Genetic susceptibility to family environment: BDNF Val66met and 5-HTTLPR influence depressive symptoms.

Abstract

Functional genetic polymorphisms associated with Brain-Derived Neurotrophic Factor (BDNF) and serotonin (5-HTTLPR) have demonstrated associations with depression in interaction with environmental stressors. In light of evidence for biological connections between BDNF and serotonin, it is prudent to consider genetic epistasis between variants in these genes in the development of depressive symptoms. The current study examined the effects of val66met, 5-HTTLPR, and family environment quality on youth depressive symptoms in adolescence and young adulthood in a longitudinal sample oversampled for maternal depression history. A differential susceptibility model was tested, comparing the effects of family environment on depression scores across different levels of a cumulative plasticity genotype, defined as presence of both, either, or neither plasticity alleles (defined here as val66met Met and 5-HTTLPR ‘S’). Cumulative plasticity genotype interacted with family environment quality to predict depression among males and females at age 15. After age 15, however, the interaction of cumulative plasticity genotype and early family environment quality was only predictive of depression among females. Results supported a differential susceptibility model at age 15, such that plasticity allele presence was associated with more or less depressive symptoms depending on valence of the family environment, and a diathesis-stress model of gene-environment interaction after age 15. These findings, although preliminary because of the small sample size, support prior results indicating interactive effects of 5-HTTLPR, val66met, and environmental stress, and suggest that family environment may have a stronger influence on genetically susceptible women than men.

BDNFVal66Met polymorphism moderates the link between child maltreatment and reappraisal ability

“…The assessment of alternative G × E models supported a strong differential susceptibility model, suggesting that BDNF Met carriers are both able to benefit from better childhood care (as indicated by low CECA.Q scores) and more vulnerable to child maltreatment. This complements previous results related to depression, which showed that the BDNF Met allele is associated both with the lowest and the highest vulnerability to depression depending on the quality of family environment (Dalton et al ) and the history of child maltreatment (Frodl et al ).…”

“…It has been recently argued that genotypes may be associated with differential susceptibility to environment, resulting in both greater costs from environmental adversity and greater benefits from environmental support (Belsky & Pluess ; Belsky et al ). This hypothesis has been supported in the case of the BDNF Val66Met polymorphism and family environment, with Met carriers showing higher depressive symptoms in negative family environment and lower depressive symptoms in positive family environments (Dalton et al ). Similarly, a reduced volume of hippocampal regions, which had been associated with depression, was found in BDNF Met allele carriers with a history of child maltreatment, whereas a larger volume was observed in non‐maltreated people with the same genotype (Frodl et al ).…”

Cortisol secretion moderates the association between mother–infant attachment at 17 months and child behavior at age 5 years

“…Although this is a relatively small sample, larger samples have also found different interaction models to emerge based on seemingly minor changes in methodology (e.g. Dalton et al, ; Ludmer et al, ; Roisman et al, ). As argued by Del Giudice (), statistical classifications of interaction type have several limitations (e.g.…”

Partial replication of two rumination-related candidate gene studies

“…One well-studied SNP in the BDNF gene is the valine to methionine substitution at codon 66 (val66met). Evidence indicates that BDNF val66met plays a role in depressive symptoms in children and adolescents (Dalton, Hammen, Najman, & Brennan, 2014) as well as cognitive response style (Hilt, Sander, Nolen-Hoeksema, & Simen, 2007; Stone et al, 2013). Of the relatively few studies examining the BDNF val66met polymorphism in relation to cognitive response style, two indicated that the Val/Val genotype was associated with higher rumination in late childhood and early adolescence (Hilt et al, 2007; Stone et al, 2013).…”