A Genome-Wide Association Study and Polygenic Risk Score Analysis of Posttraumatic Stress Disorder and Metabolic Syndrome in a South African Population.
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ABSTRACT:
SUBMITTER: Swart PC
PROVIDER: S-EPMC8222611 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The volume of subcortical structures represents a reliable, quantitative, and objective phenotype that captures genetic effects, environmental effects such as trauma, and disease effects such as posttraumatic stress disorder (PTSD). Trauma and PTSD represent potent exposures that may interact with genetic markers to influence brain structure and function. Genetic variants, associated with subcortical volumes in two large normative discovery samples, were used to compute polygenic scores (PGS) for the volume of seven subcortical structures. These were applied to a target sample enriched for childhood trauma and PTSD. Subcortical volume PGS from the discovery sample were strongly associated in our trauma/PTSD enriched sample (n = 7580) with respective subcortical volumes of the hippocampus (p = 1.10 × 10-20), thalamus (p = 7.46 × 10-10), caudate (p = 1.97 × 10-18), putamen (p = 1.7 × 10-12), and nucleus accumbens (p = 1.99 × 10-7). We found a significant association between the hippocampal volume PGS and hippocampal volume in control subjects from our sample, but was absent in individuals with PTSD (GxE; (beta = -0.10, p = 0.027)). This significant GxE (PGS × PTSD) relationship persisted (p < 1 × 10-19) in four out of five threshold peaks (0.024, 0.133, 0.487, 0.730, and 0.889) used to calculate hippocampal volume PGSs. We detected similar GxE (G × ChildTrauma) relationships in the amygdala for exposure to childhood trauma (rs4702973; p = 2.16 × 10-7) or PTSD (rs10861272; p = 1.78 × 10-6) in the CHST11 gene. The hippocampus and amygdala are pivotal brain structures in mediating PTSD symptomatology. Trauma exposure and PTSD modulate the effect of polygenic markers on hippocampal volume (GxE) and the amygdala volume PGS is associated with PTSD risk, which supports the role of amygdala volume as a risk factor for PTSD.
| S-EPMC8677780 | biostudies-literature
Project description:BACKGROUND:Metabolic syndrome (MetS), defined by a constellation of cardiometabolic pathologies, is highly prevalent among veterans, especially veterans with posttraumatic stress disorder (PTSD), and poses a major risk for adverse health outcomes, including neurodegeneration and mortality. Given this, we evaluated 1) the association between MetS and neural integrity, indexed by cortical thickness; 2) the relationship between PTSD and MetS; and 3) whether PTSD was associated with cortical thickness indirectly through MetS. METHODS:The sample consisted of 346 U.S. military veterans (89.3% male; 71.4% white) who deployed to Iraq, Afghanistan, or both. Neuroimaging data were available for 274 participants. RESULTS:In whole-brain analyses, MetS was negatively associated with cortical thickness in two left and four right hemisphere regions, as follows: bilateral temporal lobe, including temporal pole, fusiform gyrus, and insula, and extending into occipital cortex (left hemisphere) and orbitofrontal cortex (right hemisphere); bilateral precuneus, posterior cingulate, calcarine, and occipital-parietal cortex; and right rostral anterior cingulate cortex and central sulcus/postcentral gyrus. Path models showed that PTSD predicted MetS (? = .19, p < .001), which was associated with reduced cortical thickness (? = -.29 to -.43, all p < .001). CONCLUSIONS:Results from this young veteran sample provide evidence that PTSD confers risk for cardiometabolic pathology and neurodegeneration and raise concern that this cohort may be aging prematurely and at risk for substantial medical and cognitive decline. This study highlights the need to identify the molecular mechanisms linking PTSD to MetS and effective interventions to reduce PTSD-related health comorbidities.
| S-EPMC4899313 | biostudies-literature
Project description:BackgroundGenome-wide polygenic scores (GPS) integrate information from many common DNA variants into a single number. Because rates of coronary artery disease (CAD) are substantially higher among South Asians, a GPS to identify high-risk individuals may be particularly useful in this population.ObjectivesThis analysis used summary statistics from a prior genome-wide association study to derive a new GPSCAD for South Asians.MethodsThis GPSCAD was validated in 7,244 South Asian UK Biobank participants and tested in 491 individuals from a case-control study in Bangladesh. Next, a static ancestry and GPSCAD reference distribution was built using whole-genome sequencing from 1,522 Indian individuals, and a framework was tested for projecting individuals onto this static ancestry and GPSCAD reference distribution using 1,800 CAD cases and 1,163 control subjects newly recruited in India.ResultsThe GPSCAD, containing 6,630,150 common DNA variants, had an odds ratio (OR) per SD of 1.58 in South Asian UK Biobank participants and 1.60 in the Bangladeshi study (p < 0.001 for each). Next, individuals of the Indian case-control study were projected onto static reference distributions, observing an OR/SD of 1.66 (p < 0.001). Compared with the middle quintile, risk for CAD was most pronounced for those in the top 5% of the GPSCAD distribution-ORs of 4.16, 2.46, and 3.22 in the South Asian UK Biobank, Bangladeshi, and Indian studies, respectively (p < 0.05 for each).ConclusionsThe new GPSCAD has been developed and tested using 3 distinct South Asian studies, and provides a generalizable framework for ancestry-specific GPS assessment.
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Project description:Patients with posttraumatic stress disorder (PTSD) exhibit an increased state of inflammation. Various animal models for PTSD have shown some of the same immune imbalances as have been shown in human subjects with PTSD, and some of these studies are discussed in this review. However, animal studies can only indirectly implicate immune involvement in PTSD in humans. This review of mainly studies with human subjects focuses on dissecting the immunological role in the pathogenesis of PTSD following initial trauma exposure. It addresses both the inflammatory state associated with PTSD and the immune imbalance between stimulatory and inhibitory immune mediators, as well as variables that can lead to discrepancies between analyses. The concept of immunological treatment approaches is proposed for PTSD, as new treatments are needed for this devastating disorder that is affecting unprecedented numbers of Veterans from the long-standing wars in the Middle East and which affects civilians following severe trauma.
| S-EPMC5681483 | biostudies-literature
Project description:BACKGROUND:Genetic polymorphisms that influence serotonin (5-hydroxytryptamine, 5HT) neurotransmission are candidates for contributing to susceptibility to posttraumatic stress disorder (PTSD). The objective of our study was to determine if a variable length polymorphism for the promoter regions of the 5HT transporter (5HTTLPR), and/or a substitution polymorphism in the promoter region for the 5HT2A receptor, would be associated with PTSD in a trauma exposed population of adult African-Americans. METHODS:Using a case control design, 118 participants recruited from the primary care clinics and the campus of a historically black university who met inclusion criteria including trauma exposure provided blood samples for genomic DNA. PTSD criteria were determined by the Clinician Assessment of PTSD Scale (CAPS) and criteria for other psychiatric disorders by the Structured Clinical Interview for DSM-IV (SCID). 5HTTLPR and 5HT2A-1438A/G were genotyped using established methods. Associations of genotypes with lifetime PTSD, and models testing associations of allele "dose", were analyzed. RESULTS:Fifty-five (47%) participants met lifetime criteria for PTSD and 26 (22%) met criteria for (mostly comorbid) major depression. The 5HT2A (lower expressing) G allele was significantly associated with PTSD. We did not find significant associations with 5HTTLPR. CONCLUSIONS:Our findings suggest a relationship between genetic variation in the 5HT2A promoter region and PTSD.
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Project description:BACKGROUND:The 2015 outbreak of Middle East Respiratory Syndrome (MERS) in the Republic of Korea is a recent and representative occurrence of nationwide outbreaks of Emerging Infectious Diseases (EIDs). In addition to physical symptoms, posttraumatic stress disorder (PTSD) and depression are common following outbreaks of EID. METHODS:The present study investigated the long-term mental health outcomes and related risk factors in survivors of MERS. A prospective nationwide cohort study was conducted 12 months after the MERS outbreak at multi-centers throughout Korea. PTSD and depression as the main mental health outcomes were assessed with the Impact of Event Scale-Revised Korean version (IES-R-K) and the Patient Health Questionnaire-9 (PHQ-9) respectively. RESULTS:42.9% of survivors reported PTSD (IES-R-K ≥ 25) and 27.0% reported depression (PHQ-9 ≥ 10) at 12 months post-MERS. A multivariate analysis revealed that anxiety (adjusted odds ratio [aOR], 5.76; 95%CI, 1.29-25.58; P = 0.021), and a greater recognition of stigma (aOR, 11.09, 95%CI, 2.28-53.90; P = 0.003) during the MERS-affected period were independent predictors of PTSD at 12 months after the MERS outbreak. Having a family member who died from MERS predicted the development of depression (aOR, 12.08, 95%CI, 1.47-99.19; P = 0.020). CONCLUSION:This finding implies that psychosocial factors, particularly during the outbreak phase, influenced the mental health of patients over a long-term period. Mental health support among the infected subjects and efforts to reduce stigma may improve recovery from psychological distress in an EID outbreak.
| S-EPMC7224724 | biostudies-literature
Project description:Genetic factors influence the risk for posttraumatic stress disorder (PTSD), a potentially chronic and disabling psychiatric disorder that can arise after exposure to trauma. Candidate gene association studies have identified few genetic variants that contribute to PTSD risk.We conducted genome-wide association analyses in 1578 European Americans (EAs), including 300 PTSD cases, and 2766 African Americans, including 444 PTSD cases, to find novel common risk alleles for PTSD. We used the Illumina Omni1-Quad microarray, which yielded approximately 870,000 single nucleotide polymorphisms (SNPs) suitable for analysis.In EAs, we observed that one SNP on chromosome 7p12, rs406001, exceeded genome-wide significance (p = 3.97 × 10(-8)). A SNP that maps to the first intron of the Tolloid-Like 1 gene (TLL1) showed the second strongest evidence of association, although no SNPs at this locus reached genome-wide significance. We then tested six SNPs in an independent sample of nearly 2000 EAs and successfully replicated the association findings for two SNPs in the first intron of TLL1, rs6812849 and rs7691872, with p values of 6.3 × 10(-6) and 2.3 × 10(-4), respectively. In the combined sample, rs6812849 had a p value of 3.1×10(-9). No significant signals were observed in the African American part of the sample. Genome-wide association study analyses restricted to trauma-exposed individuals yielded very similar results.This study identified TLL1 as a new susceptibility gene for PTSD.
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Project description:PURPOSE:Depression and posttraumatic stress disorder (PTSD) may be linked to the metabolic syndrome (MetS). Consistency of this association across ethnic groups and the influence of comorbidity of depression/PTSD were examined. METHODS:Cross-sectional baseline data from the HELIUS study were used (4527 Dutch, 2999 South-Asian Surinamese, 4058 African Surinamese, 2251 Ghanaian, 3522 Turkish and 3825 Moroccan participants). The Patient Health Questionnaire-9 (PHQ-9) (score range 0-27) measured depressive symptoms. A 9-item questionnaire (score range 0-9) measured PTSD symptoms. The MetS was defined according to the International Diabetes Federation. The association of a depressed mood (PHQ-9 sum score???10) and severe PTSD symptoms (sum score???7) with the MetS was examined using logistic regression. Interaction with ethnicity and between a depressed mood and severe PTSD symptoms was tested. RESULTS:A depressed mood was associated with the MetS [OR (95% CI)?=?1.37 (1.24-1.51)] in the total sample and consistent across ethnic groups (p values for interaction all >?0.05). Severe PTSD symptoms were significantly associated with the MetS in the Dutch [OR (95% CI)?=?1.71 (1.07-2.73)]. The South-Asian Surinamese, Turks and Moroccans showed weaker associations than the Dutch (p values for interaction all <?0.05). A depressed mood and severe PTSD symptoms did not interact in the association with the MetS (p values for interaction?>?0.05). CONCLUSIONS:A depressed mood was consistently associated with the MetS across ethnic groups, but the association between severe PTSD symptoms and the MetS maybe ethnicity dependent. The association with the MetS was not different in case of depressed mood/severe PTSD symptoms comorbidity.
| S-EPMC6133160 | biostudies-literature
Project description:People involved with criminal justice frequently are exposed to violence and traumatic experiences. This may lead to posttraumatic stress disorder (PTSD); however, no review, to our knowledge, has synthetized findings in this setting. We conducted a systematic review and meta-analysis to estimate prevalence rates of PTSD in prison populations. Original studies in which prevalence rates of PTSD in unselected samples of incarcerated people were reported were systematically searched between 1980 and June 2017. Data were pooled using random-effects meta-analysis, and sources of heterogeneity for prespecified characteristics were assessed by meta-regression. We identified 56 samples comprising 21,099 imprisoned men and women from 20 countries. Point prevalence of PTSD ranged from 0.1% to 27% for male, and from 12% to 38% for female prisoner populations. The random-effects pooled point prevalence was 6.2% (95% confidence interval: 3.9, 9.0) in male prisoners and 21.1% (95% confidence interval: 16.9, 25.6) in female prisoners. The heterogeneity between the included studies was very high. Higher prevalence was reported in samples of female prisoners, smaller studies (n < 100), and for investigations based in high-income countries. Existing evidence shows high levels of PTSD among imprisoned people, especially women. Psychosocial interventions to prevent violence, especially against children and women, and to mitigate its consequences in marginalized communities must be improved. Trauma-informed approaches for correctional programs and scalable PTSD treatments in prisons require further consideration.
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Project description:BACKGROUND: Many patients with Posttraumatic Stress Disorder (PTSD) feel overwhelmed in situations with high levels of sensory input, as in crowded situations with complex sensory characteristics. These difficulties might be related to subtle sensory processing deficits similar to those that have been found for sounds in electrophysiological studies. METHOD: Visual processing was investigated with functional magnetic resonance imaging in trauma-exposed participants with (N = 18) and without PTSD (N = 21) employing a picture-viewing task. RESULTS: Activity observed in response to visual scenes was lower in PTSD participants 1) in the ventral stream of the visual system, including striate and extrastriate, inferior temporal, and entorhinal cortices, and 2) in dorsal and ventral attention systems (P < 0.05, FWE-corrected). These effects could not be explained by the emotional salience of the pictures. CONCLUSIONS: Visual processing was substantially altered in PTSD in the ventral visual stream, a component of the visual system thought to be responsible for object property processing. Together with previous reports of subtle auditory deficits in PTSD, these findings provide strong support for potentially important sensory processing deficits, whose origins may be related to dysfunctional attention processes.
| S-EPMC3871398 | biostudies-other