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


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 · 4.94 Impact Factor
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    • "On the other hand the S allele may correlate with greater reactivity to stressful life events [34]; moreover it is well established that particular environmental factors can predict adverse behavioral outcomes such as depression, eating disorder and post-traumatic stress disorder [31], [32], [35], [75], [76], [77], [78], [79], [80]. However, individuals homozygous for the S allele are more likely to develop psychiatric symptoms when exposed to stressful life events, but least likely to do so when exposed to positive or neutral life events [81], [82], [83], [84], thus further confirming the role of the short allele as a factor heightening susceptibility to environmental factors [36], [37]. "
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    ABSTRACT: Reciprocity with primary caregivers affects subjects' adaptive abilities toward the construction of the most useful personal meaning organization (PMO) with respect to their developmental environment. Within cognitive theory the post-rationalist approach has outlined two basic categories of identity construction and of regulation of cognitive and emotional processes: the Outward and the Inward PMO. The presence of different, consistent clinical patterns in Inward and Outward subjects is paralleled by differences in cerebral activation during emotional tasks on fMRI and by different expression of some polymorphisms in serotonin pathways. Since several lines of evidence support a role for the 5-HTTLPR polymorphism in mediating individual susceptibility to environmental emotional stimuli, this study was conducted to investigate its influence in the development of the Inward/Outward PMO. PMO was assessed and the 5-HTTLPR polymorphism investigated in 124 healthy subjects who were subdivided into an Inward (n = 52) and an Outward (n = 72) group. Case-control comparisons of short allele (S) frequencies showed significant differences between Inwards and Outwards (p = 0.036, χ2 test; p = 0.026, exact test). Genotype frequencies were not significantly different although values slightly exceeded p≤0.05 (p = 0.056, χ2 test; p = 0.059, exact test). Analysis of the 5-HTTLPR genotypes according to the recessive inheritance model showed that the S/S genotype increased the likelihood of developing an Outward PMO (p = 0.0178, χ2 test; p = 0.0143, exact test; OR = 3.43, CI (95%) = 1.188–9.925). A logistic regression analysis confirmed the association between short allele and S/S genotypes with the Outward PMO also when gender and age were considered. However none of the differences remained significant after correction for multiple testing, even though using the recessive model they approach significance. Overall our data seem to suggest a putative genetic basis for interindividual differences in PMO development.
    PLoS ONE 12/2013; 8(12):e82192. DOI:10.1371/journal.pone.0082192 · 3.23 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(1). DOI:10.1016/j.jad.2013.09.018 · 3.38 Impact Factor
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