COGNITION-CHILDHOOD MALTREATMENT INTERACTIONS IN THE PREDICTION OF ANTIDEPRESSANT OUTCOMES IN MAJOR DEPRESSIVE DISORDER PATIENTS: RESULTS FROM THE iSPOT-D TRIAL

Depress Anxiety. 2015 Aug;32(8):594-604. doi: 10.1002/da.22368. Epub 2015 Apr 27.

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.

Trial registration: ClinicalTrials.gov NCT00693849.

Keywords: depression; executive function; neuroimaging; prefrontal cortex; stress; treatment outcome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Adult Survivors of Child Abuse*
  • Biomarkers
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / physiopathology*
  • Executive Function / physiology*
  • Female
  • Follow-Up Studies
  • Humans
  • Inhibition, Psychological*
  • Magnetic Resonance Imaging / methods*
  • Male
  • Memory, Short-Term / physiology*
  • Middle Aged
  • Outcome Assessment, Health Care*
  • Prefrontal Cortex / physiopathology*
  • Randomized Controlled Trials as Topic
  • Serotonin Uptake Inhibitors / pharmacology*
  • Young Adult

Substances

  • Biomarkers
  • Serotonin Uptake Inhibitors

Associated data

  • ClinicalTrials.gov/NCT00693849