Functional Neuroimaging of Major Depressive Disorder: A Meta-Analysis and New Integration of Baseline Activation and Neural Response Data

Objective: Functional neuroimaging investigations of major depressive disorder can advance both the neural theory and treatment of this debilitating illness. Inconsistency of neuroimaging findings and the use of region-of-interest approaches have hindered the development of a comprehensive, empirically informed neural model of major depression. In this context, the authors sought to identify reliable anomalies in baseline neural activity and neural response to affective stimuli in major depressive disorder. Method: The authors applied voxel-wise, whole-brain meta-analysis to neuroimaging investigations comparing depressed to healthy comparison groups with respect to baseline neural activity or neural response to positively and/or negatively valenced stimuli. Results: Relative to healthy subjects, those with major depression had reliably higher baseline activity, bilaterally, in the pulvinar nucleus. The analysis of neural response studies using negative stimuli showed greater response in the amygdala, insula, and dorsal anterior cingulate cortex and lower response in the dorsal striatum and dorsolateral prefrontal cortex in individuals with major depressive disorder than in healthy subjects. Conclusions: The meta-analytic results support an elegant and neuroanatomically viable model of the salience of negative information in major depressive disorder. In this proposed model, high baseline pulvinar activity in depression first potentiates responding of the brain's salience network to negative information; next, and owing potentially to low striatal dopamine levels in depression, this viscerally charged information fails to propagate up the cortical-striatal-pallidal-thalamic circuit to the dorsolateral prefrontal cortex for contextual processing and reappraisal. (Am J Psychiatry 2012; 169:693-703)