Testing the predictive value of peripheral gene expression for nonremission following citalopram treatment for major depression

Jean-Philippe Guilloux ¹, Sabrina Bassi ², Ying Ding ³, Chris Walsh ⁴, Gustavo Turecki ⁵, George Tseng ⁶, Jill M Cyranowski ⁴, Etienne Sibille ⁷

Affiliations

¹ 1] Université Paris-Sud EA 3544, Faculté de Pharmacie, Châtenay-Malabry, France [2] Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
² 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.
³ Joint CMU-Pitt PhD Program in Computational Biology, University of Pittsburgh, Pittsburgh, PA, USA.
⁴ Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
⁵ McGill Group for Suicide Studies and Depressive Program, Douglas Mental Health Institute, Montréal, QC, Canada.
⁶ 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.
⁷ 1] Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA [2] Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA.

PMID: 25176167
35 References
15 citations

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).

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