Risk and protective effects of serotonin and BDNF genes on stress-related adult psychiatric symptoms

Abstract

We focused on individual risk by examining childhood adversity and current psychiatric symptoms in a sample of 100 college students genotyped for both the serotonin transporter (5-HTTLPR) and the brain-derived neurotrophic factor (BDNF). Naturally occurring allelic variation in 5-HTTLPR (short/long) and BDNF (valine/methionine) have been strongly implicated in stress-related psychiatric risk, but the combined effects of these alleles on psychological functioning have yet to be fully elucidated. Univariate analysis revealed gene-environment correlations linking heightened psychiatric risk with past childhood adversity for short but not long 5-HTTLPR allelic carriers and for valine (Val) but not methionine (Met) BDNF allelic carriers. Multivariate analyses revealed a significant gene x gene interaction with results showing that risk varied systematically depending on both 5-HTTLPR and BDNF alleles, independent of childhood adversity. Hierarchical regression analyses indicated that approximately 11% of the variance in symptoms of depression could be specifically accounted for by the epistatic interaction of 5-HTTLPR and BDNF val66Met polymorphisms. Allelic group analyses indicated lowest risk, as measured by depression and anxiety, for allelic carriers of 5-HTTLPR-short and BDNF Met, followed by 5-HTTLPR-long and BDNF-Val, 5-HTTLPR-short and BDNF-Val, and 5-HTTLPR-long and BDNF-Met. Results suggest that protective or risk-enhancing effects on stress-related psychiatric functioning may depend on specific allelic combinations of 5-HTTLPR and BDNF.

Peripheral blood levels of brain-derived neurotrophic factor in patients with post-traumatic stress disorder (PTSD): A systematic review and meta-analysis

“…The possible limitation of the present study is the absence of proBDNF measures in the remaining studies rather than Aksu [ 8 ]. Based on prior investigations on the role of BDNF among people with MDD, although BDNF may be significantly lower in the disease group compared to the normal controls, the difference of proBDNF levels between MDD patients and the healthy population was not significant [ 65 ].…”

“…However, the evidence is not conclusive about the effect of BDNF Val66Met polymorphism on PTSD as a recent meta-analysis of 11 studies estimated a marginal effect of this polymorphism on the risk of PTSD [ 64 ]. It is noteworthy to mention that multivariate analyses indicate that the presence of the serotonin transporter (5-HTTLPR) variant further strengthens the correlation between BDNF Val66Met polymorphism and the risk of PTSD in adults [ 65 ]. Also, Met allele carriers have impaired fear extinction and decreased hippocampal volume and function that are all observed in individuals with PTSD [ 66 ].…”

Genotype-expression interactions for BDNF across human brain regions

“…Indeed, alterations in BDNF peripheral blood (leukocyte) gene expression and protein levels have been shown to be a significant biomarker for many of these disorders [ 6 , 7 ]. Genetic variations within BDNF may induce inappropriate expression and result in breakdown of proper cell signaling, and several variants in this gene have similarly been associated with various neuropsychiatric disorders [ 8 , 9 ]. Conversely, restoration to normal homeostatic conditions has been shown to improve the symptoms caused by these conditions, as occurs when BDNF-targeted neurotrophic pharmaceuticals are given to patients [ 10 ].…”

Clustering suicidal phenotypes and genetic associations with brain-derived neurotrophic factor in patients with substance use disorders

“…Finally, the lack of data regarding childhood trauma and impulsivity is a potentially important limitation of this study. Sexual abuse notably increases the risk for SA in populations with mental disorders 83 , especially for ‘recurrent’ SA 84 , possibly in interaction with variations in the BDNF gene 22 , 85 . However, the latter associations rather regarded depression and anxiety than SA itself 24 , 72 .…”