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Association of CRHR1 variants and posttraumatic stress symptoms in hurricane exposed adults.

ABSTRACT: Posttraumatic stress disorder (PTSD) is a moderately heritable anxiety disorder that may develop after exposure to trauma. However, only few genetic variants that relate to PTSD have been studied. This study examined the relationship between 12 single nucleotide polymorphisms (SNPs) in the corticotropin-releasing hormone receptor 1 gene (CRHR1) and post-disaster PTSD symptoms and diagnosis in adults exposed to 2004 Florida hurricanes. CRHR1 regulates the hypothalamic-pituitary-adrenal (HPA) axis; dysregulation of the HPA axis is characteristic of stress phenotypes. Final analyses were conducted in the European-American (EA) subsample (n=564) due to population stratification. After correction for multiple testing, rs12938031 and rs4792887 remained associated with post-hurricane PTSD symptoms. Additionally, rs12938031 was associated with post-hurricane diagnosis of PTSD. This study is the first to examine CRHR1 in relation to PTSD in adults, and provides evidence for the importance of CRHR1 variation in the etiology of PTSD. Although results are preliminary and require replication, they justify follow-up efforts to characterize how this gene relates to PTSD.

SUBMITTER: White S

PROVIDER: S-EPMC4182958 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Association of CRHR1 variants and posttraumatic stress symptoms in hurricane exposed adults.

White Simone S Acierno Ron R Ruggiero Kenneth J KJ Koenen Karestan C KC Kilpatrick Dean G DG Galea Sandro S Gelernter Joel J Williamson Vernell V McMichael Omari O Vladimirov Vladimir I VI Amstadter Ananda B AB

Journal of anxiety disorders 20130827 7

Posttraumatic stress disorder (PTSD) is a moderately heritable anxiety disorder that may develop after exposure to trauma. However, only few genetic variants that relate to PTSD have been studied. This study examined the relationship between 12 single nucleotide polymorphisms (SNPs) in the corticotropin-releasing hormone receptor 1 gene (CRHR1) and post-disaster PTSD symptoms and diagnosis in adults exposed to 2004 Florida hurricanes. CRHR1 regulates the hypothalamic-pituitary-adrenal (HPA) axis ...[more]

PMID: 24077033

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Project description:ContextIn addition to trauma exposure, other factors contribute to risk for development of posttraumatic stress disorder (PTSD) in adulthood. Both genetic and environmental factors are contributory, with child abuse providing significant risk liability.ObjectiveTo increase understanding of genetic and environmental risk factors as well as their interaction in the development of PTSD by gene x environment interactions of child abuse, level of non-child abuse trauma exposure, and genetic polymorphisms at the stress-related gene FKBP5.Design, setting, and participantsA cross-sectional study examining genetic and psychological risk factors in 900 nonpsychiatric clinic patients (762 included for all genotype studies) with significant levels of childhood abuse as well as non-child abuse trauma using a verbally presented survey combined with single-nucleotide polymorphism (SNP) genotyping. Participants were primarily urban, low-income, black (>95%) men and women seeking care in the general medical care and obstetrics-gynecology clinics of an urban public hospital in Atlanta, Georgia, between 2005 and 2007.Main outcome measuresSeverity of adult PTSD symptomatology, measured with the modified PTSD Symptom Scale, non-child abuse (primarily adult) trauma exposure and child abuse measured using the traumatic events inventory and 8 SNPs spanning the FKBP5 locus.ResultsLevel of child abuse and non-child abuse trauma each separately predicted level of adult PTSD symptomatology (mean [SD], PTSD Symptom Scale for no child abuse, 8.03 [10.48] vs > or =2 types of abuse, 20.93 [14.32]; and for no non-child abuse trauma, 3.58 [6.27] vs > or =4 types, 16.74 [12.90]; P < .001). Although FKBP5 SNPs did not directly predict PTSD symptom outcome or interact with level of non-child abuse trauma to predict PTSD symptom severity, 4 SNPs in the FKBP5 locus significantly interacted (rs9296158, rs3800373, rs1360780, and rs9470080; minimum P = .0004) with the severity of child abuse to predict level of adult PTSD symptoms after correcting for multiple testing. This gene x environment interaction remained significant when controlling for depression severity scores, age, sex, levels of non-child abuse trauma exposure, and genetic ancestry. This genetic interaction was also paralleled by FKBP5 genotype-dependent and PTSD-dependent effects on glucocorticoid receptor sensitivity, measured by the dexamethasone suppression test.ConclusionsFour SNPs of the FKBP5 gene interacted with severity of child abuse as a predictor of adult PTSD symptoms. There were no main effects of the SNPs on PTSD symptoms and no significant genetic interactions with level of non-child abuse trauma as predictor of adult PTSD symptoms, suggesting a potential gene-childhood environment interaction for adult PTSD.

Project description:BackgroundThe 5th revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) construes PTSD symptoms into 4 clusters (intrusion, avoidance, negative alterations in cognitions and mood, alterations in arousal and reactivity; Model 1). However, recent literature has shown that this symptom structure does not best represent PTSD. Unfortunately, the findings of studies investigating the proposed alternative models are from consensus. Adding to the complexity of the issue of symptom-grouping models is the identification of specific and non-specific symptoms of PTSD. The present study aims to address these gaps by identifying the best-fitting PTSD model and subsequently examining what symptoms are considered specific and non-specific to PTSD in adolescent-survivors of armed political conflict and violence.MethodsThe study utilized a sample of 641 adolescent victim survivors. We conducted CFA analyses and compared nested models through the scaled χ2 difference test, while comparison of non-nested models was done using the Bayesian information criterion (BIC). The best-fitted model was used in the consequent analysis, where we statistically controlled for the effect of non-specific psychological distress on PTSD by comparing the factor loadings and factor correlations before and after accounting for distress using the Aroian z-test.ResultsThe results provide support for the 7-factor hybrid model of PTSD over other proposed models for the current sample. Moreover, the data reveal that only 7 items could be construed as core symptoms, while the rest of the symptoms can be considered non-PTSD specific.ConclusionsOverall, the findings provide support for the validity of the hybrid PTSD model among political conflict-exposed adolescents. The results also show that the DSM-5 PTSD has both specific and non-specific features in the present sample of conflict-exposed adolescents. This has potential implications for theory, practice, and treatment of the disorder.

Dataset Information

Association of CRHR1 variants and posttraumatic stress symptoms in hurricane exposed adults.

Publications

Association of CRHR1 variants and posttraumatic stress symptoms in hurricane exposed adults.

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