Neural substrates of increased memory sensitivity for negative stimuli in major depression

Background: Although memory biases for negatively valenced stimuli have been reliably associated with depression and have been postulated to play a critical role in the maintenance of this disorder, the neural bases of these biases have received little attention. In this study, we tested a model of heightened memory sensitivity for negative information in depression in which neural mechanisms that normally facilitate memory for affective material are over-recruited during encoding of negative material in depression. Methods: We used functional magnetic resonance imaging to examine amygdala activity and functional connectivity with the hippocampus and caudate-putamen during successful encoding-as assessed by a recognition memory probe 1 week after scanning-of negative, neutral, and positive pictures by 14 depressed and 12 nondepressed individuals. Results: Depressed individuals demonstrated greater memory sensitivity than nondepressed participants to negative but not to neutral or positive stimuli. The right amygdala was more active and showed greater functional connectivity with the hippocampus and caudate-putamen in depressed than in control participants during encoding of subsequently remembered negative but not neutral or positive stimuli. The degree of memory-related right amygdala responsivity in the depressed participants was significantly correlated with depressive severity. Conclusions: These findings support the formulation that, in remembering negative information better than nondepressed persons, depressed individuals over-recruit a neural network involved more generally in enhancing memory for affective stimuli and that the degree to which they over-recruit this system is related to the severity of clinical symptomatology.