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.

Childhood developmental vulnerabilities associated with early life exposure to infectious and noninfectious diseases and maternal mental illness

“…This is consistent with recent evidence for shared genetic vulnerability for mental and physical disorders (Plummer et al., ). Convergent findings from molecular genetics also indicate that a significant proportion of genetic risk loci are located in genes regulating the immune system (Barnes, Mondelli, & Pariante, ; Ripke et al., ), and emerging functional genomics studies implicate immune system pathways in the neuropathology of severe mental disorders (Avramopoulos et al., ; Wu et al., ). An alternative explanation of shared risk for physical and mental disorders may give prominence to the role of social factors associated with mental illness (e.g., poor diet, financial stress) in contributing to poor physical health among mentally ill women and their families, such that the markers of risk measured here in relation to hospitalization for various medical conditions may be proxy indicators of social disadvantage.…”

A Novel System to Categorize the Symptoms of Systemic Lupus Erythematosus

“…In considering our model, it is important to note that conditions such as depression show evidence of immune system activation as well as a contribution of gene variants for inflammatory mediators that may have roles in SLE (37). In the absence of other genes for lupus, these genes could lead to depression, mood disorders, and other conditions under this rubric.…”

N-3 Polyunsaturated Fatty Acids through the Lifespan: Implication for Psychopathology

“…The antiinflammatory effect exerted by n-3 PUFAs represents one of the most investigated mechanisms. Moreover, chronic inflammation is now considered to be central to the pathogenesis of stress-related disorders such as depression (Barnes et al, 2016). Primarily EPA and in part DHA metabolize into antiinflammatory compounds such as leukotrienes (5 series), prostaglandins (3 series), resolvins, lipoxins, and neuroprotectin D1.…”