Shefali Miller1,2, Lisa M McTeague1,2, Anett Gyurak1,2,3, Brian Patenaude1,2, Leanne M Williams1,2, Stuart M Grieve4,5,6, Mayuresh S Korgaonkar4,7, Amit Etkin1,2. 1. Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California. 2. Sierra-Pacific Mental Illness Research, Education, and Clinical Center (MIRECC), Veterans Affairs Palo Alto Health Care System, Palo Alto, California. 3. Department of Psychology, Stanford University, Stanford, California. 4. Brain Dynamics Center, Sydney Medical School, The University of Sydney, and Westmead Millennium Institute for Medical Research at Westmead Hospital, Sydney, Australia. 5. Sydney Translational Imaging Laboratory, Charles Perkins Centre, University of Sydney, Australia. 6. Department of Radiology, Royal Prince Alfred Hospital, Camperdown, Australia. 7. Discipline of Psychiatry, Sydney Medical School, The University of Sydney, Sydney, Australia.
Abstract
BACKGROUND: Childhood maltreatment (CM) history has been associated with poor treatment response in major depressive disorder (MDD), but the mechanisms underlying this relationship remain opaque. Dysfunction in the neural circuits for executive cognition is a putative neurobiological consequence of CM that may contribute importantly to adverse clinical outcomes. We used behavioral and neuroimaging measures of executive functioning to assess their contribution to the relationship between CM and antidepressant response in MDD patients. METHODS: Ninety eight medication-free MDD outpatients participating in the International Study to Predict Optimized Treatment in Depression were assessed at baseline on behavioral neurocognitive measures and functional magnetic resonance imaging during tasks probing working memory (continuous performance task, CPT) and inhibition (Go/No-go). Seventy seven patients completed 8 weeks of antidepressant treatment. Baseline behavioral and neuroimaging measures were assessed in relation to CM (history of childhood physical, sexual, and/or emotional abuse) and posttreatment depression outcomes. RESULTS: Patients with maltreatment exhibited decreased modulation of right dorsolateral prefrontal cortex (DLPFC) activity during working memory updating on the CPT, and a corresponding impairment in CPT behavioral performance outside the scanner. No between-group differences were found for imaging or behavior on the Go/No-go test of inhibition. Greater DLPFC activity during CPT significantly predicted posttreatment symptom improvement in patients without maltreatment, whereas the relationship between DLPFC activity and symptom change was nonsignificant, and in the opposite direction, in patients with maltreatment. CONCLUSIONS: The effect of CM on prefrontal circuitry involved in executive function is a potential predictor of antidepressant outcomes.
BACKGROUND: Childhood maltreatment (CM) history has been associated with poor treatment response in major depressive disorder (MDD), but the mechanisms underlying this relationship remain opaque. Dysfunction in the neural circuits for executive cognition is a putative neurobiological consequence of CM that may contribute importantly to adverse clinical outcomes. We used behavioral and neuroimaging measures of executive functioning to assess their contribution to the relationship between CM and antidepressant response in MDDpatients. METHODS: Ninety eight medication-free MDD outpatients participating in the International Study to Predict Optimized Treatment in Depression were assessed at baseline on behavioral neurocognitive measures and functional magnetic resonance imaging during tasks probing working memory (continuous performance task, CPT) and inhibition (Go/No-go). Seventy seven patients completed 8 weeks of antidepressant treatment. Baseline behavioral and neuroimaging measures were assessed in relation to CM (history of childhood physical, sexual, and/or emotional abuse) and posttreatment depression outcomes. RESULTS:Patients with maltreatment exhibited decreased modulation of right dorsolateral prefrontal cortex (DLPFC) activity during working memory updating on the CPT, and a corresponding impairment in CPT behavioral performance outside the scanner. No between-group differences were found for imaging or behavior on the Go/No-go test of inhibition. Greater DLPFC activity during CPT significantly predicted posttreatment symptom improvement in patients without maltreatment, whereas the relationship between DLPFC activity and symptom change was nonsignificant, and in the opposite direction, in patients with maltreatment. CONCLUSIONS: The effect of CM on prefrontal circuitry involved in executive function is a potential predictor of antidepressant outcomes.
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