BDNF Val66Met is Associated with Introversion and Interacts with 5-HTTLPR to Influence Neuroticism

Abstract

Brain-derived neurotrophic factor (BDNF) regulates synaptic plasticity and neurotransmission, and has been linked to neuroticism, a major risk factor for psychiatric disorders. A recent genome-wide association (GWA) scan, however, found the BDNF Val66Met polymorphism (rs6265) associated with extraversion but not with neuroticism. In this study, we examine the links between BDNF and personality traits, assessed using the Revised NEO Personality Inventory (NEO-PI-R), in a sample from SardiNIA (n ¼ 1560) and the Baltimore Longitudinal Study of Aging (BLSA; n ¼ 1131). Consistent with GWA results, we found that BDNF Met carriers were more introverted. By contrast, in both samples and in a meta-analysis inclusive of published data (n ¼ 15251), we found no evidence for a main effect of BDNF Val66Met on neuroticism. Finally, on the basis of recent reports of an epistatic effect between BDNF and the serotonin transporter, we explored a Val66Met  5-HTTLPR interaction in a larger SardiNIA sample (n ¼ 2333). We found that 5-HTTLPR LL carriers scored lower on neuroticism in the presence of the BDNF Val variant, but scored higher on neuroticism in the presence of the BDNF Met variant. Our findings support the association between the BDNF Met variant and introversion and suggest that BDNF interacts with the serotonin transporter gene to influence neuroticism.

No gene-by-environment interaction of BDNF Val66Met polymorphism and childhood maltreatment on anxiety sensitivity in a mixed race adolescent sample

“…These findings suggest that the BDNF Val66Met polymorphism does not have a direct effect on AS. This finding is in line with studies that have found no significant direct association between BDNF Val66Met polymorphism and personality traits such as neuroticism or harm avoidance and anxiety disorders or mood disorders, including OCD, panic disorder, PTSD and depression (Arias et al, 2012; Chen et al, 2013; Frustaci et al, 2008; Hong et al, 2012; Minelli et al, 2011; Surtees et al, 2007; Terracciano et al, 2010), despite some studies reporting such associations (Frustaci et al, 2008; Lang et al, 2005; Min et al, 2013; Montag et al, 2010; Sen et al, 2003; Terracciano et al, 2010). Firstly, the grouping of Met66 allele carriers (i.e.…”

“…Further support for the aforementioned is reflected in findings of gene x gene and gene x gene x environment interactions which are indicative of significant interaction effects of the BDNF Val66Met polymorphism and the serotonin transporter gene ( SLC6A4 ) on anxiety-related traits (e.g. neuroticism and harm avoidance) (Arias et al, 2012; Terracciano et al, 2010) and depressive symptoms and disorder (Gutiérrez et al, 2015; Kaufman et al, 2006). Finally, the effects of environmental influences other than CM, such as parenting rearing practices (Ibarra et al, 2014) and general self-efficacy (Schiele et al, 2016), on AS should be explored.…”

“…Previous studies have found associations between the Met66 allele and increased introversion (Terracciano et al, 2010), harm avoidance (Montag, Basten, Stelzel, Fiebach, & Reuter, 2010), tendency to ruminate (Beevers, Wells, & McGeary, 2009), lower levels of conscientiousness (Hiio et al, 2011), an increased vulnerability to stress (Casey et al, 2009), increased anxiety-related behaviours (Chen et al, 2006) and increased risk of an anxiety disorder in children and adolescents (Tocchetto et al, 2011). In contrast, other studies have reported an association between the Val66 allele and higher neuroticism scores, as well as increased risk of anxiety symptoms during adolescence (Chen, Yu, Liu, Zhang, & Zhang, 2015; Frustaci et al, 2008).…”

“…Some studies have reported associations between the BDNF Val66Met polymorphism and personality traits such as trait anxiety and neuroticism (Lang et al, 2005; Sen et al, 2003), while others have not (Terracciano et al, 2010; Willis-Owen et al, 2005). Previous studies have found associations between the Met66 allele and increased introversion (Terracciano et al, 2010), harm avoidance (Montag, Basten, Stelzel, Fiebach, & Reuter, 2010), tendency to ruminate (Beevers, Wells, & McGeary, 2009), lower levels of conscientiousness (Hiio et al, 2011), an increased vulnerability to stress (Casey et al, 2009), increased anxiety-related behaviours (Chen et al, 2006) and increased risk of an anxiety disorder in children and adolescents (Tocchetto et al, 2011).…”

Cerebral 5-HT2A Receptor and Serotonin Transporter Binding in Humans Are Not Affected by the val66met BDNF Polymorphism Status or Blood BDNF Levels

“…In line with this, a positron emission tomography (PET) study of 25 healthy individuals showed that the val/val genotype was associated with increased SERT binding in men (Henningsson et al, 2009). In addition, a val66met interaction with the 5-HTTLPR (5-HT-transporter-linked promoter region) polymorphism in relation to neuroticism (a risk factor for developing major depression) has been reported (Terracciano et al, 2010).…”