Bruce P Doré1, Odile Rodrik2, Chelsea Boccagno2, Alexa Hubbard3, Jochen Weber2, Barbara Stanley4, Maria A Oquendo5, Jeffrey M Miller4, M Elizabeth Sublette4, J John Mann6, Kevin N Ochsner2. 1. Annenberg School for Communication, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: brucedore@gmail.com. 2. Department of Psychology, Columbia University, New York, New York. 3. Department of Psychology, New York University, New York, New York. 4. Department of Psychiatry, Columbia University, New York, New York; Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, New York. 5. Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. 6. Department of Psychiatry, Columbia University, New York, New York; Department of Neurology, Columbia University, New York, New York; Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, New York.
Abstract
BACKGROUND: Dysregulated autobiographical recall is observed in major depressive disorder (MDD). However, it is unknown whether people with MDD show abnormalities in memory-, emotion-, and control-related brain systems during reactivity to and regulation of negative autobiographical memories. METHODS: We used functional magnetic resonance imaging to identify neural mechanisms underlying MDD-related emotional responses to negative autobiographical memories and the ability to downregulate these responses using a cognitive regulatory strategy known as reappraisal. We compared currently depressed, medication-free patients with MDD (n = 29) with control participants with no history of depression (n = 23). RESULTS: Relative to healthy control participants, medication-free MDD patients reported greater negative emotion during recall but relatively intact downregulation success. They also showed elevated amygdala activity and greater amygdala-hippocampal connectivity. This connectivity mediated the effect of MDD on negative emotional experience. When reappraising memories (vs. recalling from an immersed perspective), the MDD and control groups showed comparable recruitment of the prefrontal, parietal, and temporal cortices, and comparable downregulation of the amygdala and anterior hippocampus. However, MDD patients showed greater downregulation of the posterior hippocampus, and the extent of this downregulation predicted successful reduction of negative affect in MDD patients only. CONCLUSIONS: These data suggest amygdala-hippocampal connectivity and posterior hippocampal downregulation as brain mechanisms related to elevated emotional reactivity and atypical emotion regulation in MDD.
BACKGROUND: Dysregulated autobiographical recall is observed in major depressive disorder (MDD). However, it is unknown whether people with MDD show abnormalities in memory-, emotion-, and control-related brain systems during reactivity to and regulation of negative autobiographical memories. METHODS: We used functional magnetic resonance imaging to identify neural mechanisms underlying MDD-related emotional responses to negative autobiographical memories and the ability to downregulate these responses using a cognitive regulatory strategy known as reappraisal. We compared currently depressed, medication-free patients with MDD (n = 29) with control participants with no history of depression (n = 23). RESULTS: Relative to healthy control participants, medication-free MDDpatients reported greater negative emotion during recall but relatively intact downregulation success. They also showed elevated amygdala activity and greater amygdala-hippocampal connectivity. This connectivity mediated the effect of MDD on negative emotional experience. When reappraising memories (vs. recalling from an immersed perspective), the MDD and control groups showed comparable recruitment of the prefrontal, parietal, and temporal cortices, and comparable downregulation of the amygdala and anterior hippocampus. However, MDDpatients showed greater downregulation of the posterior hippocampus, and the extent of this downregulation predicted successful reduction of negative affect in MDDpatients only. CONCLUSIONS: These data suggest amygdala-hippocampal connectivity and posterior hippocampal downregulation as brain mechanisms related to elevated emotional reactivity and atypical emotion regulation in MDD.
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