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.
"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). "
[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 02/2014; 8:100. DOI:10.3389/fnhum.2014.00100 · 2.99 Impact Factor
"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). "
[Show abstract][Hide abstract] ABSTRACT: Post-traumatic stress disorder (PTSD) is increasingly recognized as both a disorder of enormous mental health and societal burden, but also as an anxiety disorder that may be particularly understandable from a scientific perspective. Specifically, PTSD can be conceptualized as a disorder of fear and stress dysregulation, and the neural circuitry underlying these pathways in both animals and humans are becoming increasingly well understood. Furthermore, PTSD is the only disorder in psychiatry in which the initiating factor, the trauma exposure, can be identified. Thus, the pathophysiology of the fear and stress response underlying PTSD can be examined and potentially interrupted. Twin studies have shown that the development of PTSD following a trauma is heritable, and that genetic risk factors may account for up to 30-40% of this heritability. A current goal is to understand the gene pathways that are associated with PTSD, and how those genes act on the fear/stress circuitry to mediate risk vs. resilience for PTSD. This review will examine gene pathways that have recently been analysed, primarily through candidate gene studies (including neuroimaging studies of candidate genes), in addition to genome-wide associations and the epigenetic regulation of PTSD. Future and on-going studies are utilizing larger and collaborative cohorts to identify novel gene candidates through genome-wide association and other powerful genomic approaches. Identification of PTSD biological pathways strengthens the hope of progress in the mechanistic understanding of a model psychiatric disorder and allows for the development of targeted treatments and interventions.
The International Journal of Neuropsychopharmacology 10/2013; 17(2):1-16. DOI:10.1017/S1461145713001090 · 4.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Post-traumatic stress disorder (PTSD) is a syndrome resulting from exposure to a severe traumatic event that poses threatened death or injury and produces intense fear and helplessness. The neural structures implicated in PTSD development belong to the limbic system, an important region for emotional processing. Brain-derived neurotrophic factor (BDNF) is a neurotrophin that serves as survival factor for selected populations of central nervous system (CNS) neurons and plays a role in the limbic system by regulating synaptic plasticity, memory processes and behavior. Impaired BDNF production in the brain can lead to a variety of CNS dysfunctions including symptoms associated with PTSD. However, so far fewer studies have investigated this neurotrophin in patients with PTSD. Furthermore, given the multiple role of BDNF in various CNS disorders, it cannot be excluded that traumatic events per se may influence neurotrophin levels, without a direct association to the PTSD syndrome. To elucidate these issues, in this study we analyzed BDNF serum levels in two groups of subjects: patients with trauma exposure who developed PTSD, and subjects with trauma exposure who did not develop PTSD. We found that BDNF serum levels were lower in PTSD patients as compared to related control subjects. Thus, these data suggest that BDNF might be involved in pathophysiology of PTSD and consequently therapeutic approaches aimed at restoring BDNF serum levels may be beneficial to this pathology.
Brain and Cognition 12/2013; 84(1):118-122. DOI:10.1016/j.bandc.2013.11.012 · 2.48 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.