Transcriptomics in Interferon-α-Treated Patients Identifies Inflammation-, Neuroplasticity- and Oxidative Stress-Related Signatures as Predictors and Correlates of Depression

Nilay Hepgul*, Annamaria Cattaneo, Kosh Agarwal, Sara Baraldi, Alessandra Borsini, Chiara Bufalino, Daniel M. Forton, Valeria Mondelli, Naghmeh Nikkheslat, Nicola Lopizzo, Marco Andrea Riva, Alice Elizabeth Russell, Matthew Hugo Hotopf, Carmine Maria Pariante

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

47 Citations (Scopus)
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Abstract

Owing to the unique opportunity to assess individuals before and after they develop depression within a short timeframe, interferon-α (IFN-α) treatment for chronic hepatitis C virus (HCV) infection is an ideal model to identify molecular mechanisms relevant to major depression, especially in the context of enhanced inflammation. Fifty-eight patients were assessed prospectively, at baseline and monthly over 24 weeks of IFN-α treatment. New-onset cases of depression were determined using the Mini International Neuropsychiatric Interview (MINI). Whole-blood transcriptomic analyses were conducted to investigate the following: (1) baseline gene expression differences associated with future development of IFN-α-induced depression, before IFN-α, and (2) longitudinal gene expression changes from baseline to weeks 4 or 24 of IFN-α treatment, separately in those who did and did not develop depression. Transcriptomics data were analyzed using Partek Genomics Suite (1.4-fold, FDR adjusted p⩽0.05) and Ingenuity Pathway Analysis Software. Twenty patients (34%) developed IFN-α-induced depression. At baseline, 73 genes were differentially expressed in patients who later developed depression compared with those who did not. After 4 weeks of IFN-α treatment, 592 genes were modulated in the whole sample, representing primarily IFN-α-responsive genes. Substantially more genes were modulated only in patients who developed depression (n=506, compared with n=70 in patients who did not), with enrichment in inflammation-, neuroplasticity- and oxidative stress-related pathways. A similar picture was observed at week 24. Our data indicate that patients who develop IFN-α-induced depression have an increased biological sensitivity to IFN-α, as shown by larger gene expression changes, and specific signatures both as predictors and as correlates.Neuropsychopharmacology advance online publication, 27 April 2016; doi:10.1038/npp.2016.50.

Original languageEnglish
Pages (from-to)2502–2511
JournalNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
Volume41
Early online date27 Apr 2016
DOIs
Publication statusE-pub ahead of print - 27 Apr 2016

Keywords

  • Depression
  • Inflammation
  • Gene expression analysis
  • Transcriptomics
  • Microarray

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