Genetics of anxiety and trauma-related disorders

Norrholm, Seth D.; Ressler, Kerry J.

doi:10.1016/j.neuroscience.2009.06.036

Cited by 88 publications

(50 citation statements)

References 142 publications

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“…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%

The Role of Genes in Defining a Molecular Biology of PTSD

Yehuda

Koenen²,

Galea

et al. 2011

Disease Markers

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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...

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Section: Gene Association Studies In Ptsdmentioning

confidence: 99%

The Role of Genes in Defining a Molecular Biology of PTSD

Yehuda

Koenen²,

Galea

et al. 2011

Disease Markers

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show abstract

“…Until recently, the genetic contribution to PTSD has been investigated largely via candidate gene association studies (reviewed in Almli et al, 2014;Amstadter et al, 2009;Norrholm and Ressler, 2009). Most research has focused on: (1) the hypothalamic-pituitary-adrenal (HPA) axis, (2) the ascending brainstem locus coeruleus noradrenergic system, and (3) the limbic amygdalar frontal pathway mediating fear processing.…”

Section: Introductionmentioning

confidence: 99%

Genomic predictors of combat stress vulnerability and resilience in U.S. Marines: A genome-wide association study across multiple ancestries implicates PRTFDC1 as a potential PTSD gene

Nievergelt

Maihofer

Mustapić

et al. 2015

Psychoneuroendocrinology

151

120

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“…Besides gender differences, there are some risk factors known to be involved in PTSD development, such as biological, psychological vulnerabilities and social factors. There is a small or no evidence regarding genetic factor for the PTSD development [6]. In opposite, Vietnam veterans study showed that psychological stress, such as family instability, was found to be a risk factor for the development of PTSD [7].…”

Section: Ptsd Causesmentioning

confidence: 98%