5-HTTLPR and DISC1 risk genotypes for elevated PTSD symptoms in US military veterans.
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ABSTRACT:
SUBMITTER: Young KA
PROVIDER: S-EPMC5269485 | biostudies-literature | 2017 Feb
REPOSITORIES: biostudies-literature
Publications
5-HTTLPR and DISC1 risk genotypes for elevated PTSD symptoms in US military veterans.
Young Keith A KA Morissette Sandra B SB Jamroz Robert R Meyer Eric C EC Stanford Matthew S MS Wan Li L Kimbrel Nathan A NA
World psychiatry : official journal of the World Psychiatric Association (WPA) 20170201 1
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Project description:Post-traumatic stress disorder (PTSD), a complex and chronic disorder caused by exposure to a traumatic event, is a common psychological result of current military operations. It causes substantial distress and interferes with personal and social functioning. Consequently, identifying the risk factors that make military personnel and veterans more likely to experience PTSD is of academic, clinical, and social importance. Four electronic databases (PubMed, Embase, Web of Science, and PsycINFO) were used to search for observational studies (cross-sectional, retrospective, and cohort studies) about PTSD after deployment to combat areas. The literature search, study selection, and data extraction were conducted by two of the authors independently. Thirty-two articles were included in this study. Summary estimates were obtained using random-effects models. Subgroup analyses, sensitivity analyses, and publication bias tests were performed. The prevalence of combat-related PTSD ranged from 1.09% to 34.84%. A total of 18 significant predictors of PTSD among military personnel and veterans were found. Risk factors stemming from before the trauma include female gender, ethnic minority status, low education, non-officer ranks, army service, combat specialization, high numbers of deployments, longer cumulative length of deployments, more adverse life events, prior trauma exposure, and prior psychological problems. Various aspects of the trauma period also constituted risk factors. These include increased combat exposure, discharging a weapon, witnessing someone being wounded or killed, severe trauma, and deployment-related stressors. Lastly, lack of post-deployment support during the post-trauma period also increased the risk of PTSD. The current analysis provides evidence of risk factors for combat-related PTSD in military personnel and veterans. More research is needed to determine how these variables interact and how to best protect against susceptibility to PTSD.
| S-EPMC4368749 | biostudies-literature
Project description:Epigenetic alterations in DNA methylation might mediate gene expression effects of trauma underlying PTSD symptoms, or effects of PTSD on related health problems. PTSD is associated with all-cause morbidity and premature mortality, suggesting accelerated biological aging. We measured genome-wide DNA methylation (Illumina MethylationEPIC BeadChip) in whole blood in a treatment study for combat-related PTSD - "PROGrESS", a multisite RCT comparing sertraline plus enhanced medication management (SERT + EMM), prolonged exposure (PE) therapy plus placebo (PE + PLB), and the combination (SERT + PE). DNA methylation was measured in 140 US military veterans who served in Iraq and/or Afghanistan (112 current PTSD cases enrolled in a PTSD treatment study and 28 veterans without PTSD history controls), and also 59 non-trauma exposed controls at baseline posttreatment (24 weeks after baseline). Increased DNA methylation GrimAge acceleration (p = 8.8e-09) was observed in patients with PTSD compared to a pooled control group (trauma exposed and non-trauma exposed), suggesting a higher risk of premature mortality in those with PTSD. There was no difference in GrimAge acceleration between combat trauma and non-trauma exposed controls. No treatment-related changes in GrimAge acceleration were found in within-subject comparisons of PTSD patients pre- to post-treatment.
| S-EPMC10066228 | biostudies-literature
Project description:Research has demonstrated that the impact of the coronavirus 2019 (COVID-19) pandemic on the mental health of United States (U.S.) veterans was less negative than originally anticipated. However, U.S. veterans are susceptible to exacerbation of post-traumatic stress disorder (PTSD) symptomology in late life. The aims of this study were to examine the extent to which older U.S. veterans experienced an exacerbation of PTSD symptoms during the COVID-19 pandemic, and to identify pre- and peri-pandemic factors that conferred risk for symptom exacerbation. Participants were U.S. military veterans aged 60 and older who completed three waves of the 2019-2022 National Health and Resilience in Veterans Study (NHRVS) (n=1858). PTSD symptoms were measured at all waves using the PTSD Checklist for DSM-5, and a latent growth mixture model was conducted to compute latent slopes of change of PTSD symptoms over the 3-year period. 159 (8.3%) participants experienced a worsening of PTSD symptomology over the pandemic period. Factors related to PTSD exacerbation were incident trauma exposure between Waves 1 and 2, more medical conditions with onset prior to the pandemic, and peri-pandemic social restriction stress. Number of incident traumas moderated the relationship between both number of pre-pandemic medical conditions and pre-pandemic social connectedness, and exacerbated PTSD symptoms. These results suggest that the pandemic did not confer additional risk for PTSD exacerbation than would be expected over a 3-year period for older veterans. Those who experience incident trauma exposure should be monitored for symptom exacerbation.
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Project description:ObjectivesTo examine whether attachment style moderates the relationship between polygenic risk scores (PRS) for posttraumatic stress disorder (PTSD) re-experiencing (PTSDREX) symptoms and the severity of and positive screen for traumatic loss-related PTSD.MethodsData were analysed from 631 US veterans who endorsed 'unexpected death of a loved one' as their 'worst' traumatic event. Multivariable models evaluated the association between PRS for PTSDREX, attachment style, and their interaction in predicting severity and positive screen for PTSD. A gene enrichment analysis was conducted to identify possible molecular mechanisms underlying the association between PTSDREX PRS and PTSD.ResultsPTSDREX PRS (β = 0.17; odds ratio [OR] = 1.85), attachment style (β= -0.33; OR = 0.14), and PTSDREX PRS × attachment style interaction (β= -0.12; OR = 0.53) were significant predictors of the severity and positive screen for PTSD. The most significant gene set detected was the gene ontology (GO) cellular component podosome set (GO:0002102, p < 3.95 × 10-5).ConclusionsHaving a secure attachment style may help mitigate polygenic risk for developing traumatic loss-related PTSD in US veterans. Podosomes, which are implicated in inflammatory and neuroplasticity processes, may contribute to the genetic liability to developing loss-related PTSD. Psychological treatments targeting attachment security may help mitigate increased polygenic risk for loss-related PTSD in this population.
| S-EPMC8925016 | biostudies-literature
Project description:BackgroundPosttraumatic stress disorder (PTSD) and traumatic brain injury (TBI) are associated with self-reported problems with cognition as well as risk for Alzheimer's disease and related dementias (ADRD). Overlapping symptom profiles observed in cognitive disorders, psychiatric disorders, and environmental exposures (e.g., head injury) can complicate the detection of early signs of ADRD. The interplay between PTSD, head injury, subjective (self-reported) cognitive concerns and genetic risk for ADRD is also not well understood, particularly in diverse ancestry groups.MethodsUsing data from the U.S. Department of Veterans Affairs (VA) Million Veteran Program (MVP), we examined the relationship between dementia risk factors (APOE ε4, PTSD, TBI) and subjective cognitive concerns (SCC) measured in individuals of European (n = 140,921), African (n = 15,788), and Hispanic (n = 8,064) ancestry (EA, AA, and HA, respectively). We then used data from the VA electronic medical record to perform a retrospective survival analysis evaluating PTSD, TBI, APOE ε4, and SCC and their associations with risk of conversion to ADRD in Veterans aged 65 and older.ResultsPTSD symptoms (B = 0.50-0.52, p < 1E-250) and probable TBI (B = 0.05-0.19, p = 1.51E-07 - 0.002) were positively associated with SCC across all three ancestry groups. APOE ε4 was associated with greater SCC in EA Veterans aged 65 and older (B = 0.037, p = 1.88E-12). Results of Cox models indicated that PTSD symptoms (hazard ratio [HR] = 1.13-1.21), APOE ε4 (HR = 1.73-2.05) and SCC (HR = 1.18-1.37) were positively associated with risk for ADRD across all three ancestry groups. In the EA group, probable TBI also contributed to increased risk of ADRD (HR = 1.18).ConclusionsThe findings underscore the value of SCC as an indicator of ADRD risk in Veterans 65 and older when considered in conjunction with other influential genetic, clinical, and demographic risk factors.
| S-EPMC11218206 | biostudies-literature
Project description:Background and objectivePosttraumatic stress disorder (PTSD) is a serious and frequently debilitating psychiatric condition that can occur in people who have experienced traumatic stessors, such as war, violence, sexual assault and other life-threatening events. Treatment of PTSD and traumatic brain injury (TBI) in veterans is challenged by diagnostic complexity, partially due to PTSD and TBI symptom overlap and to the fact that subjective self-report assessments may be influenced by a patient's willingness to share their traumatic experiences and resulting symptoms. Corticotropin-releasing factor (CRF) is one of the main mediators of hypothalamic pituitary adrenal (HPA)-axis responses in stress and anxiety.Methods and resultsWe analyzed serum CRF levels in 230 participants including heathy controls (64), and individuals with PTSD (53), TBI (70) or PTSD+TBI (43) by enzyme immunoassay (EIA). Significantly lower CRF levels were found in both the PTSD and PTSD+TBI groups compared to healthy control (PTSD vs Controls: P=0.0014, PTSD + TBI vs Controls: P=0.0011) and chronic TBI participants (PTSD vs TBI: P<0.0001PTSD + TBI vs TBI: P<0.0001) , suggesting a PTSD-related mechanism independent from TBI and associated with CRF reduction. CRF levels negatively correlated with PTSD severity on the CAPS-5 scale in the whole study group.ConclusionsHyperactivation of the HPA axis has been classically identified in acute stress. However, the recognized enhanced feedback inhibition of the HPA axis in chronic stress supports our findings of lower CRF in PTSD patients. This study suggests that reduced serum CRF in PTSD should be further investigated. Future validation studies will establish if CRF is a possible blood biomarker for PTSD and/or for differentiating PTSD and chronic TBI symptomatology.
| S-EPMC8764614 | biostudies-literature
Project description:ObjectiveTo examine the association between the 5-HTTLPR polymorphism of the serotonin transporter (SLC6A4) gene, combat exposure, and posttraumatic stress disorder (PTSD) diagnosis and among two samples of combat-exposed veterans.MethodThe first sample included 550 non-Hispanic Black (NHB) combat-exposed veterans. The second sample included 555 non-Hispanic White (NHW) combat-exposed veterans. Participants were genotyped for the 5-HTTLPR/rs25531 variants of the SLC6A4 gene. A structured clinical interview was used to diagnose PTSD. Combat and civilian trauma exposure were assessed with validated self-report instruments. Logistic regression was used to test for main effects of 5-HTTLPR on PTSD diagnosis as well as gene x environment (GxE) interactions after adjusting for sex, ancestry proportion scores, civilian trauma exposure, and combat exposure.ResultsWithin the NHB sample, a significant additive effect was observed for 5-HTTLPR (OR = 1.502, p = .0025), such that the odds of having a current diagnosis of PTSD increased by 1.502 for each additional S' allele. No evidence for an association between 5-HTTLPR and PTSD was observed in the NHW sample. In addition, no evidence for combat x 5-HTTLPR effects were observed in either sample.ConclusionThe present study suggests that there may be an association between 5-HTTLPR genotype and PTSD diagnosis among NHB veterans; however, no evidence for the hypothesized 5-HTTLPR x combat interaction was found.
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Project description:Anxiety is characterized by excessive attention to threatening information, leading to impaired working memory (WM) performance and elevated anxious thoughts. Preliminary research indicates that individuals with PTSD show particular difficulty with WM in emotional contexts (Schweizer et al., 2011). Although several studies show that computerized training can improve WM capacity for anxious individuals (Owens et al., 2013; Schweizer et al., 2011; 2013), there has been very little research on WM training for PTSD or with Veterans (Saunders et al., 2015). In a pilot randomized trial, we assigned Veterans with elevated PTSD symptoms to an online emotional WM training, either adaptive (n-back; n = 11) or a less potent training (1-back; n = 10). Overall, both groups showed significant decreases in PTSD symptoms. The n-back group showed a trend of outperforming the 1-back group in improving reexperiencing symptoms (which are likely to be associated with impaired WM functioning). This population anecdotally found the intervention quite challenging, which may be why even the less potent 1-back was still helpful. These preliminary findings justify the effort for developing new WM-focused PTSD intervention for complex, vulnerable populations, particularly as online training can improve accessibility.
| S-EPMC6508098 | biostudies-literature
Project description:The present study examined fluctuation over time in symptoms of posttraumatic stress disorder (PTSD) among 34 combat veterans (28 with diagnosed PTSD, 6 with subclinical symptoms) assessed every 2 weeks for up to 2 years (range of assessments = 13-52). Temporal relationships were examined among four PTSD symptom clusters (reexperiencing, avoidance, emotional numbing, and hyperarousal) with particular attention to the influence of hyperarousal. Multilevel cross-lagged random coefficients autoregression for intensive time series data analyses were used to model symptom fluctuation decades after combat experiences. As anticipated, hyperarousal predicted subsequent fluctuations in the 3 other PTSD symptom clusters (reexperiencing, avoidance, emotional numbing) at subsequent 2-week intervals (rs = .45, .36, and .40, respectively). Additionally, emotional numbing influenced later reexperiencing and avoidance, and reexperiencing influenced later hyperarousal (rs = .44, .40, and .34, respectively). These findings underscore the important influence of hyperarousal. Furthermore, results indicate a bidirectional relationship between hyperarousal and reexperiencing as well as a possible chaining of symptoms (hyperarousal ? emotional numbing ? reexperiencing ? hyperarousal) and establish potential internal, intrapersonal mechanisms for the maintenance of persistent PTSD symptoms. Results suggested that clinical interventions targeting hyperarousal and emotional numbing symptoms may hold promise for PTSD of long duration.
| S-EPMC6785199 | biostudies-literature
Project description:Introduction: Psychiatric service dogs are increasingly being sought out by military veterans as a complementary intervention for posttraumatic stress disorder (PTSD). After receiving a service dog, many veterans continue training their service dog at home. Our objective was to explore the associations between training methods, PTSD severity, service dog behavior, and the veteran-service dog bond in a population of military veterans with PTSD. Methods: Post-9/11 military veterans with PTSD who had received a psychiatric service dog were recruited from a national service dog provider. A total of 111 veterans (M = 40.1 ± 8.3 years, 80% male) participated in an online survey regarding frequency of training methods, PTSD symptom severity, service dog behavior, and the human-animal bond. Service dogs were predominately Labrador Retriever purebreds or mixes of various breeds (66% male) and mostly obtained from shelters or rescues (58%). Training methods were divided into five categories: positive reinforcement (e.g., physical praise), negative punishment (e.g., ignoring the dog), positive punishment (e.g., verbal correction), dominance (e.g., alpha roll), and bond-based (e.g., co-sleeping). Data were analyzed using general linear models. Results: Veterans self-reported using all five categories of training methods at least once a month. More frequent use of positive punishment was associated with less closeness with their service dog (p = 0.02), more fear (p = 0.003), less eye contact (p < 0.0001), and less trainability (p = 0.04). More frequent use of positive reinforcement was associated with higher closeness to their service dog (p = 0.002) and perceived increased attachment behavior (p = 0.002) and playfulness (p = 0.002). More frequent use of bond-based methods was associated with higher closeness to their service dog (p = 0.02). PTSD severity was not significantly associated with reported dog behavior, temperament, or veteran-service dog closeness. Conclusion: Military veterans with PTSD service dogs reported using many training methods that were associated with different outcomes. In general, the reported use of positive reinforcement or bond-based training methods were associated with reporting more positive outcomes while the reported use of positive punishment was associated with reporting more negative outcomes. Educating service dog organizations and recipients about the impacts of training methods could be beneficial for service dog efficacy and welfare.
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