Meta-analysis of the BDNF Val66Met polymorphism in major depressive disorder: effects of gender and ethnicity

Abstract

Brain-derived neurotrophic factor (BDNF) is a nerve growth factor that has antidepressant-like effects in animals and may be implicated in the etiology of mood-related phenotypes. However, genetic association studies of the BDNF Val66Met polymorphism (single nucleotide polymorphism rs6265) in major depressive disorder (MDD) have produced inconsistent results. We conducted a meta-analysis of studies comparing the frequency of the BDNF Val66Met-coding variant in depressed cases (MDD) and nondepressed controls. A total of 14 studies involving 2812 cases with DSM-III or -IV defined MDD and 10 843 nondepressed controls met the inclusion criteria. Analyses were stratified either by gender or ethnicity (Asian and Caucasian) because MDD is more prevalent in women and in Caucasians and because BDNF allele frequencies differ by ethnicity. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were provided for allelic analyses (Met versus Val), as well as for genotypic analyses (Met/Met and Val/Met versus Val/Val). In the total sample, the BDNF Val66Met polymorphism was not significantly associated with depression. However, the gender stratified analyses revealed significant effects in both the allelic and genotypic analyses in men (OR MET , 95% CI; 1.27 (1.10-1.47); OR MET/MET , 95% CI; 1.67 (1.19-2.36)). Stratification according to ethnicity did not show significant effects of the Val66Met polymorphism on MDD. Our results suggest that the BDNF Val66Met polymorphism is of greater importance in the development of MDD in men than in women. Future research into gender issues will be of interest.

The BDNF Val66Met Polymorphism Interacts with Maternal Parenting Influencing Adolescent Depressive Symptoms: Evidence of Differential Susceptibility Model

“…Main-effect associations linking maternal parenting and adolescent depressive symptoms emerged as expected, with less positive parenting (warmth and inductive-reasoning) predicting more depressive symptoms, as did more negative parenting (harshness and hostility); these results proved, then, consistent with prior research on Western adolescents (Ge et al 1994b;Kim et al 2009;Kim et al 2013) and Chinese youth (Zhang et al 2015). Also in line with prior work (Verhagen et al 2010), no main effect of the BDNF Val66Met polymorphism on adolescents' depressive symptoms emerged. Especially important given the G 9 E focus of the current inquiry was that no significant association was detected between BDNF genotype and maternal parenting practices, suggesting no gene-environment correlation (rGE).…”

“…The two gender groups did not differ significantly on genotype frequency, v 2 (2, N = 780) = 2.05, p = .36. Consistent with prior findings of ethnic differences in the distribution of BDNF Val66Met polymorphism (Petryshen et al 2010;Verhagen et al 2010), the Met frequency is relatively higher in our Chinese Han sample than that in Caucasian samples.…”

“…The ethnically homogeneous sampling strategy central to the current work excluded the confounding of population stratification, but it also raised the issue of generalizing our findings to other ethnic youth, given the relatively more common Met in Asian populations compared to Caucasian populations (Petryshen et al 2010;Verhagen et al 2010). It is worth noting that previous studies of Europeans and North Americans usually grouped the Val66Met heterozygote and Met/Met homozygote together into a single group for comparison against Val/Val homozygotes.…”

Parental brain‐derived neurotrophic factor genotype, child prosociality, and their interaction as predictors of parents’ warmth

“…Various studies in mice (Advani et al., 2009; Ren‐Patterson et al., 2006) and in humans (Shalev et al., 2009; Verhagen et al., 2010) have shown a sex difference in the effect of BDNF. This difference may be related to the interactions between BDNF and sex hormones such as estradiol (Begliuomini et al., 2007; Sohrabji et al., 1995) and testosterone (Hill et al., 2012; Verhovshek et al., 2010).…”

State of Art of Serum Brain-Derived Neurotrophic Factor in Schizophrenia

“…Great differences in the allelic frequencies for the BDNF Val66Met polymorphism between populations of different ethnic origins have been reported in public databases (http://www.hapmap.org) for the same populations (Tables 3 and 4). In Caucasian subjects, the frequency of the Met allele is 25-32%, whereas in Asian peoples the Met allele is more frequent, around 40-50% (Pivac et al, 2009;Verhagen et al, 2010). These variations among different ethnic groups in the allelic frequencies of the BDNF polymorphism may be caused by either the natural selection of an advantageous allele by unknown environmental issues or through a founder effect.…”