Migraine Prevalence, Environmental Risk, and Comorbidities in Men and Women Veterans.

Importance: Migraine is a prevalent and debilitating condition that substantially impacts quality of life. Investigating migraine prevalence, associated comorbidities, and potential military service exposures in veterans, focusing on gender differences, is crucial for targeted interventions and management strategies. Objective: To determine the prevalence of migraine, associated health comorbidities, and potential military service and environmental exposures among men and women US veterans using a large-scale epidemiological sample from the Million Veteran Program (MVP). Design, Setting, and Participants: This cross-sectional study analyzed self-report survey data from the MVP, a large epidemiological sample of US veterans that was started in 2011 and has ongoing enrollment. Eligible participants were selected from the MVP database in 2023. The study included 491 604 veterans to examine migraine prevalence, health comorbidities, demographic characteristics, military service history, and environmental exposures. Data were analyzed from December 2022 to July 2023. Exposures: Military service and environmental factors, such as chemical or biological warfare exposure, were considered. Main Outcomes and Measures: The primary outcome was migraine prevalence among men and women veterans, assessed through self-reported diagnoses. Secondary outcomes included the association between migraine and health comorbidities, demographic characteristics, military service history, and environmental exposures. Results: Of the 491 604 veterans included in this study, 450 625 (91.8%) were men and 40 979 (8.2%) were women. The lifetime prevalence of migraine was significantly higher in women (12 324 of 40 979 [30.1%]) than in men (36 816 of 450 625 [8.2%]). Migraine prevalence varied by race and ethnicity, with the highest prevalence in Hispanic or Latinx women (1213 of 3495 [34.7%]). Veterans with migraine reported worse general health, higher levels of pain, increased pain interference with work, a higher likelihood of psychiatric and neurological health conditions, and greater lifetime opioid use. Specific aspects of military service, including service post-September 2001 and deployment in Operation Enduring Freedom and Operation Iraqi Freedom, and environmental factors, including Agent Orange, chemical and biological welfare, and antinerve agent pills history, were significantly associated with migraine prevalence. Conclusions and Relevance: In this cross-sectional study of migraine, the results highlighted gender differences in migraine prevalence and associated health comorbidities among US veterans. The findings emphasized the need for interdisciplinary approaches to migraine management, increased awareness and education efforts, and population-based screening strategies, particularly for women and Hispanic veterans who are at greater risk. Our findings encourage further research into tailored interventions for specific subpopulations and the impact of military service and environmental exposures on migraine and related health conditions.

Genetic architecture distinguishes tinnitus from hearing loss.

Tinnitus is a heritable, highly prevalent auditory disorder treated by multiple medical specialties. Previous GWAS indicated high genetic correlations between tinnitus and hearing loss, with little indication of differentiating signals. We present a GWAS meta-analysis, triple previous sample sizes, and expand to non-European ancestries. GWAS in 596,905 Million Veteran Program subjects identified 39 tinnitus loci, and identified genes related to neuronal synapses and cochlear structural support. Applying state-of-the-art analytic tools, we confirm a large number of shared variants, but also a distinct genetic architecture of tinnitus, with higher polygenicity and large proportion of variants not shared with hearing difficulty. Tissue-expression analysis for tinnitus infers broad enrichment across most brain tissues, in contrast to hearing difficulty. Finally, tinnitus is not only correlated with hearing loss, but also with a spectrum of psychiatric disorders, providing potential new avenues for treatment. This study establishes tinnitus as a distinct disorder separate from hearing difficulties.

Exploring Interactions Between Traumatic Brain Injury History and Gender on Medical Comorbidities in Military Veterans: An Epidemiological Analysis in the VA Million Veteran Program.

Epidemiological studies of medical comorbidities and possible gender differences associated with traumatic brain injury (TBI) are limited, especially among military veterans. The purpose of this study was to examine relationships between TBI history and a wide range of medical conditions in a large, national sample of veterans, and to explore interactions with gender. Participants of this cross-sectional epidemiological study included 491,604 veterans (9.9% TBI cases; 8.3% women) who enrolled in the VA Million Veteran Program (MVP). Outcomes of interest were medical comorbidities (i.e., neurological, mental health, circulatory, and other medical conditions) assessed using the MVP Baseline Survey, a self-report questionnaire. Logistic regression models adjusting for age and gender showed that veterans with TBI history consistently had significantly higher rates of medical comorbidities than controls, with the greatest differences observed across mental health (odds ratios [ORs] = 2.10-3.61) and neurological (ORs = 1.57-6.08) conditions. Similar patterns were found when evaluating men and women separately. Additionally, significant TBI-by-gender interactions were observed, particularly for mental health and neurological comorbidities, such that men with a history of TBI had greater odds of having several of these conditions than women with a history of TBI. These findings highlight the array of medical comorbidities experienced by veterans with a history of TBI, and illustrate that clinical outcomes differ for men and women with TBI history. Although these results are clinically informative, more research is needed to better understand the role of gender on health conditions in the context of TBI and how gender interacts with other social and cultural factors to influence clinical trajectories following TBI. Ultimately, understanding the biological, psychological, and social mechanisms underlying these comorbidities may help with tailoring TBI treatment by gender and improve quality of life for veterans with TBI history.

Genome-wide association study of traumatic brain injury in U.S. military veterans enrolled in the VA million veteran program.

Large-scale genetic studies of traumatic brain injury (TBI) are lacking; thus, our understanding of the influence of genetic factors on TBI risk and recovery is incomplete. This study aimed to conduct a genome-wide association study (GWAS) of TBI in VA Million Veteran Program (MVP) enrollees. Participants included a multi-ancestry cohort (European, African, and Hispanic ancestries; N = 304,485; 111,494 TBI cases, 192,991 controls). TBI was assessed using MVP survey data and International Classification of Diseases (ICD) codes from the Veterans Health Administration's electronic health record. GWAS was performed using logistic regression in PLINK, and meta-analyzed in METAL. FUMA was used for post-GWAS analysis. Genomic structural equation modeling (gSEM) was conducted to investigate underlying genetic associations with TBI, and bivariate MiXeR was used to estimate phenotype specific and shared polygenicity. SNP-based heritability was 0.060 (SE = 0.004, p = 7.83×10-66). GWAS analysis identified 15 genome-wide significant (GWS) loci at p < 5×10-8. Gene-based analyses revealed 14 gene-wide significant genes; top genes included NCAM1, APOE, FTO, and FOXP2. Gene tissue expression analysis identified the brain as significantly enriched, particularly in the frontal cortex, anterior cingulate cortex, and nucleus accumbens. Genetic correlations with TBI were significant for risk-taking behaviors and psychiatric disorders, but generally not significant for the neurocognitive variables investigated. gSEM analysis revealed stronger associations with risk-taking traits than with psychiatric traits. Finally, the genetic architecture of TBI was similar to polygenic psychiatric disorders. Neurodegenerative disorders including Alzheimer's and Parkinson's disease showed much less polygenicity, however, the proportion of shared variance with TBI was high. This first well-powered GWAS of TBI identified 15 loci including genes relevant to TBI biology, and showed that TBI is a heritable trait with comparable genetic architecture and high genetic correlation with psychiatric traits. Our findings set the stage for future TBI GWASs that focus on injury severity and diversity and chronicity of symptom sequelae.

Genomic Structural Equation Modeling Reveals Latent Phenotypes in the Human Cortex with Distinct Genetic Architecture.

Genetic contributions to human cortical structure manifest pervasive pleiotropy. This pleiotropy may be harnessed to identify unique genetically-informed parcellations of the cortex that are neurobiologically distinct from functional, cytoarchitectural, or other cortical parcellation schemes. We investigated genetic pleiotropy by applying genomic structural equation modeling (SEM) to map the genetic architecture of cortical surface area (SA) and cortical thickness (CT) for the 34 brain regions recently reported in the ENIGMA cortical GWAS. Genomic SEM uses the empirical genetic covariance estimated from GWAS summary statistics with LD score regression (LDSC) to discover factors underlying genetic covariance, which we are denoting genetically informed brain networks (GIBNs). Genomic SEM can fit a multivariate GWAS from summary statistics for each of the GIBNs, which can subsequently be used for LD score regression (LDSC). We found the best-fitting model of cortical SA identified 6 GIBNs and CT identified 4 GIBNs. The multivariate GWASs of these GIBNs identified 74 genome-wide significant (GWS) loci (p<5×10-8), including many previously implicated in neuroimaging phenotypes, behavioral traits, and psychiatric conditions. LDSC of GIBN GWASs found that SA-derived GIBNs had a positive genetic correlation with bipolar disorder (BPD), and cannabis use disorder, indicating genetic predisposition to a larger SA in the specific GIBN is associated with greater genetic risk of these disorders. A negative genetic correlation was observed with attention deficit hyperactivity disorder (ADHD), major depressive disorder (MDD), and insomnia, indicating genetic predisposition to a larger SA in the specific GIBN is associated with lower genetic risk of these disorders. CT GIBNs displayed a negative genetic correlation with alcohol dependence. Jointly modeling the genetic architecture of complex traits and investigating multivariate genetic links across phenotypes offers a new vantage point for mapping the cortex into genetically informed networks.

Patterns of adverse childhood experiences and cardiovascular risk factors in U.S. adults.

Adverse Childhood Experiences (ACEs) are associated with poor health yet, we know little about how distinct patterns of ACE types are associated with cardiovascular (cardiovascular (CVD)) risk factors. The current study 1) examined associations of latent ACE classes with modifiable CVD risk factors including high cholesterol, smoking, diabetes, hypertension, high triglycerides, physical inactivity, overweight/obesity, and lifetime depression; and 2) examined the impact of socioeconomic status-related (SES) factors on these relationships. Using a cross-sectional analysis of the National Epidemiologic Survey of Alcohol and Related Conditions-III (n = 36,309) data, four latent classes of ACEs were previously identified: 1) low adversity, 2) primarily household dysfunction, 3) primarily maltreatment, and 4) multiple adversity types. We examined the association of these classes with CVD risk factors in adulthood and subsequently, the same model accounting for SES-related factors. Tobacco smoking, overweight/obesity, and lifetime depression were each associated with higher odds of being in classes 2, 3, and 4 than class 1, respectively. These relationships held after adjusting for SES-related factors. Class 4 was associated with the most CVD risk factors, including high triglycerides and high cholesterol after controlling for SES-related factors. The consistent associations between tobacco smoking, overweight/obesity, and lifetime depression with each adverse ACE profile, even after controlling for SES, suggest behavioural CVD prevention programs should target these CVD risk factors simultaneously.

Confirmatory Factor Analysis of the Comprehensive Assessment of Acceptance and Commitment Therapy (CompACT) in Active-Duty Military Personnel.

Acceptance and Commitment Therapy (ACT) is a third-wave cognitive-behavioral treatment that targets psychological flexibility (PF), or the ability to persist in behavior consistent with values regardless of unwanted private experiences. The growing use of ACT necessitates an accurate assessment of PF. The Comprehensive Assessment of Acceptance and Commitment Therapy (CompACT) is a three-factor measure of PF (Openness to Experience, Valued Action, and Behavioral Awareness) whose psychometric properties have been examined in limited populations. The current study examined the factor structure and psychometric properties of the CompACT in U.S. military personnel who enrolled in a weight management randomized controlled trial. Military personnel who either failed or were at risk of failing the Navy's physical fitness assessment or had overweight/obese body mass index (BMI; N = 178, Mage = 29.15 years; MBMI = 33.13 kg/m2; 61.8% female) completed the CompACT and other questionnaires. Confirmatory factor analysis was used to evaluate the three-factor structure of the original 23-item CompACT (CompACT-23) as well as an 18-item version identified in a Portuguese sample (CompACT-18). Internal consistency and convergent validity with measures of weight-related experiential avoidance, perceived stress, anxiety, depression, PTSD symptoms, and life satisfaction were examined. The three-factor structure of the CompACT-23 showed poor fit to the data while the fit of the CompACT-18 was acceptable, as indicated by three descriptive indices (χ2/df = 1.73, RMSEA = 0.069, SRMR = 0.074). All descriptive fit indices in addition to two comparative fit indices (AIC and BIC) indicated improved model fit over the CompACT-23. The CompACT-18 and its subscales exhibited adequate internal consistency (α = 0.768 to 0.861) and convergent validity in expected directions with measures of weight-related experiential avoidance, perceived stress, anxiety, depression, PTSD symptoms, and satisfaction with life. Results support using the refined, English language CompACT-18 as a three-factor measure of PF in populations such as U.S. military personnel who may benefit from weight management intervention. Future research should explore the content validity of the full measure and the removed items. Lost content could mean the CompACT-23 and the CompACT-18 differentially assess PF. Additional studies should examine psychometric properties in large and more diverse samples to further evaluate the appropriateness of the measure across populations. Longitudinal studies are needed to examine test-retest reliability and sensitivity to change.

Latent Class Patterns of Adverse Childhood Experiences and Their Relationship to Veteran Status and Sex in the National Epidemiologic Survey of Alcohol and Related Conditions Wave III.

INTRODUCTION: Adverse childhood experiences (ACEs) are associated with poor psychosocial and health outcomes in adulthood. Veterans and females experience ACEs disproportionately. A greater understanding of this disparity may be achieved by examining the relationship between distinct ACE patterns and these demographic characteristics. Therefore, this study examined distinct ACE patterns and their association with Veteran status, sex, and other demographics in a nationally representative sample of U.S. adults to inform interventions tailored to ACE patterns experienced by specific groups. MATERIALS AND METHODS: Latent class analysis (LCA) was conducted with data from the National Epidemiologic Survey of Alcohol and Related Conditions-III, a nationally representative structured diagnostic interview conducted from 2012-2013. The target population was the noninstitutionalized adult population living in the USA. The analytic sample was 36,190 (mean age 46.5 years; 48.1% male). Of these participants, 3,111 were Veterans. Data were analyzed between September 2020 and January 2021. RESULTS: Latent class analysis revealed a four-class solution: (1) "Low adversity" (75.3%); (2) "Primarily household dysfunction" (9.0%); (3) "Primarily maltreatment" (10.7%); and (4) "Multiple adversity types" (5.1%). Compared to "Low adversity," members in the other classes were more likely to be Veterans (odds ratio (OR)C2vC1 = 1.33, ORC3vC1 = 1.55, ORC4vC1 = 1.98) and female (ORC2vC1 = 1.58, ORC3vC1 = 1.22, ORC4vC1 = 1.65). While lower education and income were also related to higher adversity class membership, Veteran status and sex were the strongest predictors, even when controlling for education and income. CONCLUSIONS: Distinct and meaningful patterns of ACEs identified in this study highlight the need for routine ACE screenings in Veterans and females. As in the current study, operationalizing and clustering ACEs can inform screening measures and trauma-informed interventions in line with personalized medicine. Future work can test if classes are differentially associated with health outcomes.

Technology-supported Acceptance and Commitment Therapy for chronic health conditions: A systematic review and meta-analysis.

Chronic health conditions (CHCs) are common and associated with functional limitations. Acceptance and commitment therapy (ACT) shows promise in improving functioning, quality of life, and distress across several CHCs. The purpose of this study was to conduct a systematic review of technology-supported ACT for CHCs and perform a meta-analysis on functioning and ACT process outcomes. Multiple databases were systematically searched for randomized controlled trials. A total of 20 unique studies with 2,430 randomized participants were included. CHCs addressed in these studies were chronic pain (k = 9), obesity/overweight (k = 4), cancer (k = 3), hearing loss (k = 1), HIV (k = 1), multiple sclerosis (k = 1), and tinnitus (k = 1). Internet and telephone were the most used technology platforms. All studies included therapist contact with considerable heterogeneity between studies. Random effects meta-analyses found medium effect sizes showing technology-supported ACT outperformed comparator groups on measures of function at post-treatment (Hedges' g = -0.49; p = 0.002) and follow-up (Hedges' g = -0.52; p = 0.02), as well as ACT process outcomes at post-treatment (Hedges' g = 0.48; p < 0.001) and follow-up (Hedges' g = 0.44; p < 0.001). Technology-supported ACT shows promise for improving function and ACT process outcomes across a range of CHCs. Recommendations are provided to optimize technology-supported ACT for CHCs. PROSPERO registration number: CRD42020200230.

Pain and Trauma: The Role of Criterion A Trauma and Stressful Life Events in the Pain and PTSD Relationship.

Chronic pain and post-traumatic stress disorder (PTSD) frequently co-occur, and research suggests that these 2 conditions exacerbate one another producing greater impact on normal functioning in combination than separately. The influence of traumatic experiences on both pain and PTSD has been shown, but the nature of this interplay remains unclear. Although Criterion A trauma is required for the diagnosis of PTSD, whether the association between PTSD and chronic pain is dependent on Criterion A is underexplored. In this observational cohort study, we examined the association between pain and PTSD-like symptoms in the context of Criterion A trauma in 5,791 men from the Vietnam Era Twin Registry. Correlations and mixed-effects regression models were used to evaluate the relationship between PTSD Checklist-Civilian Version symptoms and multiple indicators of pain from the Short Form McGill Pain Questionnaire across trauma history and chronic pain conditions. 53.21% of the participants experienced trauma consistent with DSM-IV Criterion A for PTSD. The associations between pain indicators and PTSD-like symptoms was stronger for individuals with a history of trauma but remained robust for individuals without trauma history. Small but significant interactions between past trauma and pain indicators and PTSD-like symptoms were observed. Findings were similar in a subsample of participants with history of chronic pain conditions. The relationship between PTSD-like symptoms and indicators of pain were largely independent of trauma consistent with Criterion A, highlighting the need to better understand and address stressful life events in chronic pain patients and pain concerns in individuals reporting trauma. PERSPECTIVE: This article demonstrates that the relationship between PTSD-like symptoms and indicators of pain is largely independent of trauma consistent with Criterion A. This finding highlights the need to better understand and address stressful life events in chronic pain patients and pain concerns in individuals reporting trauma.

Genetic and environmental influences on posttraumatic stress disorder symptoms and disinhibited eating behaviors.

Posttraumatic stress disorder (PTSD) and eating disorders (ED) frequently co-occur, but the mechanisms underlying this association remain unclear. EDs are characterized by features of maladaptive eating behaviors including disinhibited eating and cognitive dietary restraint. Identifying the genetic overlap between PTSD symptoms and maladaptive eating behaviors may elucidate biological mechanisms and potential treatment targets. A community sample of 400 same-sex twins (102 monozygotic and 98 dizygotic pairs) completed the PTSD Checklist-Civilian (PCL-C) for PTSD symptoms and the Three-Factor Eating Questionnaire-Reduced (TFEQ-R18) for eating behaviors (uncontrolled eating, emotional eating, and cognitive dietary restraint). We used biometric modeling to examine the genetic and environmental relationships between PCL-C and TFEQ-R18 total and subscales scores. Heritability was estimated at 48% for PTSD symptoms and 45% for eating behavior overall. Bivariate models revealed a significant genetic correlation between PTSD symptoms and eating behavior overall (rg =.34; CI:.07,.58) and Uncontrolled Eating (rg =.53; CI:.24,.84), and a significant environmental correlation between PTSD symptoms and Emotional Eating (re =.30; CI:.12,.45). These findings suggest the influence of common etiology. Future research and clinical efforts should focus on developing integrated treatments.

Posttraumatic Stress Disorder and Chronic Pain Conditions in Men: A Twin Study.

OBJECTIVE: Posttraumatic stress disorder (PTSD) is highly comorbid with chronic pain conditions that often co-occur such as migraine headaches, temporomandibular disorder, irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, chronic prostatitis/chronic pelvic pain syndrome, and tension headaches. Using a genetically informative sample, the current study evaluated the genetic and environmental factors contributing to the co-occurrence of PTSD and chronic pain conditions. METHODS: Data from 4680 male twins in the Vietnam Era Twin Registry were examined. Biometric modeling was used to estimate genetic and environmental variance components and genetic and environmental correlations between PTSD and multiple chronic pain conditions. RESULTS: Heritabilities were estimated at 43% (95% confidence interval [CI] = 15%-63%) for PTSD and 34% (95% CI = 27%-41%) for the combined history of any one or more pain condition. Specific pain condition heritabilities ranged from 15% (95% CI = 0%-48%) for tension headaches to 41% (95% CI = 27%-54%) for migraine headaches. Environmental influences accounted for the remaining variance in pain conditions. The genetic correlation between PTSD and combined history of any one or more pain condition was rg= 0.61 (95% CI = 0.46-0.89) and ranged for individual pain conditions from rg= 0.44 (95% CI = 0.24-0.77) for migraine headache to rg= 0.75 (95% CI = 0.52-1.00) for tension headaches. CONCLUSIONS: PTSD and chronic pain conditions are highly comorbid, and this relationship can be explained by both genetic and environmental overlap. The precise mechanisms underlying these relationships are likely diverse and multifactorial.

Confirmatory Factor Analysis of the Acceptance and Action Questionnaire for Weight-Related Difficulties-Revised (AAQW-R) in a United States Sample of Adults with Overweight and Obesity.

OBJECTIVE: To examine the psychometric properties of the English language version of the 10-item Acceptance and Action Questionnaire for Weight-Related Difficulties-Revised (AAQW-R) in a United States (U.S.) sample of women and men with overweight/obesity (OW/OB). METHOD: Adults with OW/OB seeking weight loss (N = 283; 59% women) completed the AAQW-R and other weight-related and psychosocial measures. Confirmatory factor analysis was used to examine single-factor, three-factor, and second-order factor structures of the AAQW-R, which were previously examined in a sample of Portuguese women. A chi-square difference test was used to compare the fit of a single-factor structure with three-factor and second-order factor structures. Internal reliability and convergent validity were examined for the total and three-factor subscale scores. RESULTS: The single-factor structure evidenced poor fit to the data whereas the three-factor structure evidenced acceptable fit. The second-order structure was assessed qualitatively due to limitations to statistical model specification. The internal reliability of the AAQW-R total score and each of the three subscales were in the good and acceptable ranges, respectively. Total and subscale scores demonstrated good convergent validity. DISCUSSION: Findings suggest that the English language version of the AAQW-R can be used to assess weight-related experiential avoidance in U.S. adult samples with OW/OB as a three-factor construct (food as control, weight as a barrier to living, weight stigma), with or without a total score. Additional research should confirm measurement invariance among various sociodemographic groups.

A MAPP Network Case-control Study of Urological Chronic Pelvic Pain Compared With Nonurological Pain Conditions.

OBJECTIVES: Limited research suggests commonalities between urological chronic pelvic pain syndromes (UCPPS) and other nonurological chronic overlapping pain conditions (COPCs) including fibromyalgia, chronic fatigue syndrome, and irritable bowel syndrome. The goal of this case-control study was to examine similarities and differences between UCPPS and these other COPCs. MATERIALS AND METHODS: As part of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research (MAPP) Network, we examined 1039 individuals with UCPPS (n=424), nonurological COPCs (n=200), and healthy controls (HCs; n=415). Validated standardized measures were used to assess urological symptoms, nonurological pain symptoms, and psychosocial symptoms and traits. RESULTS: Participants with UCPPS had more urological symptoms than nonurological COPCs or HCs (P<0.001); nonurological COPC group also had significantly worse urological symptoms than HCs (P<0.001). Participants with nonurological COPCs reported more widespread pain than those with UCPPS (P<0.001), yet both groups had similarly increased symptoms of anxiety, depression, negative affect, perceived stress, neuroticism, and lower levels of extraversion than HCs (P<0.001). Participants with UCPPS with and without COPCs reported more catastrophizing than those with nonurological COPCs (P<0.001). DISCUSSION: Findings are consistent with the hypothesis of common underlying biopsychosocial mechanisms and can guide the comprehensive assessment and treatment of these conditions regardless of the primary site of pain or diagnosis. Heightened catastrophizing in UCPPS should be examined to inform psychosocial interventions and improve patient care.

Improvement in 6-min Walk Test Distance Following Treatment for Behavioral Weight Loss and Disinhibited Eating: an Exploratory Secondary Analysis.

BACKGROUND: Poor functional exercise capacity is common among those with obesity; however, objective measures of exercise capacity are rarely examined in behavioral treatments targeting obese individuals. We examined whether a 4-week acceptance and commitment therapy (ACT) intervention for disinhibited eating or a behavioral weight loss (BWL) intervention improved exercise capacity and explored demographic and disinhibited eating variables related to exercise capacity. METHODS: Veterans (n = 61), randomized to receive ACT or BWL, completed an assessment of exercise capacity via the 6-min walk test (6MWT) at baseline and 6-month follow-up. Measures of disinhibited eating patterns and body mass index (BMI), at baseline and post-treatment, were also collected. Change in 6MWT distance and treatment group differences were examined using mixed ANOVAs. Characteristics related to baseline 6MWT and predictors of improvement in 6MWT at 6 months were examined with hierarchical multiple regression. RESULTS: There were overall significant improvements on the 6MWT from baseline to 6-month follow-up (F(1,59) = 11.14, p = .001, ηp2 = .159) but no differences between the ACT and BWL groups. Baseline BMI (ß = - .33, p = .005) was the only variable related to baseline 6MWT. Improvements on the 6MWT were related to younger age (ß = - .41, p = 0.001), female gender (ß = .36, p = .001), and treatment-related increases in dietary restraint behaviors (ß = .42, p = .001). CONCLUSIONS: Functional exercise capacity improved among participants completing behavioral interventions for weight and disinhibited eating. Improvements in dietary behavior regulatory skills may have generalized to improved regulation in other behavioral domains associated with exercise capacity.

Genetic and Environmental Influences on Urinary Conditions in Men: A Classical Twin Study.

OBJECTIVE: To evaluate the genetic and environmental relationship among prostatitis and other urological conditions, including benign prostatic hyperplasia (BPH) and prostate cancer (CaP), a classical twin design and biometric modeling was used. While prostatitis-characterized by pain and voiding symptoms, no clear etiology, and functional and quality of life impairments-co-occurs with other urinary conditions, the degree of shared overlapping etiologic processes among them remains unclear. We examined the contribution of genetic and environmental factors to these conditions and the etiology of their associations at the level of genetic and environmental influences. METHODS: 4380 monozygotic and dizygotic male twin pairs from the Vietnam Era Twin Registry reported lifetime physician-diagnosed prostatitis (combined acute and chronic), bladder problems, enlarged prostate/BPH, and CaP. Multivariate biometrical modeling estimated the magnitude of genetic and environmental influences for each condition, as well as their genetic and environmental covariance. The common pathway model tested the assumption that covariation among these urinary conditions is determined by a single latent factor. RESULTS: Overall prevalence of prostatitis was 2.7%. Heritability estimates ranged from 19% for bladder problems to 42% for CaP. Significant shared environmental influences were present for CaP (12%), enlarged prostate/BPH (10%) but were smaller than genetic influences. A reduced one factor common pathway model provided the best fit, suggesting that covariation among the conditions is determined by a shared latent factor. CONCLUSION: We identified a common, genetically-influenced factor that accounts for much of the comorbidity among these 4 disease conditions. Nonshared environmental factors also make a significant contribution.

Chronic prostatitis and comorbid non-urological overlapping pain conditions: A co-twin control study.

OBJECTIVES: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is characterized by pain and voiding symptoms in the absence of an obvious infection or other cause. CP/CPPS frequently occurs with non-urological chronic overlapping pain conditions (COPCs) of unknown etiology. We conducted a co-twin control study in men discordant for chronic prostatitis (CP), an overarching diagnosis of which approximately 90% is CP/CPPS. The primary aim was to investigate the contribution of familial factors, including shared genetic and common environmental factors, to the comorbidity of CP and COPCs. METHODS: Data from 6824 male twins in the Vietnam Era Twin Registry were examined to evaluate the association between self-reported lifetime physician diagnosis of CP with COPCs including fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, temporomandibular disorder, tension headaches, and migraine headaches. Random effects logistic regression models were used and within-pair analyses evaluated confounding effects of familial factors on the associations. RESULTS: There were significant associations between CP and all 6 examined COPCs. After adjusting for shared familial influences in within twin pair analyses, the associations for all COPCs diminished but remained significant. Familial confounding was strongest for the association of CP with fibromyalgia and temporomandibular disorder and smallest for irritable bowel syndrome. CONCLUSIONS: CP and COPCs are highly comorbid. These associations can be partially explained by familial factors. The mechanisms underlying these relationships are likely diverse and multifactorial. Future longitudinal research can help to further elucidate specific genetic and environmental mechanisms and determine potentially causal relationships between CP and its comorbidities.

Genetic and Environmental Influences on Sleep, Pain, and Depression Symptoms in a Community Sample of Twins.

OBJECTIVE: We used quantitative genetic methods to evaluate whether sleep quality, pain, and depression symptoms share a common genetic diathesis, to estimate the genetic and environmental sources of covariance among these symptoms, and to test for possible causal relationships. METHODS: A community sample of 400 twins from the University of Washington Twin Registry completed standardized self-report questionnaires. We used biometric modeling to assess genetic and environmental contribution to the association between sleep quality measured by the Pittsburgh Sleep Quality Index, pain measured by the Brief Pain Inventory, and depression symptoms measured by the Brief Symptom Inventory. Trivariate Cholesky structural equation models were used to decompose correlations among the phenotypes. RESULTS: Heritability was estimated at 37% (95% confidence interval = 20%-51%) for sleep quality, 25% (9%-41%) for pain, and 39% (22%-53%) for depression. Nonshared environmental influences accounted for the remaining variance. The genetic correlation between sleep quality and pain had an rg value of .69 (95% confidence interval [CI] = 0.33-0.97), rg value of .56 (95% CI = 0.55-0.98) between pain and depression, and rg value of .61 (95% CI = 0.44-0.88) between depression and sleep quality. Nonshared environmental overlap was present between pain and sleep quality as well as depression and sleep quality. CONCLUSIONS: The link between sleep quality, pain, and depression was primarily explained by shared genetic influences. The genetic factors influencing sleep quality and pain were highly correlated even when accounting for depression. Findings support the hypothesis of a genetic link between depression and pain as well as potential causality for the association of sleep quality with pain and depression.

Heritability of Lower Urinary Tract Symptoms in Men: A Twin Study.

PURPOSE: Symptoms of urinary irritation, urgency, frequency and obstruction, known as lower urinary tract symptoms, are common in urological practice. However, little is known about the etiology or pathogenesis of lower urinary tract symptoms, especially the relative contributions of genetic and environmental factors to the development of these symptoms. We used a classic twin study design to examine the relative contributions of genetic and environmental factors to the occurrence of lower urinary tract symptoms in middle-aged men. MATERIALS AND METHODS: Twins were members of the Vietnam Era Twin Registry. We used a mail survey to collect data on lower urinary tract symptoms using the I-PSS (International Prostate Symptom Score) instrument. Twin correlations and biometric modeling were used to determine the relative genetic and environmental contributions to variance in I-PSS total score and individual items. RESULTS: Participants were 1,002 monozygotic and 580 dizygotic middle-aged male twin pairs (mean age 50.2 years, SD 3.0). Nearly 25% of the sample had an I-PSS greater than 8, indicating at least moderate lower urinary tract symptoms. The heritability of the total I-PSS was 37% (95% CI 32-42). Heritability estimates ranged from 21% for nocturia to 40% for straining, with moderate heritability (34% to 36%) for urinary frequency and urgency. CONCLUSIONS: Genetic factors provide a moderate contribution (20% to 40%) to lower urinary tract symptoms in middle-aged men, suggesting that environmental factors may also contribute substantially to lower urinary tract symptoms. Future research is needed to define specific genetic and environmental mechanisms that underlie the development of these symptoms and conditions associated with lower urinary tract symptoms.