Browsing by Author "Seedat, Soraya"
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Item BDNF Val66Met and DRD2 Taq1A polymorphisms interact to influence PTSD symptom severity: A preliminary investigation in a South African population(Elsevier, 2013) Hemmings, Sian M.J.; Martin, Lindi I.; Klopper, Marisa; van der Merwe, Lize; Aitken, Lisa; de Wit, Erika; Black, Gillian F.; Hoal, Eileen G.; Walzl, Gerhard; Seedat, SorayaBACKGROUND: 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.Item BDNF Val66Met modifies the risk of childhood trauma on obsessive-compulsive disorder(Elsevier, 2013) Hemmings, Sian Megan Joanna; Lochner, Christine; van der Merwe, Lize; Cath, Danielle C.; Seedat, Soraya; Stein, Dan J.Childhood trauma has been linked to the development of later psychopathology, including obsessive-compulsive disorder (OCD). Although evidence exists to suggest that genetic and environmental factors are involved in the aetiology of OCD, little attention has been paid to the interactions that exist between genes and environment. The aim of this study was to investigate gene-by-environment interactions between childhood trauma and the BDNF Val66Met variant in patients with OCD. Childhood trauma was assessed in 134 OCD patients and 188 controls using the Childhood Trauma Questionnaire (CTQ). Linear regression models were used for statistical analyses. Geneeenvironment interactions were estimated by including a combined genotype and CTQ score in the models as interaction terms. All analyses were adjusted for age, gender, CTQ minimisation-denial score and home language by including them in the logistic regression models as covariates. Childhood trauma, specifically emotional abuse and neglect, increased the odds of having OCD significantly (p < 0.001). Although no significant association was observed between BDNF Val66Met and the development of OCD, interaction analysis indicated that the BDNF Met-allele interacted with childhood emotional abuse to increase the risk of OCD significantly in a dose-dependent manner (p < 0.024). To our knowledge, this is one of the first studies to investigate geneeenvironment interactions in OCD, and the findings indicate the importance of collating genetic and environmental variables in future studies.Item No association between cumulative traumatic experiences and sex in risk for posttraumatic stress disorder among human immunodeficiency virus-positive adults(Lippincott, Williams & Wilkins, 2013) Morris, Tanya; Naidoo, Pamela; Cloete, Karen J.; Harvey, Justin; Seedat, SorayaThis study examined the association between the type and number of traumatic experiences and the conditional risk for posttraumatic stress disorder (PTSD), stratified by sex, in human immunodeficiency virus (HIV). We evaluated 465 (114 male and 350 female) HIV-positive adults attending HIV clinics in Cape Town, South Africa. Demographic and clinical data were collected, and the participants were screened for current PTSD and traumatic event exposure using the Mini-International Neuropsychiatric Interview and the Life Events Checklist, respectively. The highest attributable risk for PTSD was derived from sexual assault (17.4%) and transport accidents (16.9%). Only sexual assault was significantly (p = 0.002) associated with current PTSD. Although sex had no effect on the prediction of current PTSD, HIVinfected men tended to experience more lifetime traumas than HIV-infected women, with the men having significantly higher rates of exposure than women to physical assault (p = 0.018) and assault with a weapon (p = 0.001). These data highlight the importance of considering trauma type in contributing to the burden of PTSD in HIV-infected adults.