The Val66Met Coding Variant of the Brain-Derived Neurotrophic Factor (BDNF) Gene Does Not Contribute Toward Variation in the Personality Trait Neuroticism

Department of Public Health and Primary Care, University of Cambridge, Cambridge, England, United Kingdom
Biological Psychiatry (Impact Factor: 10.26). 12/2005; 58(9):738-42. DOI: 10.1016/j.biopsych.2005.05.014
Source: PubMed


The val66met variant located within the brain-derived neurotrophic factor gene (BDNF) has previously been associated with human neuroticism, a dimension of personality strongly predictive of depressive illness.
Here we report an attempt to replicate this association using three populations of extreme neuroticism scorers derived from two large English cohorts (n = 88,142 and n = 20,921). On the basis of the current literature, which indicates that an effect of BDNF may only become apparent in those individuals exposed to stress, a gene-environment interaction was also sought.
No statistically significant effects were identified, although simulations indicated that the samples held sufficient power to detect a main effect accounting for just .75% of variation and an interaction accounting for 4% of variation.
These data do not support the hypothesis that the val66met BDNF polymorphism contributes toward variation in the human personality trait neuroticism, at least as indexed by the Eysenck Personality Questionnaire.

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    • "This polymorphism affects hippocampal function and memory processes (Egan et al., 2003; Hariri et al., 2003; Pezawas et al., 2004). The Met-allele has been associated with lower five-factor model neuroticism in a Caucasian sample (Sen et al., 2003; Hünnerkopf et al., 2007) and extraversion in Japanese female participants (Itoh et al., 2004), but replications have yielded very inconsistent results (Tsai et al., 2004; Willis-Owen et al., 2005; Tochigi et al., 2006). "
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    ABSTRACT: The purpose of this study was to investigate the effects of the 5-HTTLPR and brain-derived neurotrophic factor (BDNF) Val66Met polymorphisms on self-reported Big Five personality traits and their facets in a population representative sample of adolescents. The sample consisted of both cohorts of the Estonian Children Personality Behaviour and Health Study, and personality data were collected during its second waves. The 5-HTTLPR and BDNF Val66Met polymorphisms were genotyped. The BDNF Val66Met had a significant effect on conscientiousness [F(1,807)=4.32, P=0.038]. We did not find effects of the 5-HTTLPR polymorphism on the main domains of personality, however, a gene×gene interaction on conscientiousness emerged -BDNF Val66Met Met-allele carriers with the 5-HTTLPR s/s genotype had by far the lowest scores in conscientiousness [F(2,803)=4.38, P=0.012]. In addition, we found genotype effects on some facet scales. In conclusion, the BDNF Val66Met genotype Met-allele carriers have lower conscientiousness, and this effect is increased in the 5-HTTLPR s/s individuals.
    Full-text · Article · Oct 2011 · Psychiatric genetics
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    • "The brain-derived neurotrophic factor (BDNF) gene is a plausible candidate gene for NE (Willis-Owen et al., 2005). BDNF is a nerve growth factor that is assigned a central role in many neurobiological models of the pathophysiology of depression (Duman & Monteggia, 2006). "
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    ABSTRACT: The brain-derived neurotrophic factor (BDNF) gene is a plausible candidate for early-emerging negative emotionality (NE), and evidence suggests that the effects of this gene may be especially salient in the context of familial risk for child maladjustment. We therefore examined whether the single-nucleotide polymorphism producing a valine-to-methionine substitution at codon 66 (val66met) of the BDNF gene was associated with childhood NE, in the context of parental depression and relationship discord. A sample of 413 three-year-old children was assessed for NE using standardized laboratory measures. The children's parents completed clinical interviews as well as a measure of marital satisfaction. Children with at least one BDNF methionine (met) allele exhibited elevated NE when a parent had a history of depressive disorder or when relationship discord was reported by a parent. In contrast, this allele was associated with especially low NE when parental depression was absent and when the parental relationship was not discordant. Our findings suggest that the BDNF met allele confers increased child sensitivity to both positive and negative familial influences.
    Full-text · Article · Oct 2010 · Psychological Science
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    • "Support for this hypothesis comes from recent studies showing enhanced sensitivity to environmental enrichment and chronic unpredictable stress in heterozygous BDNF knockout mice (Chourbaji et al. 2008; Autry et al. 2009). Second, a common non-synonymous polymorphism in human BDNF, Val66Met, compromises protein processing, activity-dependent secretion and neural activity (Egan et al. 2003; Hariri et al. 2003), and has been associated with altered anxiety-related traits in some (Sen et al. 2003; Lang et al. 2005), but not all studies (Jiang et al. 2005; Willis-Owen et al. 2005; Martinowich et al. 2007). In one recent study (Gatt et al. 2009), Val66Met carriers were found to be more sensitive to early environmental factors, showing increased risk for depression and anxiety, and cognitive alterations in the presence of early life stress. "
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    ABSTRACT: Anxiety is known to be influenced by both adverse childhood experiences and genetic susceptibility factors. A polymorphism in the brain-derived neurotrophic factor (BDNF) gene modulates the association between adverse early experiences and risk for anxiety and depression in adulthood. An animal model of this gene-by-environment risk factor is lacking. Using two different early environmental manipulations, we found that a heterozygous null mutation in the mouse BDNF gene moderated the long-term effect of maternal care on innate anxiety behavior. Although changes in maternal care were associated with mild changes in anxiety in wild-type mice, this effect was magnified in heterozygous null BDNF mice with high- and low-maternal care associated with low and high levels, respectively, of avoidance behavior as measured in the open field and elevated plus maze tests. These data argue for an increased sensitivity to early environmental influences of mice with reduced BDNF function and support the important role of this neurotrophic factor in the developmental plasticity of brain circuits controlling anxiety.
    Full-text · Article · Jun 2010 · Genes Brain and Behavior
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