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Objective: We sought to examine the relative importance of genetic and environmental factors for the MOS SF-36; a widely used, valid, and reliable measure of health-related quality of life and to discuss incorporating genetic influences into health services research.Data Sources: Data are from a nationally distributed, nonclinical cohort of 2928 middle age, middle-class, male-male twin members of the Vietnam Era Twin Registry.Study Design: This was a secondary data analysis, classic twin heritability analysis.Data Collection: A telephone survey was used to collect information on alcohol-related problems and health services use, including the SF-36.Principal Findings: Variance component analyses indicated that additive genetic factors accounted for 17% to 33% of the variance for each of the 8 domains of the SF-36. Shared environment accounted for 0% to 12% of the variance for each domain, with the majority of variance for each domain accounted for by nonshared, or unique environment and error. Physical and mental health summary measures indicated that approximately one-third of the variance was accounted for by additive genetic factors and the remainder accounted for by nonshared environment and error. Clinical condition, history of alcohol dependence, had a small-but-significant influence for all domains. Including condition proved to be a better-fitting model. However, confidence intervals temper uniform statistical significance for genetic factors.Conclusions: This study assessed the heritability of the SF-36 in a nonclinical, community sample of middle age, middle-class all-male twins. The moderate genetic effects on SF-36 domain and summary measures are new findings and thus may affect interpretations of SF-36 as a measure of health-related quality of life. Ideally, trait-based measures should identify genetic sources of variation and thus help understand any bias of the true effects of SF-36. Still the majority of variance is accounted for by nonshared or unique environmental factors and error. By extension, increased understanding of the importance of genetic and environmental factors that influence either predictors or outcomes of interest will expand the level of scientific debate in health services research and improve predictability. [ABSTRACT FROM AUTHOR]

Objective: To test the hypothesis that individual differences in episodic memory and verbal fluency in cognitively normal middle-aged adults will predict progression to amnestic mild cognitive impairment (MCI) after 6 years., Method: The cohort analyzed included 842 male twins who were cognitively normal at baseline (mean 56 years) and completed measures of episodic memory and verbal fluency at baseline and again 6 years later (mean 62 years)., Results: Poor episodic memory predicted progression to both amnestic MCI (odds ratio [OR], 4.42; 95% confidence interval [CI], 2.44-10.60) and nonamnestic MCI (OR, 1.92; 95% CI, 1.32-3.44). Poor semantic verbal fluency also independently predicted progression to amnestic MCI (OR, 1.86; 95% CI, 1.12-3.52). In the full sample, a semantic-specific fluency latent variable at wave 1 (which controls for letter fluency) predicted change in episodic memory at wave 2 (β = 0.13), but not vice versa (β = 0.04). Associations between episodic memory and verbal fluency factors were primarily explained by genetic, rather than environmental, correlations., Conclusions: Among individuals who were cognitively normal at wave 1, episodic memory moderately to strongly predicted progression to MCI at average age 62, emphasizing the fact that there is still meaningful variability even among cognitively normal individuals. Episodic memory, which is typically a primary focus for Alzheimer disease (AD) risk, declined earlier and more quickly than fluency. However, semantic fluency at average age 56 predicted 6-year change in memory as well as progression to amnestic MCI even after accounting for baseline memory performance. These findings emphasize the utility of memory and fluency measures in early identification of AD risk., (© 2020 American Academy of Neurology.)

Background: Virtually all adult studies of APOE genotypes and cognition have included individuals over 60. In older adults, epsilon 4 carriers may manifest greater cognitive asymmetries than non-epsilon 4 carriers even in the absence of overall mean differences. General cognitive ability may also be affected by aging and APOE genotype, but most studies have inadequately addressed this potential confound. The goals of this study were to examine, in middle age, the relationship of APOE genotype with episodic memory and verbal-visuospatial episodic memory asymmetries, after accounting for prior general cognitive ability., Method: We compared epsilon 4+ and epsilon 4- individuals in 626 male twins in their 50s. We examined verbal and visuospatial episodic memory and verbal-visual asymmetry scores after adjusting for cognitive ability at age 20. Analyses corrected for correlations between twin pair members., Results: Compared with epsilon 4- individuals, epsilon 4 carriers performed significantly more poorly on verbal, but not visuospatial memory, manifested significantly greater cognitive asymmetry, and also had significantly more concerns about memory. At age 20, epsilon 4 carriers had higher general cognitive ability than epsilon 4- individuals, and current memory differences were enhanced after adjusting for age 20 cognitive ability., Conclusions: Small, but significant, APOE-epsilon 4-related memory deficits appear in the sixth decade of life in individuals who show no signs of preclinical dementia. The results partially support studies of older adults that suggest that increased cognitive asymmetries reflect risk for dementia and are associated with the APOE-epsilon 4 genotype. The results also highlight the potential problems of not having accurate data on prior cognitive ability.

This study examines the association of individual and familial risk factors with exposure to trauma and posttraumatic stress disorder (PTSD) in male twins (N = 6744) from the Vietnam Era Twin Registry. Independent reports of familial psychopathology from co-twins were used to avoid the potential biases of the family history method. Risk for exposure to traumatic events was increased by service in Southeast Asia, preexisting conduct disorder, preexisting substance dependence, and a family history of mood disorders whose effects appear to be partly genetic. Preexisting mood disorders in the individual were associated with decreased odds of traumatic exposure. Risk of developing PTSD following exposure was increased by an earlier age at first trauma, exposure to multiple traumas, paternal depression, less than high school education at entry into the military, service in Southeast Asia, and preexisting conduct disorder, panic disorder or generalized anxiety disorder, and major depression. Results suggest the association of familial psychopathology and PTSD may be mediated by increased risk of traumatic exposure and by preexisting psychopathology.

The Harvard Twin Study of Substance Abuse was carried out with the members of the Vietnam Era Twin (VET) Registry. The VET Registry comprises over 8000 male twins who served in the United States military between 1965 and 1975 and were subsequently interviewed regarding their use of licit and illicit substances, as well as various types of psychopathology. Our research has demonstrated significant influences by genetic, shared environmental, and unique environmental factors on the abuse of illicit substances. Multivariate analyses have indicated that the co-occurrence of abuse of various types of illicit drugs reflects a common vulnerability, influenced by both genetic and environmental factors, that cuts across all categories of illicit drugs. We have also demonstrated that some drugs have unique determinants, both genetic and environmental, that are not shared with other drugs. In part, the genetic influence on marijuana abuse is mediated by genetic influence on subjective effects in response to the drug. The determinants of transitions from one stage of drug use to another differ depending on which drug or which transition is examined. We determined significant genetic influences on several aspects of nicotine and alcohol use separately, as well as genetic influences shared by both substances. We found that the co-occurrence of illicit drug abuse and major depression is due to unique environmental influences. The phenotypic association between symptoms of conduct disorder and alcohol and marijuana dependence is due largely to shared environmental influences. Our results, thus far, indicate a complex pattern of genetic and environmental influences on substance use and abuse.

Objective: To determine the contributions of psychological trauma (exposure to combat during the Vietnam War), genetic factors, childhood experiences shared by twin siblings, and unmeasured experiences not shared by twin siblings to the reporting of current physical health problems a mean of 19 years after military service., Methods: In 1987, a national sample of 2224 monozygotic and 1818 dizygotic male veteran members of the Vietnam Era Twin Registry participated in a survey of health. Genetic modeling was performed on cross-sectional physical health and combat exposure data derived from Registry twins., Results: Combat experiences explained a small proportion (0.7-8.4%) of the variance in the report of hypertension, respiratory conditions, persistent skin conditions, gastrointestinal disorders, joint disorders, and hearing problems. Childhood experiences shared by siblings are not clearly related to any health problem studied. By contrast, genetic factors explain 31 to 54% and noncombat experiences not shared by siblings explain 45 to 66% of the variance in current physical health status., Conclusions: Greater than 90% of the variance in reported current physical health problems in Vietnam era veterans is attributable to inherited factors and unmeasured environmental experiences not shared by twin siblings. The traumatic experience of combat makes only a small contribution to the report of current physical health problems. These results do not preclude the possibility that combat influenced the prevalence of illness shortly after military service or that combat may influence the development of illness in the future.

This study examines the association of symptoms of lifetime antisocial personality disorder (ASP) with marijuana abuse/dependence in Vietnam-era veteran male monozygotic twin pairs. In 1992, 1,874 monozygotic twin pairs responded to a structured psychiatric interview that obtained data on lifetime history of drug use and ASP. Among randomly selected individuals from each twin pair, 8 of 10 ASP symptoms were significantly more prevalent in persons with a lifetime history of marijuana abuse/dependence compared with those who had never abused any drug (p < .001). Among 99 marijuana discordant twin pairs, however, only two ASP symptoms, "failure to conform to social norms" (odds ratio, 2.8; 95% confidence interval, 1.5 to 5.5) and "reckless regard of own or other's personal safety" (odds ratio, 2.4; 95% confidence interval, 1.0 to 5.4) were significantly increased in marijuana abusing/dependent twins compared with their non-abusing/nondependent twin brother. After adjustment for conduct disorder, alcohol abuse/dependence, and exposure to combat in Vietnam, only "failure to conform to social norms of lawful behavior" (odds ratio, 2.42; 95% confidence interval, 1.12 to 5.21) remained significantly increased in twins with marijuana abuse/dependence.

The clinical utility of the DSM-II-R-proposed diagnostic category self-defeating personality disorder (SDPD) was assessed through the presentation of prototypic case histories to American and British psychiatrists and clinical psychologists. The most frequent diagnoses assigned were SDPD and personality disorder not otherwise specified; no alternative diagnoses were consistently provided. More than one in two professionals reported treating patients with a condition similar to the SDPD cases, and approximately 65% of these patients were reported to be female. American and British nonpatients were also assessed through the administration of an SDPD self-report questionnaire. The results suggest that the reported high prevalence of SDPD in the practitioners' patients is not a result of the expression of a general personality trait, and the reported greater incidence of SDPD in women is not a reflection of a normal, culturally learned, female behavior pattern.

The search for indicators of vulnerability has been important in schizophrenia research, but, as in many areas, progress has been impeded due to the heterogeneity of schizophrenic disorders. How one conceptualizes the observed heterogeneity is dependent upon the particular genetic model to which one subscribes. In this article, we delineate several models that may account for the distributions of vulnerability indicators in groups of schizophrenic patients and their ill and well relatives. We present these models for heuristic purposes so that they may serve to guide the interpretation of data with respect to the issue of teasing apart familial and nonfamilial environmental components of putative vulnerability indicators. It is suggested that investigators will profit by: a) efforts to combine psychiatric genetic paradigms in order to maximize the yield of family study data, and b) thinking in terms of comparing the ability of different models to account for research findings.

The capacity of a mouse-adapted strain of canine distemper virus (CDV) to induce central nervous system (CNS) disease in weanling mice was investigated. Lethality of infection was found to be mouse-strain-dependent. In sensitive strains, an acute meningoencephalomyelitis developed. Brain tissue from acutely ill animals demonstrated numerous foci of viral antigen, and extracts yielded infectious virus. Mice of resistant strains, notably the SJL strain, survived the effects of acute infection, appeared well for several weeks, and then began to develop signs of subacute CNS disease. Preliminary histopathologic examination of brain and cord from acutely ill animals revealed prominent perivascular mononuclear cell infiltrates, mononuclear cell meningitis, and gliosis. These features were also found in the subacute disease, where, however, the lesions were less severe. Also, in the latter, virus antigen could not be demonstrated. The results indicate that CDV infection of mice may provide a promising model system for the study of virus-induced chronic CNS disease.