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: 4.03). 10/2012; DOI: 10.1016/j.pnpbp.2012.10.011
Source: PubMed

ABSTRACT BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: This study provides preliminary evidence for an epistatic effect 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.

1 Bookmark
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: a b s t r a c t Posttraumatic stress disorder (PTSD) is a complex syndrome that occurs following exposure to a poten-tially life threatening traumatic event. This review summarises the literature on the genetics of PTSD including gene–environment interactions (GxE), epigenetics and genetics of treatment response. Numer-ous genes have been shown to be associated with PTSD using candidate gene approaches. Genome-wide association studies have been limited due to the large sample size required to reach statistical power. Studies have shown that GxE interactions are important for PTSD susceptibility. Epigenetics plays an important role in PTSD susceptibility and some of the most promising studies show stress and child abuse trigger epigenetic changes. Much of the molecular genetics of PTSD remains to be elucidated. However, it is clear that identifying genetic markers and environmental triggers has the potential to advance early PTSD diagnosis and therapeutic interventions and ultimately ease the personal and financial burden of this debilitating disorder.
    Journal of Anxiety Disorders 12/2014; 28:873-883. · 2.96 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Treatment for Post-Traumatic Stress Disorder (PTSD) is not always effective, and as the increasing demand for better management of PTSD and combat-related PTSD (CR-PTSD) infiltrates the UK media, so does a pressing need to understand individual variance in disease aetiology. Recent research in psychology, neuroscience and genetics has separately investigated how and why PTSD affects individuals differently. Here, we report on research on trauma, spatial processing and genetics to demonstrate that the hippocampus, part of the medial temporal lobe, is key to understanding how genes and environment interact to determine susceptibility to, and successful recovery from, PTSD. We argue that the integration of these research disciplines will bring new possibilities for prevention and treatment of PTSD within the Ministry of Defence (MOD), emergency services, National Health Service (NHS) and beyond.
    Frontiers in Human Neuroscience 01/2014; 8:100. · 2.90 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Some recent studies show an association between a functional polymorphism of BDNF gene (Val66Met) and the susceptibility to nicotine dependence and we hypothesized that this polymorphism was associated with smoking in both schizophrenia patients and healthy controls. The BDNF Val66Met gene polymorphism was genotyped in 690 chronic male schizophrenia patients (smoker/nonsmoker= 522/169) and 628 male controls (smoker/nonsmoker=322/306) using a case–control design. Nicotine dependence (ND) was assessed by the cigarettes smoked per day (CPD), the Heaviness of Smoking Index (HSI), and the Fagerstrom Test for ND (FTND). Patients also were rated on the Positive and Negative Symptom Scale (PANSS). The results showed no significant differences in BDNF Val66Met genotype and allele distributions between the patients and healthy controls or between smokers and nonsmokers in either patients or healthy controls alone. In patient groups, however, the smokers with the Met allele had significantly higher HSI scores (Met/Met: 2.8±1.7 vs. Met/Val: 2.2±1. 7 vs.Val/Val: 2.0±1.6, p<0.01) and a trend toward a significantly higher FTND score (p=0.09) than those with the Val/Val genotype. In addition, the smokers showed significantly lower PANSS negative symptom and total scores, longer duration of illness and more hospitalizations (all p<0.05). In the control group, the smokers with the Met allele started smoking significantly earlier than those with the Val/Val genotype (both p<0.05). These results suggest that the BDNF Val66Met polymorphism may affect a smoker’s response to nicotine in both schizophrenia and healthy controls from a Chinese Han population, but with differential effects in different aspects of smoking behaviors.
    Journal of Psychiatric Research 10/2014; · 4.09 Impact Factor