title: Transcriptomics in Interferon-α-Treated Patients Identifies Inflammation-, Neuroplasticity- and Oxidative Stress-Related Signatures as Predictors and Correlates of Depression.
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.
authors.affiliation: Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: Nilay
authors.initials: N
authors.lastname: Hepgul
authors.affiliation: Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.|IRCCS Fatebenefratelli, University of Brescia, Brescia, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Cattaneo
authors.affiliation: Institute of Liver Studies, King's College Hospital, London, UK.
authors.forename: Kosh
authors.initials: K
authors.lastname: Agarwal
authors.affiliation: Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: Sara
authors.initials: S
authors.lastname: Baraldi
authors.affiliation: Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Borsini
authors.affiliation: Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: Chiara
authors.initials: C
authors.lastname: Bufalino
authors.affiliation: Department of Gastroenterology and Hepatology, St George's Hospital, London, UK.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Forton
authors.affiliation: Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: Valeria
authors.initials: V
authors.lastname: Mondelli
authors.affiliation: Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: Naghmeh
authors.initials: N
authors.lastname: Nikkheslat
authors.affiliation: IRCCS Fatebenefratelli, University of Brescia, Brescia, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Lopizzo
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy.
authors.forename: Marco A
authors.identifier: 0000-0002-1699-5060
authors.initials: MA
authors.lastname: Riva
authors.affiliation: Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: Alice
authors.initials: A
authors.lastname: Russell
authors.affiliation: Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Hotopf
authors.affiliation: Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: Carmine M
authors.initials: CM
authors.lastname: Pariante
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D000998:Antiviral Agents / Q000009:adverse effects*; D015331:Cohort Studies; D019295:Computational Biology; D003863:Depression / Q000097:blood / Q000139:chemically induced / Q000175:diagnosis / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D006526:Hepatitis C / Q000188:drug therapy; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects*; D007633:Keratins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D011569:Psychiatric Status Rating Scales; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D011795:Surveys and Questionnaires
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D007633:Keratins