Survival of veterans treated with enzalutamide and abiraterone for metastatic castrate resistant prostate cancer based on comorbid diseases.

BACKGROUND: Comorbid diseases influence patient outcomes, yet little is known about how comorbidities interact with treatments for metastatic castrate-resistant prostate cancer (mCRPC). No head-to-head trials have compared the efficacy of abiraterone and enzalutamide - oral androgen-receptor targeted agents (ARTAs) for mCRPC. In patients with comorbid disease, outcomes with ARTAs may differ due to disparate mechanisms of action, adverse events, and drug interactions. METHODS: Retrospective observational study of US veterans initiating treatment for mCRPC with abiraterone or enzalutamide between September 2014 and June 2017. Treatment duration and overall survival (OS) was compared based on age and comorbid diseases. The association between ARTA and OS was assessed using Cox proportional hazards and propensity-score matched modeling while adjusting for potential confounders. Sensitivity analyses were performed based on patient age, comorbidities, and subsequent treatments for mCRPC. RESULTS: Of 5822 veterans treated for mCRPC, 43.0% initially received enzalutamide and 57.0% abiraterone. Veterans initially treated with enzalutamide versus abiraterone were older (mean 75.8 vs. 75.0 years) with higher mean Charlson comorbidity index (4.4 vs. 4.1), and higher rates of cardiovascular disease or diabetes (74.2% vs. 70.6%). In the entire population, veterans initially treated with enzalutamide had longer median OS compared to those initially treated with abiraterone (24.2 vs. 22.1 months, p = 0.001). In veterans with cardiovascular disease or diabetes, median treatment duration with enzalutamide was longer (11.4 vs. 8.6 months, p < 0.001) with longer median OS compared to abiraterone (23.2 vs. 20.5 months, p < 0.001). In a propensity score matched cohort, enzalutamide was associated with decreased mortality compared to abiraterone (HR 0.90, 95% CI 0.84-0.96). CONCLUSIONS: Veterans with cardiovascular disease or diabetes had longer treatment duration and OS with enzalutamide compared to abiraterone. Further study of ARTA selection may benefit men with metastatic castrate resistant prostate cancer and likely hormone sensitive prostate cancer, especially among patients with comorbid diseases.

A cohort study of neuropsychological functioning in spouses of U.S. Gulf War veterans.

AIMS: Veterans of the 1991 Gulf War reported symptoms in their spouses that mirrored veterans' symptoms following their return from the war, including problems with attention and memory. Neuropsychological functioning in these spouses has not been examined with objective tests. This study sought to determine if these spouses exhibited deficits in neuropsychological functioning. MAIN METHODS: Spouses of a national cohort of 1991 Gulf War deployed (n = 470) and non-deployed veterans (n = 524) were examined with neuropsychological tests in 1999-2001. KEY FINDINGS: Neuropsychological tests were factor analyzed yielding five factors: verbal memory, visual memory, attention/working memory, visual organization, and motor speed. Spouses of deployed and nondeployed veterans did not differ on mean factor scores, percentage of impaired factors, or individual test scores. Spouse attention/working memory was related to their having diagnoses of PTSD or anxiety disorders, or self-reported symptoms of current anxiety. Spouse visual memory was related to a diagnosis of current depression. Spouse motor speed was related to their own status of having chronic multisymptom illness (CMI). SIGNIFICANCE: Spouses of Gulf War deployed and nondeployed veterans demonstrated similar neuropsychological functioning, although spouses with psychiatric diagnoses and symptoms, or CMI demonstrated neuropsychological impairments characteristic of those conditions, suggesting that monitoring spouses for these conditions and impairments may be warranted. This pattern of relative weaknesses mirrors some of the previously reported findings for Gulf War veterans, although the veterans displayed neuropsychological impairments beyond what was accounted for by these conditions.

Cognitive dysfunction among people with systemic lupus erythematosus is associated with reduced participation in daily life.

OBJECTIVES: This study aimed to investigate the distribution of cognitive function in people with systemic lupus erythematosus (SLE) by objective and self-report measures and associations between cognition and participation among people with SLE. METHODS: Fifty-five volunteers with SLE (age: 39.7 ± 12.7yrs, female: 92.7%) completed the Montreal Cognitive Assessment (MoCA) to measure cognitive ability objectively, the Cognitive Symptom Inventory (CSI) and PROMIS Cognitive Function 8a (CF) to assess self-reported everyday cognition, and PROMIS-43 Profile to assess self-reported ability to participate in social roles and activities (participation) and other disease-associated symptoms (e.g., depression, pain, fatigue). RESULTS: The average MoCA score was 25.3 ± 3.1, with 47.3% of participants scoring <26, which is indicative of cognitive impairment. Group average CSI (35.8 ± 7.9), CF (T-score = 45.0 ± 8.5), and participation (T-score = 46.9 ± 11.2) scores suggest mildly impaired functional cognition and participation compared to normative data. Participation correlated with self-reported everyday cognition measures (r ≥ 0.56, p < 0.01) but not with MoCA (r = 0.25, p = 0.06). In hierarchical linear regression analysis, CSI, fatigue, and pain were each significant independent predictors of participation (R2 = 0.78, p < 0.01). CONCLUSIONS: We found that cognitive dysfunction is common among people with SLE. Along with pain and fatigue, reduced everyday cognitive function contributes to reduced participation in social, leisure, work, and family-related activities.

Mental health in spouses of U.S. Gulf War veterans.

Veterans' spouses are at risk for mental distress and substance use. We examined long term psychological functioning in spouses from a national cohort of 1991 Gulf War era veterans. From clinical interviews, spouses of deployed veterans (n = 488) did not have a greater prevalence of post-war mental disorders compared to spouses of non-deployed veterans (n = 536); however, in couples that were living together since the war, there was an increased risk of anxiety disorders or any one disorder. On questionnaires, the impact varied but was most consistently observed in more severe depression and greater functional impairment in spouses of deployed compared to non-deployed veterans. If a veteran developed post-war anxious/depressive disorders or any one mental disorder, the matched spouse was more likely to develop post-war anxious/depressive disorders or any one mental disorder, respectively. Veteran combat exposure did not similarly increase the risk of spouse post-war mental disorders. Greater spouse self-reported symptomatology was observed in spouses of veterans with anxious/depressive disorders even when controlling for deployment. In summary, the war conferred greater risk for spouse mental disorders and distress for spouses of veterans with mental health disorders, with some increased risk for spouses of deployed veterans, especially in couples together since the war.

Evaluating the Productivity of VA, NIH, and AHRQ Health Services Research Career Development Awardees.

PURPOSE: To evaluate the academic advancement and productivity of Department of Veterans Affairs Health Services Research and Development (HSR&D) Career Development Award (CDA) program recipients, National Institutes of Health (NIH) K awardees in health services research (HSR), and Agency for Healthcare Research and Quality (AHRQ) K awardees. METHOD: In all, 219 HSR&D CDA recipients from fiscal year (FY) 1991 through FY2010; 154 NIH K01, K08, and K23 awardees FY1991-FY2010; and 69 AHRQ K01 and K08 awardees FY2000-FY2010 were included. Most data were obtained from curricula vitae. Academic advancement, publications, grants, recognition, and mentoring were compared after adjusting for years since award, and personal characteristics, training, and productivity prior to the award. RESULTS: No significant differences emerged in covariate-adjusted tenure-track academic rank, number of grants as primary investigator (PI), major journal articles as first/sole author, Hirsch h-index scores, likelihood of a journal editorship position or membership in a major granting review panel, or mentoring postgraduate researchers between the HSR&D CDA and NIH K awardees from FY1991-FY2010, or among the three groups of awardees from FY2000 or later. Among those who reported grant funding levels, HSR&D CDAs from FY1991-2010 had been PI on more grants of $100,000 than NIH K awardees. HSR&D CDAs had a higher mean number of major journal articles than NIH K awardees from FY1991-2010. CONCLUSIONS: Findings show that all three HSR career development programs are successfully selecting and mentoring awardees, ensuring additional HSR capacity to improve the quality and delivery of high-value care.

Tumor Necrosis Factor Inhibition and Head and Neck Cancer Recurrence and Death in Rheumatoid Arthritis.

The objective of this retrospective cohort study was to determine the effect of tumor necrosis factor inhibitor (TNFi) therapy on the risk of head and neck cancer (HNC) recurrence or HNC-attributable death in patients with rheumatoid arthritis (RA). RA patients with HNC were assembled from the US national Veterans' Affairs (VA) administrative databases, and diagnoses confirmed and data collected by electronic medical record review. The cohort was divided into those treated with non-biologic disease-modifying anti-rheumatic drugs (nbDMARDs) versus TNF inhibitors (TNFi) after a diagnosis of HNC. Likelihood of a composite endpoint of recurrence or HNC-attributable death was determined by Cox proportional hazards regression. Of 180 patients with RA and HNC, 31 were treated with TNFi and 149 with nbDMARDs after the diagnosis of HNC. Recurrence or HNC-attributable death occurred in 5/31 (16.1%) patients in the TNFi group and 44/149 (29.5%) patients in the nbDMARD group (p = 0.17); it occurred in 2/16 (13%) patients who received TNFi in the year prior to HNC diagnosis but not after. Overall stage at diagnosis (p = 0.03) and stage 4 HNC (HR 2.49 [CI 1.06-5.89]; p = 0.04) were risk factors for recurrence or HNC-attributable death; treatment with radiation or surgery was associated with a lower risk (HR 0.35 [CI 0.17-0.74]; p = 0.01 and HR 0.39 [CI 0.20-0.76]; p = 0.01 respectively). Treatment with TNFi was not a risk factor for recurrence or HNC-attributable death (HR 0.75; CI 0.31-1.85; p = 0.54). We conclude that treatment with TNFi may be safe in patients with RA and HNC, especially as the time interval between HNC treatment and non-recurrence increases. In this study, TNF inhibition was not associated with an increase in recurrence or HNC-attributable death.

Associations between obsessive-compulsive classes and pathological gambling in a national cohort of male twins.

IMPORTANCE: Because of shared characteristics, pathological gambling (PG) has been variously conceptualized as an obsessive-compulsive (OC) spectrum disorder or as an addictive disorder. Prior community-based studies have not systematically determined the association between PG and OC features and whether common genetic factors contribute to both conditions. OBJECTIVE: To examine the association and genetic correlation between PG and OC features. DESIGN, SETTING, AND PARTICIPANTS: We performed a latent class analysis (LCA) of OC features, cross-sectional tests of association, and classic twin genetic analysis using results of telephone interviews conducted from March 2002 through November 2003. Participants included 1675 male twin pairs from the Vietnam Era Twin Registry, aged 45 to 60 years. MAIN OUTCOMES AND MEASURES: Ten OC features were queried and used to derive OC classes identified via LCA. RESULTS: The best-fitting LCA model identified the following 4 OC classes: unaffected (class 1), ritual/symmetry compulsions (class 2), germ/contamination obsessions (class 3), and severe OC (class 4). All PG symptoms were more common in class 4 OC and 6 of 10 PG symptoms were significantly more common in class 4 OC (P < .01). Participants in the severe class were most likely to have 4 or more DSM-IV or DSM-5 PG diagnostic criteria (odds ratio, 3.8 [95% CI, 1.8-8.2]). The genetic correlation between phenotypes was 0.44 (95% CI, 0.16-0.75). CONCLUSIONS AND RELEVANCE: The association between OC features and diagnostic criteria for PG highlights a role of obsessions and compulsivity in PG, and the lifetime co-occurrence of these disorders results in part from common genetic variance. Phenotypic and genetic overlap between OC features and PG add to our understanding of the most appropriate classification of PG and offers insights for treatment development.

Myocardial infarction risk among patients with fractures receiving bisphosphonates.

OBJECTIVE: To determine if bisphosphonates are associated with reduced risk of acute myocardial infarction (AMI). PATIENTS AND METHODS: A cohort of 14,256 veterans 65 years or older with femoral or vertebral fractures was selected from national administrative databases operated by the US Department of Veterans Affairs and was derived from encounters at Veterans Affairs facilities between October 1, 1998, and September 30, 2006. The time to first AMI was assessed in relationship to bisphosphonate exposure as determined by records from the Pharmacy Benefits Management Database. Time to event analysis was performed using multivariate Cox proportional hazards regression. An adjusted survival analysis curve and a Kaplan-Meier survival curve were analyzed. RESULTS: After controlling for atherosclerotic cardiovascular disease risk factors and medications, bisphosphonate use was associated with an increased risk of incident AMI (hazard ratio, 1.38; 95% CI, 1.08-1.77; P=.01). The timing of AMI correlated closely with the timing of bisphosphonate therapy initiation. CONCLUSION: Our observations in this study conflict with our hypothesis that bisphosphonates have antiatherogenic effects. These findings may alter the risk-benefit ratio of bisphosphonate use for treatment of osteoporosis, especially in elderly men. However, further analysis and confirmation of these findings by prospective clinical trials is required.

Environmental factors selectively impact co-occurrence of problem/pathological gambling with specific drug-use disorders in male twins.

AIMS: Multiple forms of drug abuse/dependence frequently co-occur with problem/pathological gambling (PPG). The current study examines the extent to which genetic and environmental factors contribute to their co-occurrence. DESIGN: Bivariate models investigated the magnitude and correlation of genetic and environmental contributions to problem/pathological gambling and its co-occurrence with nicotine dependence, cannabis abuse/dependence and stimulant abuse/dependence. SETTING: Computer-assisted telephone interviews in the community. PARTICIPANTS: Participants were 7869 male twins in the Vietnam Era Twin Registry, a USA-based national twin registry. MEASUREMENTS: Life-time DSM-III-R diagnoses for problem/pathological gambling, nicotine dependence, cannabis abuse/dependence and stimulant abuse/dependence were determined using the Diagnostic Interview Schedule. FINDINGS: All drug-use disorders displayed additive genetic and non-shared environmental contributions, with cannabis abuse/dependence also displaying shared environmental contributions. Both genetic [genetic correlation rA = 0.22; 95% confidence interval (CI) = 0.10-0.34] and non-shared environmental components (environmental correlation rE = 0.24; 95% CI = 0.10-0.37) contributed to the co-occurrence of problem/pathological gambling and nicotine dependence. This pattern was shared by cannabis abuse/dependence (rA = 0.32; 95% CI = 0.05-1.0; rE = 0.36; 95% CI = 0.16-0.55) but not stimulant abuse/dependence (SAD), which showed only genetic contributions to the co-occurrence with problem/pathological gambling (rA = 0.58; 95% CI = 0.45-0.73). CONCLUSIONS: Strong links between gambling and stimulant-use disorders may relate to the neurochemical properties of stimulants or the illicit nature of using 'hard' drugs such as cocaine. The greater contribution of environmental factors to the co-occurrence between problem/pathological gambling and 'softer' forms of drug abuse/dependence (cannabis, tobacco) suggest that environmental interventions (perhaps relating to availability and legality) may help to diminish the relationship between problem/pathological gambling and tobacco- and cannabis-use disorders.

Longitudinal health study of US 1991 Gulf War veterans: changes in health status at 10-year follow-up.

The authors assessed changes in the health status of US 1991 Gulf War-era veterans from a 1995 baseline survey to a 2005 follow-up survey, using repeated measurement data from 5,469 deployed Gulf War veterans and 3,353 nondeployed Gulf War-era veterans who participated in both surveys. Prevalence differences in health status between the 2 surveys were estimated for adverse health indices and chronic diseases for each veteran group. Persistence risk ratios and incidence risk ratios were calculated after adjustment for demographic and military service characteristics through Mantel-Haenszel stratified analysis. At 10-year follow-up, deployed veterans were more likely to report persistent poor health, as measured by the health indices (functional impairment, limitation of activities, repeated clinic visits, recurrent hospitalizations, perception of health as fair or poor, chronic fatigue syndrome-like illness, and posttraumatic stress disorder), than nondeployed veterans. Additionally, deployed veterans were more likely to experience new onset of adverse health (as measured by the indices) and certain chronic diseases than were nondeployed veterans. During the 10-year period from 1995 to 2005, the health of deployed veterans worsened in comparison with nondeployed veterans because of a higher rate of new onset of various health outcomes and greater persistence of previously reported adverse health on the indices.

Shared genetic contributions to anxiety disorders and pathological gambling in a male population.

BACKGROUND: Pathological gambling (PG) frequently co-occurs with anxiety disorders. However, the extent to which the co-occurrence is related to genetic or environmental factors across PG and anxiety disorders is not known. METHOD: Data from the Vietnam Era Twin Registry (n=7869, male twins) were examined in bivariate models to estimate genetic and shared and unique environmental contributions to PG and generalized anxiety disorder (GAD) and PG and panic disorder (PD). RESULTS: While both genetic and unique environmental factors contributed individually to PG, GAD, and PD, the best fitting model indicated that the relationship between PG and GAD was attributable predominantly to shared genetic contributions (r(A)=0.53). In contrast, substantial correlations were observed between both the genetic (r(A)=0.34) and unique environmental (r(E)=0.31) contributions to PG and PD. LIMITATIONS: Results may be limited to middle aged males. CONCLUSIONS: The existence of shared genetic contributions between PG and both GAD and PD suggests that specific genes, perhaps those involved in affect regulation or stress responsiveness, contribute to PG and anxiety disorders. Overlapping environmental contributions to the co-occurrence of PG and PD suggest that common life experiences (e.g., early life trauma) contribute to both PG and PD. Conversely, the data suggest that distinct environmental factors contribute to PG and GAD (e.g., early onset of gambling in PG). Future studies should examine the relationship between PG and anxiety disorders amongst other populations (women and adolescents) to identify specific genetic and environmental influences that account for the manifestation of these disorders and their co-occurrences.

Genetic architecture of learning and delayed recall: a twin study of episodic memory.

OBJECTIVE: Although episodic memory is often conceptualized as consisting of multiple component processes, there is a lack of understanding as to whether these processes are influenced by the same or different genetic determinants. The aim of the present study was to utilize multivariate twin analyses to elucidate the degree to which learning and delayed recall, two critical measures of episodic memory performance, have common or different genetic and environmental influences. METHOD: Participants from the Vietnam Era Twin Study of Aging (314 monozygotic twin pairs, 259 dizygotic twin pairs, and 47 unpaired twins) were assessed using the second edition of the California Verbal Learning Test. Mean age at the time of the evaluation was 55.4 years (SD = 2.5). RESULTS: Model fitting revealed the presence of a higher-order latent factor influencing learning, short- and long-delay free recall, with a heritability of .36. The best-fitting model also indicated specific genetic influences on learning, which accounted for 10% of the overall variance. Given that learning involves the acquisition and retrieval of information, whereas delayed recall involves only retrieval, we conclude that these specific effects are likely to reflect genes that are specific to acquisition processes. CONCLUSION: These results demonstrate that even in nonclinical populations, it is possible to differentiate component processes in episodic memory. These different genetic influences may have implications for gene association studies, as well as other genetic studies of cognitive aging and disorders of episodic memory such as Alzheimer's disease or mild cognitive impairment.

A twin study of spatial and non-spatial delayed response performance in middle age.

Delayed alternation and object alternation are classic spatial and non-spatial delayed response tasks. We tested 632 middle-aged male veteran twins on variants of these tasks in order to compare test difficulty, measure their inter-correlation, test order effects, and estimate heritabilities (proportion of observed variance due to genetic influences). Non-spatial alternation (NSA), which may involve greater reliance on processing of subgoals, was significantly more difficult than spatial alternation (SA). Despite their similarities, NSA and SA scores were uncorrelated. NSA performance was worse when administered second; there was no SA order effect. NSA scores were modestly heritable (h(2)=.25; 26); SA was not. There was shared genetic variance between NSA scores and general intellectual ability (r(g)=.55; .67), but this also suggests genetic influences specific to NSA. Compared with findings from small, selected control samples, high "failure" rates in this community-based sample raise concerns about interpretation of brain dysfunction in elderly or patient samples.

Risk of non-melanoma skin cancer in a national cohort of veterans with rheumatoid arthritis.

OBJECTIVE: To determine the incidence of and risk factors for non-melanoma skin cancer (NMSC) in a national cohort of veterans with RA. METHODS: We examined skin cancer risk in a cohort of 20 648 patients with RA derived from the Department of Veterans' Affairs (VA) national administrative databases. The cohort was divided into two medication groups: patients treated with non-biologic and TNF-α antagonist DMARDs. We defined skin cancer as the first occurrence of an International Classification of Disease, Version 9, Clinical Modification (ICD-9-CM) code for NMSC after initiation of a DMARD. Outcome risk was described using hazard ratios (HRs) with Cox proportional hazards regression for time-to-event analysis and logistic regression. We performed medical record review to validate the diagnosis of NMSC. RESULTS: Incidence of NMSC was 18.9 and 12.7 per 1000 patient-years in patients on TNF-α antagonists and non-biologic DMARDs, respectively. Patients on TNF-α antagonists had a higher risk of developing NMSC (HR 1.42; 95% CI 1.24, 1.63). Risk factors for NMSC included older age, male gender, NSAID and glucocorticoid use and a history of prior malignancies. There was substantial agreement between ICD-9-CM diagnosis of NMSC and medical record validation (κ = 0.61). CONCLUSION: TNF-α antagonist therapy in veterans with RA may be associated with an increased risk of NMSC, compared with therapy with non-biologic DMARDs. Rheumatologists should carefully screen patients receiving TNF-α antagonists for pre-cancerous skin lesions and skin cancer.

TNF-α antagonist use and risk of hospitalization for infection in a national cohort of veterans with rheumatoid arthritis.

Medications used to treat rheumatoid arthritis (RA) may confer an increased risk of infection. We conducted a retrospective cohort study of veterans with RA followed in the United States Department of Veterans Affairs health care system from October 1998 through September 2005. Risk of hospitalization for infection associated with tumor necrosis factor (TNF)-α antagonists therapy was measured using an extension of Cox proportional hazards regression, adjusting for demographic characteristics, comorbid illnesses, and other medications used to treat RA. A total of 20,814 patients met inclusion criteria, including 3796 patients who received infliximab, etanercept, or adalimumab. Among the study cohort, 1465 patients (7.0%) were hospitalized at least once for infection. There were 1889 hospitalizations for infection. The most common hospitalized infections were pneumonia, bronchitis, and cellulitis. Age and several comorbid medical conditions were associated with hospitalization for infection. Prednisone (hazard ratio [HR], 2.14; 95% confidence interval [CI], 1.88-2.43) and TNF-α antagonist use (HR, 1.24; 95% CI, 1.02-1.50) were associated with hospitalization for infection, while the use of disease-modifying antirheumatic drugs (DMARDs) other than TNF-α antagonists was not. Compared to etanercept, infliximab was associated with risk for hospitalization for infection (HR, 1.51; 95% CI, 1.14-2.00), while adalimumab use was not (HR, 0.95; 95% CI, 0.68-1.33). In all treatment groups, rate of hospitalization for infection was highest in the first 8 months of therapy. We conclude that patients with RA who are treated with TNF-α antagonists are at higher risk for hospitalization for infection than those treated with other DMARDs. Prednisone use is also a risk factor for hospitalization for infection.

Evidence of overlapping genetic diathesis of panic attacks and gastrointestinal disorders in a sample of male twin pairs.

We explored the comorbidity between panic attacks (PA), whose symptoms can include gastrointestinal discomfort, and gastrointestinal disorders (GD). Structural equation modeling was used to analyze data from 1,874 MZ and 1,498 DZ male-male twin pairs from the Vietnam Era Twin Registry. PA and GD were associated (relative risk for GD = 2). The percentage of liability due to genetic factors was estimated to be 37% for PA and 31% for GD. There was significant correlation between the genetic risk factors for PA and GD (estimated r = .55, 95% CI of 34% to 82%) and no evidence of correlation between the environmental causes of PA and GD. Therefore, PA and GD comorbidity can be explained by overlapping genetic factors and not overlapping environmental factors. Although these data cannot identify a biological pathway for such a shared liability, it suggests the presence of GD may be informative for genetic studies of panic.

Marriage and Divorce: A genetic perspective.

Marriage is considered one of the most important sources of social support that an individual receives as an adult. Although hypotheses have been formulated as to why individuals may dissolve a marriage, the determinants of marital success or failure are still relatively unknown. Behavioral geneticists have found that both marriage and divorce are, in part, genetically influenced. The goal of this research was to determine the degree of shared genetic and environmental variance between the two marital statuses. Participants were 6,225 twin pairs from the Vietnam Era Twin Registry. Data were obtained on marital history, and if the individual was no longer married, how the marriage ended. Univariate analyses were performed to determine the extent of genetic and environmental influences each of the marital statues (i.e., marriage and divorce), followed by a novel bivariate analysis to test the shared variance between marriage and divorce. Results from this analysis revealed that the two different marital statuses were influenced by entirely distinct genetic and environmental factors.

Psychopathic personality traits in middle-aged male twins: a behavior genetic investigation.

Psychopathic personality is characterized by interpersonal dominance, impulsivity, sensation seeking, poor planning, and aggressiveness. Studies have shown that the Multidimensional Personality Questionnaire (MPQ) can be used to estimate scores on the fearless-dominant (FD) and the impulsive-antisocial (IA) dimensions of the Psychopathic Personality Inventory (PPI), the best validated self-report measure of psychopathic personality traits. Prior behavior genetic studies reported roughly equal genetic and nonshared environmental influences for both FD and IA, which remained stable from adolescence to young adulthood. However, no prior studies address genetic and environmental influences on these dimensions beyond early adulthood. We utilized the classic twin method to examine genetic and environmental influences on variance in FD and IA in a sample of middle-aged male twins. Biometric modeling indicated that the variance in both factors is best explained by additive genetic and nonshared environmental influences. FD showed roughly equal contributions from genetic and environmental factors, whereas IA showed greater contributions from environmental than genetic factors. Additionally, the small phenotypic correlation between FD and IA was explained entirely by nonshared environmental factors.