Association Study of Trauma Load and<i>SLC6A4</i>Promoter Polymorphism in Posttraumatic Stress Disorder

Kolassa, Iris‐Tatjana; Ertl, Verena; Eckart, Cindy; Glöckner, Franka; Kolassa, Stephan; Papassotiropoulos, Andreas; Quervain, Dominique J.‐F. de; Elbert, Thomas

doi:10.4088/jcp.08m04787blu

Cited by 131 publications

(104 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This is consistent with previous studies showing that the S allele of 5-HTTLPR may be an independent risk factor for depression (Lee et al, 2005). The S allele is also positively correlated with post-traumatic stress disorder incidence rate (Kolassa et al, 2010). The L allele may be a protective factor and can reduce the incidence of depression (Grabe et al, 2009).…”

Section: Discussionsupporting

confidence: 92%

Relationship between 5-HTTLPR polymorphism and post-stroke depression

Guo¹,

Zhang²,

Mu³

et al. 2016

Genet. Mol. Res.

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 92%

Relationship between 5-HTTLPR polymorphism and post-stroke depression

Guo¹,

Zhang²,

Mu³

et al. 2016

Genet. Mol. Res.

View full text Add to dashboard Cite

“…transporter (SLC6A4) locus [34] and the catechol-Omethyltransferase (COMT) locus [35]. Although the prevalence of PTSD approached 100% when traumatic exposure reached extreme levels in both studies, those homozygous for the short SLC6A4 promoter allele showed 100% probability of PTSD independent of number of traumatic events [34]; and those homozygous for the Met COMT allele showed a high risk of PTSD even with small traumatic loads [35].…”

Section: Discussionmentioning

confidence: 92%

“…Our detection of a significant interaction between MAN2C1 methylation and participants' exposure to potentially traumatic events adds to a small but growing literature examining the joint and interacting ways in which molecular factors and cumulative traumatic burden may modify risk for PTSD. Recent work by Kolassa and colleagues [34,35] has focused on survivors of the Rwandan genocide and risk for PTSD in light of genetic variation at two distinct loci: the serotonin Table 2 of [19]. * * = p < 0.01 PTSD vs. control.…”

Section: Discussionmentioning

confidence: 99%

Gene Expression and Methylation Signatures ofMAN2C1are Associated with PTSD

et al. 2011

View full text Add to dashboard Cite

Abstract. As potential regulators of DNA accessibility and activity, epigenetic modifications offer a mechanism by which the environment can moderate the effects of genes. To date, however, there have been relatively few studies assessing epigenetic modifications associated with post-traumatic stress disorder (PTSD). Here we investigate PTSD-associated methylation differences in 33 genes previously shown to differ in whole blood-derived gene expression levels between those with vs. without the disorder. Drawing on DNA samples similarly obtained from whole blood in 100 individuals, 23 with and 77 without lifetime PTSD, we used methylation microarray data to assess whether these 33 candidate genes showed epigenetic signatures indicative of increased risk for, or resilience to, PTSD. Logistic regression analyses were performed to assess the main and interacting effects of candidate genes' methylation values and number of potentially traumatic events (PTEs), adjusting for age and other covariates. Results revealed that only one candidate gene -MAN2C1 -showed a significant methylation x PTE interaction, such that those with both higher MAN2C1 methylation and greater exposure to PTEs showed a marked increase in risk of lifetime PTSD (OR 4.35, 95% CI: 1.07, 17.77, p = 0.04). These results indicate that MAN2C1 methylation levels modify cumulative traumatic burden on risk of PTSD, and suggest that both gene expression and epigenetic changes at specific loci are associated with this disorder.

show abstract

“…Because the dopaminergic and adrenergic systems are also implicated in stress and fear biology, variation in dopamine regulating genes (e.g., dopamine β-hydroxylase, dopamine transporter and DRD2 genes) has been investigated in association with PTSD [22][23][24][25][26][27][28]. Variation in the serotonin transporter gene has been widely studied in association with PTSD [29][30][31] and in particular in the context of gene by environment studies [32][33][34] (see below for further discussion of this type of design). The interested reader is referred to recent reviews of genetic association studies in PTSD for further details [35,36].…”

Section: Gene Association Studies In Ptsdmentioning

confidence: 99%

“…Not only are levels of severity important with respect to a focal trauma, but cumulative effects of a lifetime of experiences. For example, whether the low expression allele in the promoter region of the serotonin transporter gene is associated with risk of PTSD depends on both individual-level trauma exposure severity [30] and macro-social context [33].…”

Section: Genes and Environment Jointly Predict Ptsdmentioning

confidence: 99%

The Role of Genes in Defining a Molecular Biology of PTSD

Yehuda

Koenen²,

Galea

et al. 2011

Disease Markers

View full text Add to dashboard Cite

Abstract. Because environmental exposure to trauma is the sine qua non for the development of Post Traumatic Stress Disorder (PTSD), the recent focus on genetic studies has been noteworthy. The main catalyst for such studies is the observation from epidemiological studies that not all trauma survivors develop this disorder. Furthermore, neuroendocrine findings suggest preexisting hormonal alterations that confer risk for PTSD. This paper presents the rationale for examining genetic factors in PTSD and trauma exposure, but suggests that studies of genotype may only present a limited picture of the molecular biology of this disorder. We describe the type of information that can be obtained from candidate gene and genomic studies that incorporate environmental factors in the design (i.e., gene -environment interaction and gene-environment correlation studies) and studies that capitalize on the idea that environment modifies gene expression, via epigenetic or other molecular mechanisms. The examination of epigenetic mechanisms in tandem with gene expression will help refine models that explain how PTSD risk, pathophysiology, and recovery is mediated by the environment. Since inherited genetic variation may also influence the extent of epigenetic or gene expression changes resulting from the environment, such studies should optimally be followed up by studies of genotype. If PTSD is a condition precipitated by environmental exposure, why examine genes?For at least two decades after the diagnosis of PTSD was established in 1980, it would have been unheard of to propose that genes might be involved in the etiology or pathogenesis of this condition. PTSD was initially defined as a disorder that resulted from exposure to a traumatic environmental event. The diagnosis was designed to describe universal effects of extreme stress that linger even after the stressor is removed. The theoretical contribution that this made to the biopsychosocial model of mental illness was the realization that the effects of an environmental event are not limited to initial exposure to the event, but can also persist for years and even decades. These long-term effects were conceptualized as being a function of the intensi- * Corresponding author. E-mail: Rachel.Yehuda@va.gov. ty and severity of the event that precipitated the initial symptoms.The implication of the PTSD diagnosis was that the adverse effects of exposure to chronic stressors (e.g., illness, family conflict, or financial pressures) could be alleviated or even eliminated if the challenge to the person was removed (and hence were not precipitants of PTSD). In contrast, the effects of exposure to lifethreatening events like interpersonal violence, combat, and accidents that caused intense fear, helplessness and horror were not only persistent, but were of a specific and universal nature. The basic phenomenology of PTSD asserted that following trauma exposure, the survivor experiences unwanted, uncontrollable memories of the event that generate physical and emotional responses resem...

show abstract

Association Study of Trauma Load andSLC6A4Promoter Polymorphism in Posttraumatic Stress Disorder

Cited by 131 publications

References 36 publications

Relationship between 5-HTTLPR polymorphism and post-stroke depression

Relationship between 5-HTTLPR polymorphism and post-stroke depression

Gene Expression and Methylation Signatures ofMAN2C1are Associated with PTSD

The Role of Genes in Defining a Molecular Biology of PTSD

Contact Info

Product

Resources

About