BDNF Val66Met and DRD2 Taq1A polymorphisms interact to influence PTSD symptom severity: A preliminary investigation in a South African population

Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa. Electronic address: .
Progress in Neuro-Psychopharmacology and Biological Psychiatry (Impact Factor: 3.69). 10/2012; 40(1). DOI: 10.1016/j.pnpbp.2012.10.011
Source: PubMed


We evaluated the role that selected variants in serotonin transporter (5-HTT), dopamine receptor 2 (DRD2) and brain-derived neurotrophic factor (BDNF) genes play in PTSD symptom severity in an at-risk population. We also investigated the interaction between the genetic variants to determine whether these variables and the interactions between the variables influenced the severity of PTSD symptoms.

PTSD symptoms were quantitatively assessed using the Davidson Trauma Scale (DTS) in 150 participants from an at-risk South African population. All participants were genotyped for the 5-HTTLPR, DRD2 Taq1A and BDNF Val66Met polymorphisms. Gene-gene interactions were investigated using various linear models. All analyses were adjusted for age, gender, major depressive disorder diagnosis, level of resilience, level of social support and alcohol dependence.

A significant interaction effect between DRD2 Taq1A and BDNF Val66Met variants on DTS score was observed. On the background of the BDNF Val66Val genotype, DTS score increased significantly with the addition of a DRD2 Taq1A A1 allele. However, on the BDNF Met66 allele background, the addition of an A1 allele was found to reduce total DTS score.

This study provides preliminary evidence for an epistatic interaction between BDNF Val66Met and DRD2 Taq1A polymorphisms on the severity of PTSD symptoms, where both too little and too much dopamine can result in increased PTSD symptom severity.

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    • "The BDNF polymorphism has been associated with childhood trauma, with carriers of the " met " variation being particularly sensitive to the impact of child abuse and recent stress (Elzinga et al., 2011). BNDF variations are also considered as modifiers of the risk of childhood trauma in obsessive-compulsive disorder (Hemmings et al., 2013a,b; Suliman et al., 2013) and as mediators of the impact of childhood adversity on lifetime depression (Carver et al., 2011). A plethora of studies demonstrate a connection between the val66met polymorphism of BDNF and PTSD in relation to: extinguishing the fear and startle response (Rattiner et al., 2004; Zhang et al., 2014); PTSD symptomology and severity (Koenen et al., 2009; Frielingsdorf et al., 2010; Hemmings et al., 2013b); psychotic PTSD (Pivac et al., 2012); and the efficacy of PTSD therapy (Felmingham et al., 2013). "
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    • "A nonconservative amino acid substitution (Val66Met, rs6265) has been identified in the BDNF on chromosome 11p14.1 (Sen et al., 2003); however, most studies have found no association (Olff et al., 2005; Lee et al., 2006; Zhang et al., 2006; Valente et al., 2011b). As mentioned previously, a significant interaction between DRD2 Taq1A (rs1800497) and Val66Met (rs6265) predicts PTSD severity (Hemmings et al., 2013). Interestingly, a recent study in humans and rats suggests that BDNF over-expression may be a critical stress response underlying PTSD by showing that the Val66Met allele confers vulnerability to PTSD via startle data and plasma BDNF levels (Zhang et al., 2013). "
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