The role of immune genes in the association between depression and inflammation: a review of recent clinical studies.

The role for dysregulation of the immune system in the pathogenesis of depressive disorder is well established, and emerging research suggests the role of an underlying genetic vulnerability. The purpose of this review is to summarize the existing literature on the genetic variants involved in neurobiological pathways associated with both immune activation and depression. Using PubMed, Scopus, The Cochrane Library, Embase, Ovid of Medline, PsycINFO and ISI web of Knowledge, we selected 52 papers which are relevant for this literature review. Findings across the literature suggest that functional allelic variants of genes for interleukin-1beta (IL)-1ß, tumor necrosis factor-alpha (TNF-α) and C-reactive protein (CRP), as well as genetic variations affecting T-cell function, may increase the risk for depression. Moreover, single nucleotide polymorphisms (SNPs) in the IL-1ß, IL-6 and IL-11 genes, and in those regulating T-cell function may be associated with reduced responsiveness to antidepressant therapy. There is also some evidence indicative of a role of genetic variants of the enzymes, Cyclo-oxygenase2 (COX-2) and Phospholipase2 (PLA2), in the aetiology of depression. Finally, SNPs in genes related to the serotonin pathway may play a fundamental role in the shared genetic liability to both immune activation and depressive symptoms. Our review confirms that genetic variants influence the biological mechanisms by which the innate immune system contributes to the development of depression. However, future studies are necessary to identify the molecular mechanisms underlying these associations.

Depression and anxiety in patients receiving interferon-alpha: The role of illness perceptions.

Development of psychiatric symptoms during interferon-alpha therapy may be influenced by psychological factors. We examined illness perceptions using the Revised Illness Perceptions Questionnaire in 55 patients with chronic hepatitis C virus infection, due to receive interferon-alpha. The Hospital Anxiety and Depression Scale was used to assess the development of symptoms. Negative identity, consequences and emotional representation beliefs were significantly associated with both higher depression and anxiety scores. Negative illness perceptions play a predictive role in the development of interferon-alpha-induced psychiatric symptoms.

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

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.