Interaction Between FKBP5 and Childhood Trauma and Risk of Aggressive Behavior

LNG/NIAAA, NIH, Rockville, MD 20852, USA.
Archives of general psychiatry (Impact Factor: 13.75). 01/2012; 69(1):62-70. DOI: 10.1001/archgenpsychiatry.2011.152
Source: PubMed

ABSTRACT Childhood trauma may predispose individuals to aggressive behavior, and both childhood trauma and aggressive behavior are associated with hypothalamic-pituitary-adrenal axis dysregulation.
To determine whether there would be an interaction between genetic variation in FKBP5 and childhood trauma in predicting aggressive behavior.
Cross-sectional study. Four FKBP5 single-nucleotide polymorphisms used in previous studies (rs3800373, rs9296158, rs1360780, and rs9470080) were genotyped. Three diplotypes were derived from 2 major putatively functional haplotypes regulating protein expression that were previously associated with glucocorticoid receptor sensitivity.
Penitentiary District of Abruzzo-Molise in central Italy.
A population of 583 male Italian prisoners recruited between 2005 and 2008.
A comprehensive analysis of aggression and impulsivity was undertaken using the Brown-Goodwin Lifetime History of Aggression (BGHA) questionnaire, the Buss-Durkee Hostility Inventory (BDHI), and the Barratt Impulsiveness Scale (BIS). A history of childhood trauma was investigated with the Childhood Trauma Questionnaire. The interaction between the FKBP5 diplotypes and childhood trauma on measures of aggression was analyzed. Analyses were replicated with a second behavioral measure of aggression: violent behavior in jail. Individual single-nucleotide polymorphism analysis was performed.
Childhood trauma had a significant effect on BGHA and BDHI scores but not on BIS scores. We observed a significant influence of the FKBP5 high-expression diplotype on both a lifetime history of aggressive behavior (BGHA) (P = .012) and violent behavior in jail (P = .025) but only in individuals exposed to childhood trauma, in particular to physical abuse. No main effect of the FKBP5 diplotypes was observed.
These data suggest that childhood trauma and variants in the FKBP5 gene may interact to increase the risk of overt aggressive behavior.

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Available from: Marco Sarchiapone, Apr 25, 2014
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    • "Although contradictory findings have also been published (Bevilacqua et al., 2012), together, these results suggest that trauma and impulsivity may indeed exert a multiplier effect on interindividual cognitive emotion regulation differences. Previous studies established a clear link between impulsivity and emotional reactions after trauma exposure in clinical (abuse survivors: Brodsky et al., 2001; accident survivors: Joseph, Dalgleish, Thrasher, & Yule, 1997) and non-clinical samples alike (students: Aidman & Kollaras- Mitsinikos, 2006). "
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    • "Emerging evidence has also begun to suggest that the brain-derived neurotrophic factor gene (BDNF) may be a plasticity gene (e.g., Chen, Li, & McGue, 2012; Gunnar et al., 2012; Juhasz et al., 2011; Mata, Thompson, & Gotlib, 2010; Suzuki et al., 2011), as is the oxytocin receptor gene (OXTR; Johansson et al., 2012; Poulin, Holman, & Buffone, 2012; Sturge-Apple, Cicchetti, Davies, & Suor, 2012) and the FK506 binding protein 5 gene (Bevilacqua et al., 2012; Xie et al., 2010; Zimmermann et al., 2011). There are perhaps less frequent indications of this in the catechol-O-methyltransferase gene (Laucht et al., 2012; Nijmeijer et al., 2010) and, in the previously reviewed literature, the monoamine oxidase A gene (MAOA; Enoch, Steer, Newman, Gibson, & Goldman, 2010; Wakschlag et al., 2010). "
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    • "The genetic polymorphism of rs1360780 in the stress-related FKBP5 gene is reportedly associated with the vulnerability of adults to suffer PTSD symptoms after child abuse (Binder et al., 2008). Furthermore, rs1360780 has been implicated in the relationship between childhood trauma and aggressive behavior (Bevilacqua et al., 2012). Because evolutionary psychological studies imply that male aggression may be associated with impulsivity in intertemporal choice in a complex manner (Wilson and Daly, 2004, 2006; Daly and Wilson, 2005), future studies should examine these associations. "
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