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

TitleTesting the predictive value of peripheral gene expression for nonremission following citalopram treatment for major depression.
Publication TypeJournal Article
Year of Publication2015
AuthorsGuilloux J-P, Bassi S, Ding Y, Walsh C, Turecki G, Tseng G, Cyranowski JM, Sibille E
JournalNeuropsychopharmacology
Volume40
Issue3
Pagination701-10
Date Published2015 Feb
ISSN1740-634X
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).

DOI10.1038/npp.2014.226
Alternate JournalNeuropsychopharmacology
PubMed ID25176167
PubMed Central IDPMC4289958
Grant ListK02 MH084060 / MH / NIMH NIH HHS / United States
MH084060 / MH / NIMH NIH HHS / United States
MH085874 / MH / NIMH NIH HHS / United States
MH086637 / MH / NIMH NIH HHS / United States
R01 MH077159 / MH / NIMH NIH HHS / United States
R21 MH086637 / MH / NIMH NIH HHS / United States