Abnormal error processing in depressive states: a translational examination in humans and rats

Transl Psychiatry. 2015 May 12;5(5):e564. doi: 10.1038/tp.2015.54.

Abstract

Depression has been associated with poor performance following errors, but the clinical implications, response to treatment and neurobiological mechanisms of this post-error behavioral adjustment abnormality remain unclear. To fill this gap in knowledge, we tested depressed patients in a partial hospital setting before and after treatment (cognitive behavior therapy combined with medication) using a flanker task. To evaluate the translational relevance of this metric in rodents, we performed a secondary analysis on existing data from rats tested in the 5-choice serial reaction time task after treatment with corticotropin-releasing factor (CRF), a stress peptide that produces depressive-like signs in rodent models relevant to depression. In addition, to examine the effect of treatment on post-error behavior in rodents, we examined a second cohort of rodents treated with JDTic, a kappa-opioid receptor antagonist that produces antidepressant-like effects in laboratory animals. In depressed patients, baseline post-error accuracy was lower than post-correct accuracy, and, as expected, post-error accuracy improved with treatment. Moreover, baseline post-error accuracy predicted attentional control and rumination (but not depressive symptoms) after treatment. In rats, CRF significantly degraded post-error accuracy, but not post-correct accuracy, and this effect was attenuated by JDTic. Our findings demonstrate deficits in post-error accuracy in depressed patients, as well as a rodent model relevant to depression. These deficits respond to intervention in both species. Although post-error behavior predicted treatment-related changes in attentional control and rumination, a relationship to depressive symptoms remains to be demonstrated.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Antidepressive Agents / therapeutic use
  • Attention*
  • Cognitive Behavioral Therapy
  • Corticotropin-Releasing Hormone / toxicity
  • Depression / chemically induced
  • Depression / physiopathology*
  • Depression / psychology
  • Depressive Disorder, Major / physiopathology*
  • Depressive Disorder, Major / psychology
  • Depressive Disorder, Major / therapy
  • Disease Models, Animal
  • Female
  • Hormones / toxicity
  • Humans
  • Male
  • Psychomotor Performance*
  • Rats
  • Reaction Time
  • Treatment Outcome
  • Young Adult

Substances

  • Antidepressive Agents
  • Hormones
  • Corticotropin-Releasing Hormone