COGNITION-CHILDHOOD MALTREATMENT INTERACTIONS IN THE PREDICTION OF ANTIDEPRESSANT OUTCOMES IN MAJOR DEPRESSIVE DISORDER PATIENTS: RESULTS FROM THE iSPOT-D TRIAL.
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.
Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California.|Sierra-Pacific Mental Illness Research, Education, and Clinical Center (MIRECC), Veterans Affairs Palo Alto Health Care System, Palo Alto, California.
Shefali
S
Miller
Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California.|Sierra-Pacific Mental Illness Research, Education, and Clinical Center (MIRECC), Veterans Affairs Palo Alto Health Care System, Palo Alto, California.
Lisa M
LM
McTeague
Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California.|Sierra-Pacific Mental Illness Research, Education, and Clinical Center (MIRECC), Veterans Affairs Palo Alto Health Care System, Palo Alto, California.|Department of Psychology, Stanford University, Stanford, California.
Anett
A
Gyurak
Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California.|Sierra-Pacific Mental Illness Research, Education, and Clinical Center (MIRECC), Veterans Affairs Palo Alto Health Care System, Palo Alto, California.
Brian
B
Patenaude
Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California.|Sierra-Pacific Mental Illness Research, Education, and Clinical Center (MIRECC), Veterans Affairs Palo Alto Health Care System, Palo Alto, California.
Leanne M
LM
Williams
Brain Dynamics Center, Sydney Medical School, The University of Sydney, and Westmead Millennium Institute for Medical Research at Westmead Hospital, Sydney, Australia.|Sydney Translational Imaging Laboratory, Charles Perkins Centre, University of Sydney, Australia.|Department of Radiology, Royal Prince Alfred Hospital, Camperdown, Australia.
Stuart M
SM
Grieve
Brain Dynamics Center, Sydney Medical School, The University of Sydney, and Westmead Millennium Institute for Medical Research at Westmead Hospital, Sydney, Australia.|Discipline of Psychiatry, Sydney Medical School, The University of Sydney, Sydney, Australia.
Mayuresh S
MS
Korgaonkar
Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California.|Sierra-Pacific Mental Illness Research, Education, and Clinical Center (MIRECC), Veterans Affairs Palo Alto Health Care System, Palo Alto, California.
Amit
A
Etkin
D000328:Adult; D054523:Adult Survivors of Child Abuse; D015415:Biomarkers; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology*; D056344:Executive Function / Q000502:physiology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007266:Inhibition, Psychological; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology*; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D017397:Prefrontal Cortex / Q000503:physiopathology*; D016032:Randomized Controlled Trials as Topic; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D055815:Young Adult
D015415:Biomarkers; D017367:Selective Serotonin Reuptake Inhibitors
depression; executive function; neuroimaging; prefrontal cortex; stress; treatment outcome