Genome-Wide Genetic Analysis of Dropout in a Controlled Exercise Intervention in Sedentary Adults With Overweight or Obesity and Cardiometabolic Disease.

BACKGROUND: Despite the benefits of exercise, many individuals are unable or unwilling to adopt an exercise intervention. PURPOSE: The purpose of this analysis was to identify putative genetic variants associated with dropout from exercise training interventions among individuals in the STRRIDE trials. METHODS: We used a genome-wide association study approach to identify genetic variants in 603 participants initiating a supervised exercise intervention. Exercise intervention dropout occurred when a subject withdrew from further participation in the study or was otherwise lost to follow-up. RESULTS: Exercise intervention dropout was associated with a cluster of single-nucleotide polymorphisms with the top candidate being rs722069 (T/C, risk allele = C) (unadjusted p = 2.2 × 10-7, odds ratio = 2.23) contained within a linkage disequilibrium block on chromosome 16. In Genotype-Tissue Expression, rs722069 is an expression quantitative trait locus of the EARS2, COG7, and DCTN5 genes in skeletal muscle tissue. In subsets of the STRRIDE genetic cohort with available muscle gene expression (n = 37) and metabolic data (n = 82), at baseline the C allele was associated with lesser muscle expression of EARS2 (p < .002) and COG7 (p = .074) as well as lesser muscle concentrations of C2- and C3-acylcarnitines (p = .026). CONCLUSIONS: Our observations imply that exercise intervention dropout is genetically moderated through alterations in gene expression and metabolic pathways in skeletal muscle. Individual genetic traits may allow the development of a biomarker-based approach for identifying individuals who may benefit from more intensive counseling and other interventions to optimize exercise intervention adoption. CLINICAL TRIAL INFORMATION: STRRIDE I = NCT00200993; STRRIDE AT/RT = NCT00275145; STRRIDE-PD = NCT00962962.

Regular participation in exercise can provide a myriad of health benefits. Although individuals recognize these benefits, many are unable or unwilling to adopt an exercise intervention once initiated. The purpose of this analysis was to identify genetic variants associated with dropout from an exercise training intervention. We found exercise intervention dropout to be genetically moderated through changes in gene expression and metabolic pathways in muscle. Thus, individual genetic traits may allow for the development of a biomarker-based targeted approach for identifying individuals who may benefit from more intensive counseling and interventions to optimize the adoption of an exercise intervention program.

Sex and race differences of cerebrospinal fluid metabolites in healthy individuals.

INTRODUCTION: Analyses of cerebrospinal fluid (CSF) metabolites in large, healthy samples have been limited and potential demographic moderators of brain metabolism are largely unknown. OBJECTIVE: Our objective in this study was to examine sex and race differences in 33 CSF metabolites within a sample of 129 healthy individuals (37 African American women, 29 white women, 38 African American men, and 25 white men). METHODS: CSF metabolites were measured with a targeted electrochemistry-based metabolomics platform. Sex and race differences were quantified with both univariate and multivariate analyses. Type I error was controlled for by using a Bonferroni adjustment (0.05/33 = .0015). RESULTS: Multivariate Canonical Variate Analysis (CVA) of the 33 metabolites showed correct classification of sex at an average rate of 80.6% and correct classification of race at an average rate of 88.4%. Univariate analyses revealed that men had significantly higher concentrations of cysteine (p < 0.0001), uric acid (p < 0.0001), and N-acetylserotonin (p = 0.049), while women had significantly higher concentrations of 5-hydroxyindoleacetic acid (5-HIAA) (p = 0.001). African American participants had significantly higher concentrations of 3-hydroxykynurenine (p = 0.018), while white participants had significantly higher concentrations of kynurenine (p < 0.0001), indoleacetic acid (p < 0.0001), xanthine (p = 0.001), alpha-tocopherol (p = 0.007), cysteine (p = 0.029), melatonin (p = 0.036), and 7-methylxanthine (p = 0.037). After the Bonferroni adjustment, the effects for cysteine, uric acid, and 5-HIAA were still significant from the analysis of sex differences and kynurenine and indoleacetic acid were still significant from the analysis of race differences. CONCLUSION: Several of the metabolites assayed in this study have been associated with mental health disorders and neurological diseases. Our data provide some novel information regarding normal variations by sex and race in CSF metabolite levels within the tryptophan, tyrosine and purine pathways, which may help to enhance our understanding of mechanisms underlying sex and race differences and potentially prove useful in the future treatment of disease.

Correction to: Low Life Course Socioeconomic Status (SES) Is Associated with Negative NEO PI-R Personality Patterns.

After the publication of the original article, the Editor was notified by Duke University that they have determined the authorship to be incomplete. Consequently, Dr Edward Suarez has been added as a co-author to represent his contribution to the conception and design of the work and acquisition of the data.

Associations of self-reported eating disorder behaviors and personality in a college-educated sample.

OBJECTIVE: In order to better understand factors motivating eating disorder (ED) behaviors and better identify persons at-risk for these behaviors, we sought to identify which personality domains and facets were associated with behaviors for weight control. METHODS: ED behavior information was gathered from the University of North Carolina Alumni Heart Study using the question, "have you ever used any of the following to lose weight?" Respondents endorsed any combination of the following: "Vomiting," "Fasting," "Laxatives," "Excessive physical exercise." Personality was measured using the Revised NEO Personality Inventory (NEO-PI-R). One-way ANOVAs were performed comparing personality domains and facets to reported ED behaviors, computed both as separate behaviors and the number of cumulative behaviors. RESULTS: Of 3496 respondents, 9.41% endorsed ever having used at least one ED behavior, with the majority endorsing only a single ED behavior. For both sexes, endorsing greater numbers of ED behaviors was associated with higher scores on Neuroticism and Openness. For women, the strongest associations for behaviors with personality were: excessive exercise with high Impulsiveness; fasting with high Impulsiveness and low Gregariousness; laxative use/purging with high scores on Activity and Feelings. For men, the strongest associations were: excessive exercise with high Impulsiveness; fasting with high Ideas; laxative use/purging with low Modesty. DISCUSSION: Data collected from this sample showed a sex-modulated pattern of association between personality domains and facets with ED behaviors. Our findings support that obtaining personality profiles of individuals exhibiting subclinical eating behaviors will enhance our understanding of who is at risk of developing an ED diagnosis.

The role of genetic and environmental influences on the association between childhood ADHD symptoms and BMI.

BACKGROUND/OBJECTIVES: Although childhood attention deficit hyperactivity disorder (ADHD) has been previously associated with concurrent and later obesity in adulthood, the etiology of this association remains unclear. The objective of this study is to determine the shared genetic effects of ADHD symptoms and BMI in a large sample of sibling pairs, consider how these shared effects may vary over time, and examine potential sex differences. SUBJECT/METHODS: Sibling pair data were obtained from the National Longitudinal Study of Adolescent to Adult Health (Add Health); childhood ADHD symptoms were reported retrospectively during young adulthood, while three prospective measurements of BMI were available from young adulthood to later adulthood. Cholesky decomposition models were fit to this data using Mx and maximum-likelihood estimation. The twin and sibling sample for these analyses included: 221 monozygotic (MZ) pairs (92 male-male, 139 female-female), 228 dizygotic (DZ) pairs (123 male-male, 105 female-female), 471 full-sibling (FS) pairs (289 male-male, 182 female-female), 106 male-female DZ twin pairs, and 234 male-female FS pairs. RESULTS: The magnitude of the association between childhood ADHD symptoms and BMI changed over time and by sex. The etiological relationship between childhood ADHD symptoms and the three prospective measurements of BMI differed for males and females, such that unique or non-shared environmental influences contributed to the relationship within males and genetic factors contributed to the relationship within females. Specifically, among females, genetic influences on childhood ADHD symptoms were partially shared with those effecting BMI and increased from adolescence to later adulthood (genetic correlation = 0.20 (95% CI: 0.07-0.36) in adolescence and 0.24 (95% CI: 0.10, 0.41) in adulthood). CONCLUSION: Genetic influences on ADHD symptoms in childhood are partially shared with those effecting obesity. However, future research is needed to determine why this association is limited to females.

The Effects of Tryptophan Enhancement and Depletion on Plasma Catecholamine Levels in Healthy Individuals.

OBJECTIVE: Central nervous system (CNS) serotonin (5-HT) exerts both excitatory and inhibitory effects on the sympathetic nervous system (SNS) in animals. In this study, we examine the effects of tryptophan enhancement and depletion on plasma catecholamine levels in humans. METHODS: The total sample consisted of 164 healthy men and women who were tested for 2 days. Seventy-nine participants were randomized to a tryptophan enhancement condition and 85 to a tryptophan depletion condition. Both protocols consisted of a "sham day," followed by an "active day." Blood samples for assessment of plasma norepinephrine and epinephrine levels were collected before and after tryptophan enhancement/depletion. Data were analyzed using general linear models. Separate analyses were conducted for each study arm and for each measure. RESULTS: In the depletion condition, both epinephrine (F(5,330) = 2.69, p = .021) and norepinephrine (F(5,335) = 2.79, p = .018) showed small increases on active versus "sham" depletion days. There were also significant day by time interactions for epinephrine (F(3,171) = 39.32, p < .0001) and norepinephrine (F(3,195) = 31.09, p < .0001) levels in the enhancement arm. Tryptophan infusion resulted in a marked increase in epinephrine (Premean = 23.92 (12.23) versus Postmean = 81.57 (62.36)) and decrease in norepinephrine (Premean = 257.2 (106.11) versus Postmean = 177.04 (87.15)), whereas levels of both catecholamines were stable on the "sham day." CONCLUSIONS: CNS 5-HT exerts both inhibitory and excitatory effects on SNS activity in humans, potentially due to stimulation of CNS 5-HT receptors that have shown to have inhibitory (5-HT1A) and excitatory (5-HT1A and/or 5-HT2) SNS effects in animal models.

Brain-derived neurotrophic factor rs6265 (Val66Met) polymorphism is associated with disease severity and incidence of cardiovascular events in a patient cohort.

BACKGROUND: The rs6265 (Val66Met) single-nucleotide polymorphism in the BDNF gene has been related to a number of endophenotypes that have in turn been shown to confer risk for atherosclerotic cardiovascular disease (CVD). To date, however, very few studies have examined the association of the Val66Met single-nucleotide polymorphism with CVD clinical outcomes. METHODS: In a cohort of 5,510 Caucasian patients enrolled in the CATHeterization GENetics (CATHGEN) study at Duke University Hospital between 2001 and 2011, we determined the severity of coronary artery disease (CAD) and CVD event incidence through up to 11.8years of follow-up. We examined the association of Val66Met genotype with time-to-death or myocardial infarction, adjusting for age, sex, CAD risk variables, and CAD severity measures. RESULTS: The Val/Val genotype was associated with a higher risk than Met carriers for clinical CVD events (P=.034, hazard ratio 1.12, 95% CI 1.01-1.24). In addition, compared with Met carriers, individuals with the Val/Val genotype had a greater odds of having more diseased vessels (odds ratio 1.17, 95% CI 1.06-1.30, P=.002), and lower left ventricular ejection fraction (ß=-0.72, 95% CI, -1.42 to -0.02, P=.044). CONCLUSIONS: The Val/Val genotype was associated with greater severity of CAD and incidence of CVD-related clinical events in a patient sample. If these findings are confirmed in further research, intervention studies in clinical groups with the Val/Val genotype could be undertaken to prevent disease and improve prognosis.

Population differences in associations of serotonin transporter promoter polymorphism (5HTTLPR) di- and triallelic genotypes with blood pressure and hypertension prevalence.

Based on prior research finding the 5HTTLPR L allele associated with increased cardiovascular reactivity to laboratory stressors and increased risk of myocardial infarction, we hypothesized that the 5HTTLPR L allele will be associated with increased blood pressure (BP) and increased hypertension prevalence in 2 large nationally representative samples in the United States and Singapore. METHODS: Logistic regression and linear models tested associations between triallelic (L'S', based on rs25531) 5HTTLPR genotypes and hypertension severity and mean systolic and diastolic blood pressure (SBP and DBP) collected during the Wave IV survey of the National Longitudinal Study of Adolescent to Adult Health (Add Health, N=11,815) in 2008-09 and during 2004-07 in 4196 Singaporeans. RESULTS: In US Whites, L' allele carriers had higher SBP (0.9 mm Hg, 95% CI=0.26-1.56) and greater odds (OR=1.23, 95% CI=1.10-1.38) of more severe hypertension than those with S'S' genotypes. In African Americans, L' carriers had lower mean SBP (-1.27mm Hg, 95% CI=-2.53 to -0.01) and lower odds (OR = 0.78, 95% CI=0.65-0.94) of more severe hypertension than those with the S'S' genotype. In African Americans, those with L'L' genotypes had lower DBP (-1.13mm Hg, 95% CI=-2.09 to -0.16) than S' carriers. In Native Americans, L' carriers had lower SBP (-6.05mm Hg, 95% CI=-9.59 to -2.51) and lower odds of hypertension (OR = 0.34, 95% CI=0.13-0.89) than those with the S'S' genotype. In Asian/Pacific Islanders those carrying the L' allele had lower DBP (-1.77mm Hg, 95% CI=-3.16 to -0.38) and lower odds of hypertension (OR = 0.68, 95% CI=0.48-0.96) than those with S'S'. In the Singapore sample S' carriers had higher SBP (3.02mm Hg, 95% CI=0.54-5.51) and DBP (1.90mm Hg, 95% CI=0.49-3.31) than those with the L'L' genotype. CONCLUSIONS: These findings suggest that Whites carrying the L' allele, African Americans and Native Americans with the S'S' genotype, and Asians carrying the S' allele will be found to be at higher risk of developing cardiovascular disease and may benefit from preventive measures.

Neuroticism Increases PTSD Symptom Severity by Amplifying the Emotionality, Rehearsal, and Centrality of Trauma Memories.

OBJECTIVE: Although it is well established that neuroticism increases the risk of posttraumatic stress disorder (PTSD), little is known about the mechanisms that promote PTSD in individuals with elevated levels of neuroticism. Across two studies, we examined the cognitive-affective processes through which neuroticism leads to greater PTSD symptom severity. METHOD: Community-dwelling adults with trauma histories varying widely in severity (Study 1) and clinically diagnosed individuals exposed to DSM-IV-TR A1 criterion traumas (Study 2) completed measures of neuroticism, negative affectivity, trauma memory characteristics, and PTSD symptom severity. RESULTS: Longitudinal data in Study 1 showed that individuals with higher scores on two measures of neuroticism assessed approximately three decades apart in young adulthood and midlife reported trauma memories accompanied by more intense physiological reactions, more frequent involuntary rehearsal, and greater perceived centrality to identity in older adulthood. These properties of trauma memories were in turn associated with more severe PTSD symptoms. Study 2 replicated these findings using cross-sectional data from individuals with severe trauma histories and three additional measures of neuroticism. CONCLUSIONS: Results suggest that neuroticism leads to PTSD symptoms by magnifying the emotionality, availability, and centrality of trauma memories as proposed in mnemonic models of PTSD.

Computing a Synthetic Chronic Psychosocial Stress Measurement in Multiple Datasets and its Application in the Replication of G × E Interactions of the EBF1 Gene.

Chronic psychosocial stress adversely affects health and is associated with the development of disease [Williams, 2008]. Systematic epidemiological and genetic studies are needed to uncover genetic variants that interact with stress to modify metabolic responses across the life cycle that are the proximal contributors to the development of cardiovascular disease and precipitation of acute clinical events. Among the central challenges in the field are to perform and replicate gene-by-environment (G × E) studies. The challenge of measurement of individual experience of psychosocial stress is magnified in this context. Although many research datasets exist that contain genotyping and disease-related data, measures of psychosocial stress are often either absent or vary substantially across studies. In this paper, we provide an algorithm to create a synthetic measure of chronic psychosocial stress across multiple datasets, applying a consistent criterion that uses proxy indicators of stress components. We validated the computed scores of chronic psychosocial stress by observing moderately strong and significant correlations with the self-rated chronic psychosocial stress in the Multi-Ethnic Study of Atherosclerosis Cohort (Rho = 0.23, P < 0.0001) and with the measures of depressive symptoms in five datasets (Rho = 0.15-0.42, Ps = 0.005 to <0.0001) and by comparing the distributions of the self-rated and computed measures. Finally, we demonstrate the utility of this computed chronic psychosocial stress variable by providing three additional replications of our previous finding of gene-by-stress interaction with central obesity traits [Singh et al., 2015].

Personality Traits and Successful Aging: Findings From the Georgia Centenarian Study.

The current study attempted to describe how personality traits of older adults are associated with components of successful aging (cognition, volunteering, activities of daily living, and subjective health). Three-hundred and six octogenarians and centenarians who participated in the third phase of the Georgia Centenarian Study provided data for this study. Factor analysis was conducted to test the existence of two higher-order factors of the Big Five personality traits, and a two-factor model (alpha and beta) fit the data well. Also, blocked multiple regression analysis was conducted to examine the association between personality traits and four components of successful aging. Results indicated that low scores on neuroticism and high scores on extraversion, openness to experience, agreeableness, and conscientiousness are significantly related to the components of successful aging. After controlling for demographic variables (age, gender, residential type, and race/ethnicity), alpha (i.e., emotional stability, agreeableness, and conscientiousness) was associated with higher levels of cognition, higher likelihood of engaging in volunteer work, higher levels of activities of daily living, and higher levels of subjective health. Beta (i.e., extraversion and openness to experience) was also positively associated with cognition and engaging in volunteer work.

Population frequencies of the Triallelic 5HTTLPR in six Ethnicially diverse samples from North America, Southeast Asia, and Africa.

Genetic differences between populations are potentially an important contributor to health disparities around the globe. As differences in gene frequencies influence study design, it is important to have a thorough understanding of the natural variation of the genetic variant(s) of interest. Along these lines, we characterized the variation of the 5HTTLPR and rs25531 polymorphisms in six samples from North America, Southeast Asia, and Africa (Cameroon) that differ in their racial and ethnic composition. Allele and genotype frequencies were determined for 24,066 participants. Results indicated higher frequencies of the rs25531 G-allele among Black and African populations as compared with White, Hispanic and Asian populations. Further, we observed a greater number of 'extra-long' ('XL') 5HTTLPR alleles than have previously been reported. Extra-long alleles occurred almost entirely among Asian, Black and Non-White Hispanic populations as compared with White and Native American populations where they were completely absent. Lastly, when considered jointly, we observed between sample differences in the genotype frequencies within racial and ethnic populations. Taken together, these data underscore the importance of characterizing the L-G allele to avoid misclassification of participants by genotype and for further studies of the impact XL alleles may have on the transcriptional efficiency of SLC6A4.

Associations between central nervous system serotonin, fasting glucose, and hostility in African American females.

BACKGROUND: Previous research has shown an association between hostility and fasting glucose in African American women. Central nervous system serotonin activity is implicated both in metabolic processes and in hostility related traits. PURPOSE: The purpose of this study is to determine whether central nervous system serotonin influences the association between hostility and fasting glucose in African American women. METHODS: The study consisted of 119 healthy volunteers (36 African American women, 27 White women, 21 White males, and 35 African American males, mean age 34 ± 8.5 years). Serotonin related compounds were measured in cerebrospinal fluid. Hostility was measured by the Cook-Medley Hostility Scale. RESULTS: Hostility was associated with fasting glucose and central nervous system serotonin related compounds in African American women only. Controlling for the serotonin related compounds significantly reduced the association of hostility to glucose. CONCLUSIONS: The positive correlation between hostility and fasting glucose in African American women can partly be explained by central nervous system serotonin function.

Personality Structure Among Centenarians: The Georgia Centenarian Study.

UNLABELLED: BACKGROUND/STUDY CONTEXT: We demonstrate that observer-rated factor structure of personality in centenarians is congruent with the normative structure. Prevalence of cognitive impairment, which has previously been linked to changes in personality in younger samples, is high in this age group, requiring observer ratings to obtain valid data in a population-based context. Likewise, the broad range of cognitive functioning necessitates synthesis of results across multiple measures of cognitive performance. METHODS AND RESULTS: Data from 161 participants in the Georgia Centenarian Study (GCS; MAge = 100.3 years, 84% women, 20% African American, 40% community-dwelling, 30% low cognitive functioning) support strong overall correspondence with reference structure (full sample: .94; higher cognitive functioning: .94; lower cognitive functioning: .90). Centenarians with lower cognitive functioning are higher on neuroticism and lower on openness to experience, agreeableness, and conscientiousness. Facet-level differences (higher N1-N6: anxiety, hostility, depression, self-consciousness, impulsiveness, vulnerability to stress; lower E1: warmth; lower O4-O6: actions, ideas, values; lower A1, A3, A4: trust, altruism, compliance; C1, C5: competence, self-discipline) are also observed. Multivariate factor-level models indicate only neuroticism of the five broad factors predicts membership in cognitively impaired group; facet-level models showed that lower-order scales from three of the five domains were significant. Centenarians with higher self-consciousness (N4), impulsiveness (N5), and deliberation (C6) but lower ideas (O5), compliance (A4), and self-discipline (C5) were more likely to be in the lower cognitive functioning category. CONCLUSION: Results present first normative population-based data for personality structure in centenarians and offer intriguing possibilities for the role of personality in cognitive impairment centered on neuroticism.

Personality facets and all-cause mortality among Medicare patients aged 66 to 102 years: a follow-on study of Weiss and Costa (2005).

OBJECTIVE: To investigate associations between personality facets and survival during an 8-year follow-up. METHODS: In 597 Medicare recipients (age, 66-102 years) followed up for approximately 8 years, personality domains and facets were assessed using the Revised NEO Personality Inventory (NEO-PI-R). This study builds on a previous study which used proportional hazards regression to test whether the NEO-PI-R factor and selected facet scores were associated with mortality risk. That study revealed that the neuroticism facet impulsiveness, agreeableness facet straightforwardness, and conscientiousness facet self-discipline were related to lower risk during 4 years of follow-up. We extended the follow-up period by 4 years, examined all 30 facets, and used accelerated failure time modeling as an additional analytic approach. Unlike proportional hazards regression, accelerated failure time modeling permits inferences about the median survival length conferred by predictors. Each facet was tested in a model that included health-related covariates and NEO-PI-R factor scores for dimensions that did not include that facet. RESULTS: Over the 8-year follow-up period, impulsiveness was not significant, each standard deviation of straightforwardness was associated with an 11% increase in median survival time and, when dichotomized, higher self-discipline was associated with a 34% increase in median survival time. Each standard deviation of altruism, compliance, tender-mindedness, and openness to fantasy was associated with a 9% to 11% increase in median survival time. CONCLUSIONS: After extending the follow-up period from 4 to 8 years, self-discipline remained a powerful predictor of survival and facets associated with imagination, generosity, and higher-quality interpersonal interactions become increasingly important.

Changes in neuroticism following trauma exposure.

Using longitudinal data, the present study examined change in midlife neuroticism following trauma exposure. Our primary analyses included 670 participants (M(age) = 60.55; 65.22% male, 99.70% Caucasian) who completed the NEO Personality Inventory at ages 42 and 50 and reported their lifetime exposure to traumatic events approximately 10 years later. No differences in pre- and post-trauma neuroticism scores were found among individuals who experienced all of their lifetime traumas in the interval between the personality assessments. Results were instead consistent with normative age-related declines in neuroticism throughout adulthood. Furthermore, longitudinal changes in neuroticism scores did not differ between individuals with and without histories of midlife trauma exposure. Examination of change in neuroticism following life-threatening traumas yielded a comparable pattern of results. Analysis of facet-level scores largely replicated findings from the domain scores. Overall, our findings suggest that neuroticism does not reliably change following exposure to traumatic events in middle adulthood. Supplemental analyses indicated that individuals exposed to life-threatening traumas in childhood or adolescence reported higher midlife neuroticism than individuals who experienced severe traumas in adulthood. Life-threatening traumatic events encountered early in life may have a more pronounced impact on adulthood personality than recent traumatic events.

Cumulative exposure to traumatic events in older adults.

OBJECTIVES: The present study examined the impact of cumulative trauma exposure on current posttraumatic stress disorder (PTSD) symptom severity in a nonclinical sample of adults in their 60s. The predictive utility of cumulative trauma exposure was compared to other known predictors of PTSD, including trauma severity, personality traits, social support, and event centrality. METHOD: Community-dwelling adults (n = 2515) from the crest of the Baby Boom generation completed the Traumatic Life Events Questionnaire, the PTSD Checklist, the NEO Personality Inventory, the Centrality of Event Scale, and rated their current social support. RESULTS: Cumulative trauma exposure predicted greater PTSD symptom severity in hierarchical regression analyses consistent with a dose-response model. Neuroticism and event centrality also emerged as robust predictors of PTSD symptom severity. In contrast, the severity of individuals' single most distressing life event, as measured by self-report ratings of the A1 PTSD diagnostic criterion, did not add explanatory variance to the model. Analyses concerning event categories revealed that cumulative exposure to childhood violence and adulthood physical assaults were most strongly associated with PTSD symptom severity in older adulthood. Moreover, cumulative self-oriented events accounted for a larger percentage of variance in symptom severity compared to events directed at others. CONCLUSION: Our findings suggest that the cumulative impact of exposure to traumatic events throughout the life course contributes significantly to posttraumatic stress in older adulthood above and beyond other known predictors of PTSD.