title: Testing the predictive value of peripheral gene expression for nonremission following citalopram treatment for major depression.
abstract: Major depressive disorder (MDD) in general, and anxious-depression in particular, are characterized by poor rates of remission with first-line treatments, contributing to the chronic illness burden suffered by many patients. Prospective research is needed to identify the biomarkers predicting nonremission prior to treatment initiation. We collected blood samples from a discovery cohort of 34 adult MDD patients with co-occurring anxiety and 33 matched, nondepressed controls at baseline and after 12 weeks (of citalopram plus psychotherapy treatment for the depressed cohort). Samples were processed on gene arrays and group differences in gene expression were investigated. Exploratory analyses suggest that at pretreatment baseline, nonremitting patients differ from controls with gene function and transcription factor analyses potentially related to elevated inflammation and immune activation. In a second phase, we applied an unbiased machine learning prediction model and corrected for model-selection bias. Results show that baseline gene expression predicted nonremission with 79.4% corrected accuracy with a 13-gene model. The same gene-only model predicted nonremission after 8 weeks of citalopram treatment with 76% corrected accuracy in an independent validation cohort of 63 MDD patients treated with citalopram at another institution. Together, these results demonstrate the potential, but also the limitations, of baseline peripheral blood-based gene expression to predict nonremission after citalopram treatment. These results not only support their use in future prediction tools but also suggest that increased accuracy may be obtained with the inclusion of additional predictors (eg, genetics and clinical scales).
authors.affiliation: 1] Université Paris-Sud EA 3544, Faculté de Pharmacie, Châtenay-Malabry, France [2] Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Guilloux
authors.affiliation: 1] Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA [2] Instituto de Ciencias Básicas y Medicina Experimental, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Bassi
authors.affiliation: Joint CMU-Pitt PhD Program in Computational Biology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Walsh
authors.affiliation: McGill Group for Suicide Studies and Depressive Program, Douglas Mental Health Institute, Montréal, QC, Canada.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Turecki
authors.affiliation: 1] Joint CMU-Pitt PhD Program in Computational Biology, University of Pittsburgh, Pittsburgh, PA, USA [2] Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: George
authors.initials: G
authors.lastname: Tseng
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Jill M
authors.initials: JM
authors.lastname: Cyranowski
authors.affiliation: 1] Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA [2] Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Etienne
authors.initials: E
authors.lastname: Sibille
mesh_terms: D000328:Adult; D001007:Anxiety / Q000097:blood / Q000150:complications / Q000188:drug therapy; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D015283:Citalopram / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003865:Major Depressive Disorder / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D000069550:Machine Learning; D008297:Male; D008957:Models, Genetic; D011237:Predictive Value of Tests; D011569:Psychiatric Status Rating Scales; D011613:Psychotherapy; D012074:Remission Induction; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D015283:Citalopram; D017367:Selective Serotonin Reuptake Inhibitors