title: Genetic Contributions of Inflammation to Depression.
abstract: This paper describes the effects of immune genes genetic variants and mRNA expression on depression's risk, severity, and response to antidepressant treatment, through a systematic review on all papers published between 2000 and 2016. Our results, based largely on case-control studies, suggest that common genetic variants and gene-expression pathways are involved in both immune activation and depression. The most replicated and relevant genetic variants include polymorphisms in the genes for interleukin (IL)-1β, IL-6, IL-10, monocyte chemoattractant protein-1, tumor necrosis factor-alpha, C-reactive protein, and phospholipase A2. Moreover, increased blood cytokines mRNA expression (especially of IL-1β) identifies patients that are less likely to respond to conventional antidepressants. However, even for the most replicated findings there are inconsistent results, not only between studies, but also between the immune effects of the genetic variants and the resulting effects on depression. We find evidence that these discrepant findings may be explained, at least in part, by the heterogeneity of the depression immunophenotype, by environmental influences and gene × environment interactions, and by the complex interfacing of genetic variants with gene expression. Indeed, some of the most robust findings have been obtained in patients developing depression in the context of treatment with interferon-alpha, a widely used model to mimic depression in the context of inflammation. Further 'omics' approaches, through GWAS and transcriptomics, will finally shed light on the interaction between immune genes, their expression, and the influence of the environment, in the pathogenesis of depression.
authors.affiliation: Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: Jacob
authors.initials: J
authors.lastname: Barnes
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: Carmine M
authors.identifier: 0000-0002-9132-5091
authors.initials: CM
authors.lastname: Pariante
mesh_terms: D016207:Cytokines / Q000235:genetics*; D003866:Depressive Disorder / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000276:immunology*
chemical_list: D016207:Cytokines