Dataset Information

RORA and posttraumatic stress trajectories: main effects and interactions with childhood physical abuse history.

ABSTRACT:

Background

Longitudinal studies of posttraumatic stress (PTS) have documented environmental factors as predictors of trajectories of higher, versus lower, symptoms, among them experiences of childhood physical abuse. Although it is now well-accepted that genes and environments jointly shape the risk of PTS, no published studies have investigated genes, or gene-by-environment interactions (GxEs), as predictors of PTS trajectories. The purpose of this study was to fill this gap.

Methods and materials

We examined associations between variants of the retinoid-related orphan receptor alpha (RORA) gene and trajectory membership among a sample of predominantly non-Hispanic Black urban adults (N = 473). The RORA gene was selected based on its association with posttraumatic stress disorder (PTSD) in the first PTSD genome wide association study. Additionally, we explored GxEs between RORA variants and childhood physical abuse history.

Results

We found that the minor allele of the RORA SNP rs893290 was a significant predictor of membership in a trajectory of consistently high PTS, relatively to a trajectory of consistently low PTS. Additionally, the GxE of rs893290 with childhood physical abuse was significant. Decomposition of the interaction showed that minor allele frequency was more strongly associated with membership in consistently high or decreasing PTS trajectories, relative to a consistently low PTS trajectory, among participants with higher levels of childhood physical abuse.

Conclusion

The results of the study provide preliminary evidence that variation in the RORA gene is associated with membership in trajectories of higher PTS and that these associations are stronger among persons exposed to childhood physical abuse. Replication and analysis of functional data are needed to further our understanding of how RORA relates to PTS trajectories.

SUBMITTER: Lowe SR

PROVIDER: S-EPMC4356849 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:The aims of this review are (i) to summarize and evaluate current knowledge on the association between childhood sexual abuse (CSA) and posttraumatic stress disorder (PTSD) in pregnant and postpartum women, (ii) to provide suggestions for future research on this topic, and (iii) to highlight some clinical implications. Relevant publications were identified through literature searches of four databases (PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, and PsycARTICLES) using keywords such as "child abuse," "posttraumatic stress," "pregnancy," and "postpartum". Five studies were included in this review. Findings across all studies were consistent with higher prevalence of PTSD diagnosis or symptomatology among women with history of CSA. However, only findings from two studies were statistically significant. One study observed higher overall PTSD scores in women with CSA history compared to women with non-CSA trauma history or no trauma history during pregnancy (mean?±?SD 1.47 (0.51) vs. 1.33 (0.41) vs. 1.22 (0.29), p?<?0.001), at 2 months postpartum (mean?±?SD 1.43 (0.49) vs. 1.26 (0.38) vs. 1.19 (0.35), p?<?0.001), and at 6 months postpartum (mean?±?SD 1.36 (1.43) vs. 1.20 (0.33) vs. 1.14 (0.27), p?<?0.001). Another study observed that the prevalence of PTSD during pregnancy was 4.1 % in women with no history of physical or sexual abuse, 11.4 % in women with adult physical or sexual abuse history, 16.0 % in women with childhood physical or sexual abuse history, and 39.0 % in women exposed to both childhood and adult physical or sexual abuse (p?<?0.001); in a subsequent analysis, the investigators reported that pregnant women with PTSD had over 5-fold odds of having a history of childhood completed rape compared to counterparts without PTSD (OR = 5.3, 95 % CI 3.2, 8.7). Overall, available evidence suggests positive associations of CSA with clinical PTSD or PTSD symptomatology among pregnant and postpartum women.

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:ImportanceDespite the high prevalence, evidence-based treatments for abuse-related posttraumatic stress disorder (PTSD) in adolescents have rarely been studied.ObjectiveTo examine whether developmentally adapted cognitive processing therapy (D-CPT) is more effective than a wait-list condition with treatment advice (WL/TA) among adolescents with PTSD related to childhood abuse.Design, setting, and participantsThis rater-blinded, multicenter, randomized clinical trial (stratified by center) enrolled treatment-seeking adolescents and young adults (aged 14-21 years) with childhood abuse-related PTSD at 3 university outpatient clinics in Germany from July 2013 to June 2015, with the last follow-up interview conducted by May 2016. Of 194 patients, 88 were eligible for randomization.InterventionsParticipants received D-CPT or WL/TA. Cognitive processing therapy was enhanced by a motivational and alliance-building phase, by including emotion regulation and consideration of typical developmental tasks, and by higher session frequency in the trauma-focused core CPT phase. In WL/TA, participants received treatment advice with respective recommendations of clinicians and were offered D-CPT after 7 months.Main outcomes and measuresAll outcomes were assessed before treatment (baseline), approximately 8 weeks after the start of treatment, after the end of treatment (posttreatment), and at the 3-month follow-up. The primary outcome, PTSD symptom severity, was assessed in clinical interview (Clinician-Administered PTSD Scale for Children and Adolescents for DSM-IV [CAPS-CA]). Secondary outcomes were self-reported PTSD severity, depression, borderline symptoms, behavior problems, and dissociation.ResultsThe 88 participants (75 [85%] female) had a mean age of 18.1 years (95% CI, 17.6-18.6 years). In the intention-to-treat analysis, the 44 participants receiving D-CPT (39 [89%] female) demonstrated greater improvement than the 44 WL/TA participants (36 [82%] female) in terms of PTSD severity (mean CAPS-CA scores, 24.7 [95% CI, 16.6-32.7] vs 47.5 [95% CI, 37.9-57.1]; Hedges g = 0.90). This difference was maintained through the follow-up (mean CAPS-CA scores, 25.9 [95% CI, 16.2-35.6] vs 47.3 [95% CI, 37.8-56.8]; Hedges g = 0.80). Treatment success was greatest during the trauma-focused core phase. The D-CPT participants also showed greater and stable improvement in all secondary outcomes, with between-groups effect sizes ranging from 0.65 to 1.08 at the posttreatment assessment (eg, for borderline symptoms, 14.1 [95% CI, 8.0-20.2] vs 32.0 [95% CI, 23.8-40.2]; Hedges g = 0.91).Conclusions and relevanceAdolescents and young adults with abuse-related PTSD benefited more from D-CPT than from WL/TA. Treatment success was stable at the follow-up and generalized to borderline symptoms and other comorbidities.Trial registrationGerman Clinical Trials Register identifier: DRKS00004787.