title: Abnormal error processing in depressive states: a translational examination in humans and rats.
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.
authors.affiliation: Department of Psychiatry, Harvard Medical School/McLean Hospital, Belmont, MA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Beard
authors.affiliation: Department of Psychiatry, Harvard Medical School/McLean Hospital, Belmont, MA, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Donahue
authors.affiliation: Department of Psychiatry, Harvard Medical School/McLean Hospital, Belmont, MA, USA.
authors.forename: D G
authors.initials: DG
authors.lastname: Dillon
authors.affiliation: Department of Psychiatry, Harvard Medical School/McLean Hospital, Belmont, MA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Van't Veer
authors.affiliation: Department of Psychiatry, Harvard Medical School/McLean Hospital, Belmont, MA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Webber
authors.affiliation: Department of Psychiatry, Harvard Medical School/McLean Hospital, Belmont, MA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Psychiatry, Harvard Medical School/McLean Hospital, Belmont, MA, USA.
authors.forename: E
authors.initials: E
authors.lastname: Barrick
authors.affiliation: Department of Psychiatry, Harvard Medical School/McLean Hospital, Belmont, MA, USA.
authors.forename: K J
authors.initials: KJ
authors.lastname: Hsu
authors.affiliation: Department of Psychiatry, Harvard Medical School/McLean Hospital, Belmont, MA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Foti
authors.affiliation: Research Triangle Institute, Research Triangle Park, NC, USA.
authors.forename: F I
authors.initials: FI
authors.lastname: Carroll
authors.affiliation: Department of Psychiatry, Harvard Medical School/McLean Hospital, Belmont, MA, USA.
authors.forename: W A
authors.initials: WA
authors.lastname: Carlezon
authors.affiliation: Department of Psychiatry, Harvard Medical School/McLean Hospital, Belmont, MA, USA.
authors.forename: T
authors.initials: T
authors.lastname: Björgvinsson
authors.affiliation: Department of Psychiatry, Harvard Medical School/McLean Hospital, Belmont, MA, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Pizzagalli
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use; D001288:Attention; D015928:Cognitive Behavioral Therapy; D003346:Corticotropin-Releasing Hormone / Q000633:toxicity; D003863:Depression / Q000139:chemically induced / Q000503:physiopathology* / Q000523:psychology; D003865:Major Depressive Disorder / Q000503:physiopathology* / Q000523:psychology / Q000628:therapy; D004195:Disease Models, Animal; D005260:Female; D006728:Hormones / Q000633:toxicity; D006801:Humans; D008297:Male; D011597:Psychomotor Performance; D051381:Rats; D011930:Reaction Time; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D006728:Hormones; D003346:Corticotropin-Releasing Hormone