Gene-environment interaction in posttraumatic stress disorder: An update

Department of Society, Human Development, and Health, Harvard School of Public Health, Boston, MA 02115, USA.
Journal of Traumatic Stress (Impact Factor: 2.72). 10/2009; 22(5):416-26. DOI: 10.1002/jts.20435
Source: PubMed

ABSTRACT The authors provide a detailed review of the extant gene-environment interaction (GxE) research in the etiology of posttraumatic stress disorder (PTSD). They begin with a discussion of why PTSD is uniquely fitting for the innovative framework of GxE methodology, followed by a review of the heritability and main effect molecular genetics studies of PTSD. Next, they discuss the six GxE investigations to date on PTSD. They end with a discussion of future directions and significance of this research, with an emphasis on the expansion of psychosocial factors that may be fitting environmental variables for inclusion in this new research area. The authors posit that GxE research is vital to elucidating risk and resilience following exposure to a potentially traumatic event.

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Available from: Nicole R Nugent, Oct 09, 2014
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    • "Yet, there is an apparent paradox; i.e., the observation that peripheral blood mononuclear cells (PBMCs) from PTSD patients show increased sensitivity to glucocorticoid-mediated suppression of an insitu inflammatory response (van Zuiden et al., 2012b). There is considerable evidence that genetic effects, environmental influences, and their interaction play a role in the development of PTSD (Afifi et al., 2010; Koenen et al., 2009; True et al., 1993). There is a well-established body of clinical literature supporting a link between early life events, previous exposure to traumatic stress, and other psychosocial factors with the development of PTSD (Brewin et al., 2000; Ozer et al., 2003; DiGangi et al., 2013). "
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    ABSTRACT: The etiology of post-traumatic stress disorder (PTSD) likely involves the interaction of numerous genes and environmental factors. Similarly, gene-expression levels in peripheral blood are influenced by both genes and environment, and expression levels of many genes show good correspondence between peripheral blood and brain tissues. In that context, this pilot study sought to test the following hypotheses: (1) post-trauma expression levels of a gene subset in peripheral blood would differ between Marines with and without PTSD; (2) a diagnostic biomarker panel of PTSD among high-risk individuals could be developed based on gene-expression in readily assessable peripheral blood cells; and (3) a diagnostic panel based on expression of individual exons would surpass the accuracy of a model based on expression of full-length gene transcripts. Gene-expression levels in peripheral blood samples from 50 U.S. Marines (25 PTSD cases and 25 non-PTSD comparison subjects) were determined by microarray following their return from deployment to war-zones in Iraq or Afghanistan. The original sample was carved into training and test subsets for construction of support vector machine classifiers. The panel of peripheral blood biomarkers achieved 80% prediction accuracy in the test subset based on the expression of just two full-length transcripts (GSTM1 and GSTM2). A biomarker panel based on 20 exons attained an improved 90% accuracy in the test subset. Though further refinement and replication of these biomarker profiles are required, these preliminary results provide proof-of-principle for the diagnostic utility of blood-based mRNA-expression in PTSD among trauma-exposed individuals.
    Psychoneuroendocrinology 09/2014; 51. DOI:10.1016/j.psyneuen.2014.09.024 · 5.59 Impact Factor
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    • "Although less is known about PTG, recent studies suggest that upwards of 50% of survivors of natural disasters experience some degree of PTG (Tang, 2006; Xu and Liao, 2011; Yu et al., 2010), with PTG being more common among older adults, non-Hispanic Blacks, and those exposed to a greater number of stressors (Lowe et al., 2013). Although genetic factors contribute to variation in response to trauma (Dunn et al., 2011; Koenen et al., 2009a), only a handful of studies have examined gene–environment interaction (GxE) as a determinant of PTSD and anxiety-related outcomes in the context of a natural disaster (Kilpatrick et al., 2007; Koenen et al., 2009b; Amstadter et al., 2009; Pietrzak et al., 2013). Kilpatrick and colleagues found a three-way interaction between 5-HTTLPR genotype, hurricane exposure, and social support, with the highest levels of PTSD detected among those with the short/short (s/s) genotype, low social support, and high hurricane exposure (Kilpatrick et al., 2007). "
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    ABSTRACT: There is considerable variation in psychological reactions to natural disasters, with responses ranging from relatively mild and transitory symptoms to severe and persistent posttraumatic stress (PTS). Some survivors also report post-traumatic growth (PTG), or positive psychological changes due to the experience and processing of the disaster and its aftermath. Gene-environment interaction (GxE) studies could offer new insight into the factors underlying variability in post-disaster psychological responses. However, few studies have explored GxE in a disaster context. We examined whether ten common variants in seven genes (BDNF, CACNA1C, CRHR1, FKBP5, OXTR, RGS2, SLC6A4) modified associations between Hurricane Katrina exposure and PTS and PTG. Data were from a prospective study of 205 low-income non-Hispanic Black parents residing in New Orleans prior to and following Hurricane Katrina. We found a significant association (after correction) between RGS2 (rs4606; p=0.0044) and PTG, which was mainly driven by a cross-over GxE (p=0.006), rather than a main genetic effect (p=0.071). The G (minor allele) was associated with lower PTG scores for low levels of Hurricane exposure and higher PTG scores for moderate and high levels of exposure. We also found a nominally significant association between variation in FKBP5 (rs1306780, p=0.0113) and PTG, though this result did not survive correction for multiple testing. Although the inclusion of low-income non-Hispanic Black parents allowed us to examine GxE among a highly vulnerable group, our findings may not generalize to other populations or groups experiencing other natural disasters. Moreover, not all participants invited to participate in the genetic study provided saliva. To our knowledge, this is the first study to identify GxE in the context of post-traumatic growth. Future studies are needed to clarify the role of GxE in PTS and PTG and post-disaster psychological responses, especially among vulnerable populations.
    Journal of Affective Disorders 10/2013; 152. DOI:10.1016/j.jad.2013.09.018 · 3.71 Impact Factor
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    • "Therefore, further molecular genetic studies focusing on identifying possible specific loci for PTSD are needed. As PTSD's diagnosis requires exposure to an environmental pathogen and its development appears to be mediated by both genetic and environmental factors, a gene– environment interaction (G Â E) approach has been widely proposed for genetic investigations of PTSD (Koenen et al., 2009a; Norrholm and Ressler, 2009). Pituitary adenylate cyclase-activating polypeptide (PACAP) and its selective PAC1 receptor are richly localized in hypothalamic and limbic structures and regulate the physiological and psychological responses to stress across species (Cho et al., 2012; Lehmann et al., in press; Hashimoto et al., 2011). "
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    ABSTRACT: BACKGROUND: Genetic factors are important in the development of posttraumatic stress disorder (PTSD) following exposure to traumatic events. However, the molecular genetic underpinnings of this disorder remain largely unresolved. The present study investigated the association between ADCYAP1R1 rs2267735 genotype and PTSD symptoms in a highly traumatized sample of Chinese adults. METHODS: Participants included 326 victims who experienced 2008 Wenchuan earthquake and lost their children during the disaster. PTSD symptoms were assessed with the PTSD Checklist (PCL). The ADCYAP1R1 rs2267735 SNP was genotyped with the Sequenom iPlex chemistries and the MassARRAY system. RESULTS: The results indicated that although the rs2267735 'CC' genotype was not associated with total PTSD symptoms, it could significantly predict severity of PTSD's emotional numbing symptoms inwomen. LIMITATIONS: A relatively small sample exposed to specific traumatic events was used, and PTSD was assessed using a self-reported instrument. CONCLUSIONS: The findings suggest that the PACAP-PAC1 receptor pathway may play an important role in female human responses to traumatic stress, and carry implications for better understanding and treating of posttraumatic psychopathology.
    Journal of Affective Disorders 02/2013; 150(1). DOI:10.1016/j.jad.2013.01.010 · 3.71 Impact Factor
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