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 
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.