Frontoparietal Activation During Response Inhibition Predicts Remission to Antidepressants in Patients With Major Depression

Biol Psychiatry. 2016 Feb 15;79(4):274-81. doi: 10.1016/j.biopsych.2015.02.037. Epub 2015 Mar 27.


Background: Despite cognitive function impairment in depression, its relationship to treatment outcome is not well understood. Here, we examined whether pretreatment activation of cortical circuitry during test of cognitive functions predicts outcomes for three commonly used antidepressants.

Methods: Eighty medication-free outpatients with major depression and 34 matched healthy controls were included as participants in the International Study to Predict Optimized Treatment in Depression (iSPOT-D) trial. During functional magnetic resonance imaging, participants completed three tasks that assessed core domains of cognitive functions: response inhibition (Go/NoGo), selective attention (oddball), and selective working memory updating (1-back). Participants were randomized to 1 of 3 arms: escitalopram, sertraline (serotonin-specific reuptake inhibitors [SSRI]), or venlafaxine-extended release (serotonin and norepinephrine reuptake inhibitor [SNRI]) therapy. Functional magnetic resonance imaging scans were repeated after 8 weeks of treatment, and remission was assessed using the Hamilton Rating Scale for Depression.

Results: Dorsolateral prefrontal cortex activation during inhibitory "no go" responses was a general predictor of remission, with remitters having the same pretreatment activation as control participants and nonremitters hypoactivating relative to controls. Posttreatment dorsolateral prefrontal cortex activation was reduced in both remitters and controls but not in nonremitters. By contrast, inferior parietal activation differentially predicted remission between SSRI and SNRI medications, with SSRI remitters showing greater pretreatment activation than SSRI nonremitters and the SNRI group showing the opposite pattern.

Conclusions: Intact activation in the frontoparietal network during response inhibition, a core cognitive function, predicts remission with antidepressant treatment, particularly for SSRIs, and may be a potential substrate of the clinical effect of treatment.

Trial registration: NCT01694303.

Keywords: Cognition; Continuous performance; Executive function; Go/NoGo; Major depressive disorder; Remission; Response inhibition; Selective-serotonin reuptake inhibitor; Serotonin-norepinephrine reuptake inhibitor; Sustained attention; Treatment prediction antidepressant.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antidepressive Agents / therapeutic use*
  • Australia
  • Citalopram / therapeutic use*
  • Cognition
  • Depressive Disorder, Major / drug therapy*
  • Executive Function
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Memory, Short-Term
  • Middle Aged
  • Prefrontal Cortex / physiology*
  • Prognosis
  • Psychiatric Status Rating Scales
  • Regression Analysis
  • Remission Induction
  • Sertraline / therapeutic use*
  • Single-Blind Method
  • Treatment Outcome
  • Venlafaxine Hydrochloride / therapeutic use*
  • Young Adult


  • Antidepressive Agents
  • Citalopram
  • Venlafaxine Hydrochloride
  • Sertraline

Associated data