Genetic Factors
In 2003 Science published an influential study of Avshalom Caspi et al. who found that a gene-environment interaction (GxE) may explain why life stress is a predictor for depressive episodes in some individuals, but not in others, depending on an allelic variation of the serotonin-transporter-linked promoter region (5-HTTLPR). Soon after, the results were replicated by Kenneth Kendler's group, raising hopes in the psychiatric genetics community. By 2007 there were 11 replications, 3 partial replication and 3 non-replications of this proposed GxE. However, two of the largest studies were negative. Two 2009 meta-analyses were also negative; one included 14 studies, the other just five, owing to different study selection criteria. A 2010 review of studies in this area found 17 replications, 8 partial replications (interaction only in females or only with one of several types of adversity), and 9 non-replications (no interaction or an interaction in the opposite direction). It also found a systematic relationship between the method used to assess environmental adversity and the results of the studies; all studies using objective indicators or structured interviews to assess stress replicated the gene–environment interaction fully or partially, whereas all non-replications relied on brief self-report measures of adversity. This review also found that both 2009 meta-analyses were significantly biased toward negative studies.
Other hypothesized genomic influences are BDNF polymorphisms, but the replications studies have been mixed and insufficient as of 2005 for a meta-analysis. Studies also indicate an association of BDNF to suicidal behavior. However, findings from the gene-environment interactions studies suggest that the current BDNF models of depression are too simplistic. A 2008 study found interactions (biological epistasis) in the signaling pathways of the BDNF and the serotonin transporter; the BDNF Val66Met allele, which was predicted to have reduced responsitivity to serotonin, was found to exercise protective effects in individuals with the short 5-HTTLPR allele that is otherwise believed to predispose individuals to depressive episodes after stressful events. Thus, the BDNF-mediated signalling involved in neuroplastic responses to stress and antidepressants is influenced by other genetic and environmental modifiers.
Read more about this topic: Biology Of Depression
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