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-1 beta (IL)-1 beta, tumor necrosis factor-alpha (TNF-alpha) 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-1 beta, 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.
- Immune activation
- SEROTONIN TRANSPORTER GENE
- INTERLEUKIN-1-BETA IL-1-BETA GENE
- ONSET MOOD DISORDERS
- CHRONIC HEPATITIS-C
- MAJOR DEPRESSION
- KOREAN POPULATION
- ANTIDEPRESSANT RESPONSE
- INCREASED RISK
- FUNCTIONAL POLYMORPHISM