A Prospective Study of Serotonin Transporter Gene Promoter ( 5-HTT Gene Linked Polymorphic Region) and Intron 2 (Variable Number of Tandem Repeats) Polymorphisms as Predictors of Trauma Response to Mild Physical Injury
The aim of this study was to examine the effect of both promoter and intron polymorphisms of the serotonin transporter (5HTT) gene on posttraumatic stress disorder (PTSD) development. For this purpose, two polymorphisms of the 5-HTT gene, which are found in the promoter (5-HTT gene-linked polymorphic region) and second intron (variable number of tandem repeats) of the gene, were analyzed in 100 patients who were admitted to the Emergency Department after a mild physical trauma. None of the 5-HTT polymorphisms studied have an effect on PTSD development after a mild physical injury, but having L allele for 5-HTT gene-linked polymorphic region may cause milder hyperarousal symptoms in those patients who have developed PTSD.
"Though main effects of this polymorphism have been demonstrated (Lee et al., 2005; Thakur et al., 2009), most studies indicate that risk is associated with genotype (mainly S-allele carriers) and high trauma/stress (Kilpatrick et al., 2007; Grabe et al., 2009; Koenen et al., 2009; Xie et al., 2009, 2012; Kolassa et al., 2010b; Wang et al., 2011; Mercer et al., 2012). In contrast , several studies have reported no association (Mellman et al., 2009; Sayin et al., 2010). Complicating the issues of association studies with 5-HTTLPR is that the polymorphism has been found to be tri-allelic (L A / L G /S) in that a third functional allele (L G ) has been identified (Nakamura et al., 2000); thus, earlier association studies may not reflect the full range of genetic variation (Kenna et al., 2012). "
[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
New Insights into Anxiety Disorders, Edited by Federico Durbano, 03/2013: chapter Chapter 5 Alterations in the immune response, apoptosis and synaptic plasticity in posttraumatic stress disorder: molecular indicators and relation to clinical symptoms: pages 105-133; InTech.
"Differences in the direction of the allelic association have also been reported. Some studies reported association of the s allele with PTSD
[29,57], while others the l allele
. A meta-analysis would be highly recommended to derive more robust conclusions about the association of 5-HTTLPR with PTSD. "
[Show abstract][Hide abstract] ABSTRACT: Background
Posttraumatic stress disorder (PTSD) is a debilitating anxiety disorder. Surveys of the general population suggest that while 50-85% of Americans will experience a traumatic event in their lifetime, only 2-50% will develop PTSD. Why some individuals develop PTSD following trauma exposure while others remain resilient is a central question in the field of trauma research. For more than half a century, the role of genetic influences on PTSD has been considered as a potential vulnerability factor. However, despite the exponential growth of molecular genetic studies over the past decade, limited progress has been made in identifying true genetic variants for PTSD.
In an attempt to aid future genome wide association studies (GWAS), this paper presents a systematic review of 28 genetic association studies of PTSD. Inclusion criteria required that 1) all participants were exposed to Criterion A traumatic events, 2) polymorphisms of relevant genes were genotyped and assessed in relation to participants’ PTSD status, 3) quantitative methods were used, and 4) articles were published in English and in peer-reviewed journals. In the examination of these 28 studies, particular attention was given to variables related to trauma exposure (e.g. number of traumas, type of trauma).
Results indicated that most articles did not report on the GxE interaction in the context of PTSD or present data on the main effects of E despite having data available. Furthermore, some studies that did consider the GxE interaction had significant findings, underscoring the importance of examining how genotypes can modify the effect of trauma on PTSD. Additionally, results indicated that only a small number of genes continue to be studied and that there were marked differences in methodologies across studies, which subsequently limited robust conclusions.
As trauma exposure is a necessary condition for the PTSD diagnosis, this paper identifies gaps in the current literature as well as provides recommendations for how future GWAS studies can most effectively incorporate trauma exposure data in both the design and analysis phases of studies.
Biology of Mood and Anxiety Disorders 01/2013; 3(1):2. DOI:10.1186/2045-5380-3-2
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