent findings from neuroimaging studies using different techniques in depression, including structural and functional abnormalities in two parallel neural circuits: serotonergically modulated implicit emotion regulation circuitry, centered on the amygdala and different regions in the medial prefrontal cortex; and dopaminergically modulated reward neural circuitry, centered on the ventral striatum and medial prefrontal cortex. They then describe key findings from the relatively small number of studies indicating that specific measures of regional function and, to a lesser extent, structure in these neural circuits predict treatment response in depression.ConclusionsLimitations of existing studies include small sample sizes, use of only one neuroimaging modality, and a focus on identifying predictors rather than moderators and mediators of differential treatment response. By addressing these limitations and, most importantly, capitalizing on the benefits of multimodal neuroimaging, future studies can yield moderators and mediators of treatment response in depression to facilitate significant improvements in shorter- and longer-term clinical and functional outcomes.

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