title: A cognitive-emotional biomarker for predicting remission with antidepressant medications: a report from the iSPOT-D trial.
abstract: Depression involves impairments in a range of cognitive and emotional capacities. It is unknown whether these functions can inform medication choice when considered as a composite predictive biomarker. We tested whether behavioral tests, grounded in the neurobiology of cognitive and emotional functions, predict outcome with common antidepressants. Medication-free outpatients with nonpsychotic major depressive disorder (N=1008; 665 completers) were assessed before treatment using 13 computerized tests of psychomotor, executive, memory-attention, processing speed, inhibitory, and emotional functions. Matched healthy controls (N=336) provided a normative reference sample for test performance. Depressed participants were then randomized to escitalopram, sertraline, or venlafaxine-extended release, and were assessed using the 16-item Quick Inventory of Depressive Symptomatology (QIDS-SR16) and the 17-item Hamilton Rating Scale for Depression. Given the heterogeneity of depression, analyses were furthermore stratified by pretreatment performance. We then used pattern classification with cross-validation to determine individual patient-level composite predictive biomarkers of antidepressant outcome based on test performance. A subgroup of depressed participants (approximately one-quarter of patients) were found to be impaired across most cognitive tests relative to the healthy norm, from which they could be discriminated with 91% accuracy. These patients with generally impaired cognitive task performance had poorer treatment outcomes. For this impaired subgroup, task performance furthermore predicted remission on the QIDS-SR16 at 72% accuracy specifically following treatment with escitalopram but not the other medications. Therefore, tests of cognitive and emotional functions can form a clinically meaningful composite biomarker that may help drive general treatment outcome prediction for optimal treatment selection in depression, particularly for escitalopram.
authors.affiliation: 1] Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA [2] Sierra-Pacific Mental Illness Research, Education, and Clinical Center (MIRECC) Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Etkin
authors.affiliation: 1] Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA [2] Sierra-Pacific Mental Illness Research, Education, and Clinical Center (MIRECC) Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Patenaude
authors.affiliation: Brain Dynamics Center, University of Sydney Medical School and Westmead Millennium Institute for Medical Research at Westmead Hospital, Sydney, NSW, Australia.
authors.forename: Yun Ju C
authors.initials: YJ
authors.lastname: Song
authors.affiliation: Department of General Practice, Sydney Medical School, Westmead, University of Sydney, Sydney, NSW, Australia.
authors.forename: Timothy
authors.initials: T
authors.lastname: Usherwood
authors.affiliation: 1] Brain Resource, Sydney, NSW, Australia [2] Brain Resource, San Francisco, CA, USA.
authors.forename: William
authors.initials: W
authors.lastname: Rekshan
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
authors.forename: Alan F
authors.initials: AF
authors.lastname: Schatzberg
authors.affiliation: Duke-National University of Singapore, Singapore, Singapore.
authors.forename: A John
authors.initials: AJ
authors.lastname: Rush
authors.affiliation: 1] Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA [2] Sierra-Pacific Mental Illness Research, Education, and Clinical Center (MIRECC) Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA [3] Brain Dynamics Center, University of Sydney Medical School and Westmead Millennium Institute for Medical Research at Westmead Hospital, Sydney, NSW, Australia.
authors.forename: Leanne M
authors.initials: LM
authors.lastname: Williams
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000627:therapeutic use*; D015283:Citalopram / Q000627:therapeutic use; D003071:Cognition; D003201:Computers; D003692:Delayed-Action Preparations; D003865:Major Depressive Disorder / Q000175:diagnosis* / Q000188:drug therapy* / Q000523:psychology; D004644:Emotions; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011569:Psychiatric Status Rating Scales; D011581:Psychological Tests; D020280:Sertraline / Q000627:therapeutic use; D016896:Treatment Outcome; D000069470:Venlafaxine Hydrochloride / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D003692:Delayed-Action Preparations; D015283:Citalopram; D000069470:Venlafaxine Hydrochloride; D020280:Sertraline