Epigenetic Aspects of Posttraumatic Stress Disorder

Max Planck Institute of Psychiatry, Munich, Germany.
Disease markers (Impact Factor: 1.56). 04/2011; 30(2-3):77-87. DOI: 10.3233/DMA-2011-0749
Source: PubMed


Development of psychiatric diseases such as posttraumatic stress disorder (PTSD) invokes, as with most complex diseases, both genetic and environmental factors. The era of genome-wide high throughput technologies has sparked the initiation of genotype screenings in large cohorts of diseased and control individuals, but had limited success in identification of disease causing genetic variants. It has become evident that these efforts at the genomic level need to be complemented with endeavours in elucidating the proteome, transcriptome and epigenetic profiles. Epigenetics is attractive in particular because there is accumulating evidence that the lasting impact of adverse life events is reflected in certain covalent modifications of the chromatin.
In this review, we outline the characteristics of PTSD as a stress-related disease and survey recent developments revealing epigenetic aspects of stress-related disorders in general. There is also increasing direct evidence for gene programming and epigenetic components in PTSD. Finally, we discuss treatment options in the light of recent discoveries of epigenetic mechanisms of psychotropic drugs.

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    • " ; Cicchetti and Toth , 2009 ) , such as anx - iety symptoms and externalizing problems ( e . g . , Linares et al . , 2001 ; Graham - Bermann et al . , 2009 ) , lends itself to questions regarding the mechanisms underlying this inter - generational transmission process . Among the biological ( e . g . , epigenetics ; Yehuda and Bierer , 2009 ; see Schmidt et al . , 2011 for a review ) , psychological , and environmen - tal mechanisms that have been proposed ( Leen - Feldner et al . , 2013 ; Rijlaarsdam et al . , 2014 ) , a growing body of neuroendocrine research supports the postulation that altered hypothalamic—pituitary—adrenal ( HPA ) axis func - tioning plays a role in this transmission ( Yehuda et"
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    ABSTRACT: Parental Posttraumatic Stress Disorder (PTSD), particularly maternal PTSD, confers risk for stress-related psychopathology among offspring. Altered hypothalamic-pituitary-adrenal (HPA) axis functioning is one mechanism proposed to explain transmission of this intergenerational risk. Investigation of this mechanism has been largely limited to general stress response (e.g., diurnal cortisol), rather than reactivity in response to an acute stressor. We examined cortisol reactivity in response to a laboratory stressor among offspring of mothers with a lifetime diagnosis of PTSD (n=36) and age- and gender- matched control offspring of mothers without PTSD (n=36). Youth (67% girls; mean age=11.4, SD=2.6) participated in a developmentally sensitive laboratory stressor and had salivary cortisol assessed five times (one pre-stress, one immediate post-stress, and three recovery measures, spaced 15min apart). Results were consistent with the hypothesis that offspring of mothers with PTSD would exhibit a dysregulated, blunted cortisol reactivity profile, and control offspring would display the expected adaptive peak in cortisol response to challenge profile. Findings were maintained after controlling for youth traumatic event history, physical anxiety symptoms, and depression, as well as maternal depression. This finding contributes to the existing literature indicating that attenuated HPA axis functioning, inclusive of hyposecretion of cortisol in response to acute stress, is robust among youth of mothers with PTSD. Future research is warranted in elucidating cortisol reactivity as a link between maternal PTSD and stress-related psychopathology vulnerability among offspring. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Psychoneuroendocrinology 01/2015; 53C:170-178. DOI:10.1016/j.psyneuen.2015.01.001 · 4.94 Impact Factor
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    • "The probability to develop PTSD depends on individual risk and resilience factors and increases with the number of traumatic events experienced [4] as well as with the stress intensity of the traumatic incidents [5]. There is much evidence that social factors like the extent of familiar support [6], psychological factors such as cognitive reappraisal and optimism [7], and biological factors like epigenetic markers [8], single nucleotide polymorphisms (SNPs) [9], endocrine factors [10], and neurotransmitter systems [11] modulate PTSD susceptibility, progression of PTSD, and probably also the response to PTSD treatment. PTSD susceptibility biomarkers would be especially useful for prevention in professions at high risk for trauma exposure like combat soldiers and firefighters. "
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    ABSTRACT: PTSD can develop in the aftermath of traumatic incidents like combat, sexual abuse, or life threatening accidents. Unfortunately, there are still no biomarkers for this debilitating anxiety disorder in clinical use. Anyhow, there are numerous studies describing potential PTSD biomarkers, some of which might progress to the point of practical use in the future. Here, we outline and comment on some of the most prominent findings on potential imaging, psychological, endocrine, and molecular PTSD biomarkers and classify them into risk, disease, and therapy markers. Since for most of these potential PTSD markers a causal role in PTSD has been demonstrated or at least postulated, this review also gives an overview on the current state of research on PTSD pathobiology.
    Disease markers 07/2013; 35(1):43-54. DOI:10.1155/2013/835876 · 1.56 Impact Factor
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    • "Higher methylation of MAN2C1, a gene that encodes α-mannosidase, was shown to interact with greater exposure to potentially traumatic events to predict an increased risk of lifetime PTSD (Uddin et al., 2011). A number of epigenetic studies in animal models and humans investigating the association between epigenetic changes and risk for maladaptive stress responses and mental illnesses have recently been published (Radley et al., 2011; Schmidt et al., 2011; Murgatroyd and Spengler, 2012; Rusiecki et al., 2012). "
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    ABSTRACT: Resilience is the ability to adapt successfully in the face of stress and adversity. Stressful life events, trauma, and chronic adversity can have a substantial impact on brain function and structure, and can result in the development of posttraumatic stress disorder (PTSD), depression and other psychiatric disorders. However, most individuals do not develop such illnesses after experiencing stressful life events, and are thus thought to be resilient. Resilience as successful adaptation relies on effective responses to environmental challenges and ultimate resistance to the deleterious effects of stress, therefore a greater understanding of the factors that promote such effects is of great relevance. This review focuses on recent findings regarding genetic, epigenetic, developmental, psychosocial, and neurochemical factors that are considered essential contributors to the development of resilience. Neural circuits and pathways involved in mediating resilience are also discussed. The growing understanding of resilience factors will hopefully lead to the development of new pharmacological and psychological interventions for enhancing resilience and mitigating the untoward consequences.
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