Jack Goldberg

Genetic influences on DSM‐III‐R drug abuse and dependence: A study of 3,372 twin pairs

Research and clinical experience indicate that drug use disorders tend to run in families. The objective of this study was to distinguish between the family environment and genetic factors as the source of this observed family resemblance. Data were collected by telephone interview from members of the Vietnam Era Twin Registry, comprising male twin pairs who served in the U.S. military between 1965 and 1975. There were 3,372 pairs in which both twins participated. Drug use disorder was defined as receiving a diagnosis of drug abuse or dependence according to DSM-III-R; 10.1% of the sample had abused or been dependent on at least one illicit drug. A significant difference between concordance rates for monozygotic (26.2%) vs. dizygotic (16.5%) twins indicated a genetic influence on drug use disorder. Biometrical modeling indicated that genetic factors (34% of the variance), the environment shared by twins (28% of the variance), and the nonshared environment (38% of the variance) had significant influences of similar magnitudes on the individuals risk of developing a drug use disorder. These results support the application of molecular genetic approaches to elucidate the genetic influence on drug use disorder, as well as the potential efficacy of environmental intervention to reduce risk.

Genetic and environmental influences on posttraumatic stress disorder, alcohol and drug dependence in twin pairs

We investigated whether and to what degree genetic and environmental contributions overlap among posttraumatic stress disorder (PTSD), alcohol dependence (AD) and drug dependence (DD). Subjects were 3304 monozygotic and dizygotic male-male twin pair members of the Vietnam Era Twin Registry who participated in 1992 telephone administration of the Diagnostic Interview Schedule Version 3 Revised (DIS-3R). Genetic model fitting was performed to estimate the magnitude of genetic and environmental contributions to the lifetime co-occurrence of DSM-III-R PTSD, AD and DD. The liability for PTSD was partially due to a 15.3% genetic contribution common to AD and DD and 20.0% genetic contribution specific to PTSD. Risk for AD was partially due to a 55.7% genetic contribution common to PTSD and DD. Genetic influences common to PTSD and AD accounted for 25.2% of the total risk for DD. Specific family environmental influence accounted for 33.9% of the total variance in risk for DD. Remaining variance for all three disorders was due to unique environmental factors both common and specific to each phenotype. These results suggest that PTSD, AD and DD each have etiologically distinct components and also have significant genetic and unique environmental contributions in common.

Dietary beta-carotene, vitamin C, and risk of prostate cancer: Results from the Western Electric Study

&NA; Dietary factors are likely candidates for important determinants of prostatic cancer risk. Among the most investigated nutritional factors have been antioxidants. We evaluated dietary beta‐carotene and vitamin C in relation to subsequent risk of prostate cancer in a prospective study of 1,899 middleaged men. We combined prostate cancer cases diagnosed in the first 24 years of follow‐up with incident cases identified from the Health Care Financing Administration hospitalization and outpatient files during an additional 6‐year follow‐up period. We obtained death certificates for all decedents. During the 30‐year follow‐up, prostate cancer developed in 132 men. There was no indication that consumption of beta‐carotene or vitamin C was related to increased or decreased risk of prostate cancer. Relative risks for highest vs lowest quartiles of betacarotene and vitamin C intake were 1.27 [95% confidence interval (CI) = 0.75‐2.14] and 1.03 (95% CI = 0.59‐1.60), respectively, after adjustment for age, number of cigarettes smoked per day, dietary cholesterol and saturated fat, alcohol consumption, total energy intake, and occupation. Associations between intake of these nutrients and risk of prostate cancer differed depending on whether the cancer was diagnosed during the first 19 years of follow‐up or the next 11 years of follow‐up. Overall survival over the 30 years of follow‐up was positively associated with intake of beta‐carotene and vitamin C.

Interrelationship of genetic and environmental influences on conduct disorder and alcohol and marijuana dependence symptoms.

Data from the Vietnam Era Twin (VET) Registry were analyzed to explore the degree to which the same genetic and environmental factors contribute to childhood conduct disorder symptoms and to alcohol and marijuana dependence symptoms. Data on conduct disorder and alcohol and marijuana dependence were obtained from administration of the Diagnostic Interview Schedule to 1,856 monozygotic and 1,479 dizygotic male-male twin pair members of the VET Registry. Multivariate genetic models were compared to determine the genetic and environmental influences common and or specific to all three phenotypes. A full model that allowed for common genetic and environmental influences to all three phenotypes gave a good fit to the data, but the best fitting reduced model did not allow for a genetic influence on conduct disorder symptoms. Under the best fitting reduced model, genes explained 44.7% of the variance in risk for alcohol dependence symptoms. The genetic liability for symptoms of marijuana dependence was due to a 36.3% specific contribution and a 7.6% contribution from genes common with alcohol dependence symptoms. Family environmental contributions common to all three phenotypes explained 46.7%, 11.9%, and 21.3% of variance in risk for symptoms of conduct disorder, alcohol dependence, and marijuana dependence, respectively. Common family environmental factors contribute to risk of conduct disorder symptoms and alcohol and marijuana dependence symptoms. Common genetic influences contribute to risk of symptoms of alcohol dependence and marijuana dependence. While our findings suggest genes do not contribute to co-morbid conduct disorder symptoms, comparisons with other twin studies suggest that the role of genes in risk for conduct disorder remains uncertain.

A twin study of generalized anxiety disorder symptoms, panic disorder symptoms and post-traumatic stress disorder in men

Generalized anxiety disorder (GAD), panic disorder (PD) and post-traumatic stress disorder (PTSD) often co-occur. We investigated whether and to what degree genetic and environmental contributions overlap among symptoms of GAD, symptoms of PD and PTSD. Subjects were 3327 monozygotic and dizygotic male-male twin pair members of the Vietnam Era Twin Registry who participated in a 1992 telephone administration of the Diagnostic Interview Schedule Version 3 Revised (DIS3R). Genetic model fitting was performed to estimate the magnitude of genetic and environmental contributions to the lifetime co-occurrence of GAD symptoms, PD symptoms and PTSD. The liability for GAD symptoms was due to a 37.9% additive genetic contribution common to PD symptoms and PTSD. Liability for PD symptoms was due to a 20.7% additive genetic contribution common to GAD symptoms and PTSD, and a 20.1% additive genetic influence specific to PD symptoms. Additive genetic influences common to symptoms of GAD and PD accounted for 21.3% of the genetic variance in PTSD. Additive genetic influences specific to PTSD accounted for 13.6% of the genetic variance in PTSD. Remaining variance for all three disorders was due to unique environmental factors both common and specific to each phenotype. These results suggest that these disorders each have etiologically distinct components and also have significant genetic and unique environmental contributions in common.

Evidence for genetic influences common and specific to symptoms of generalized anxiety and panic

BACKGROUND Generalized anxiety disorder (GAD) and panic disorder (PD) often co-occur and have been shown to be heritable. Researchers have debated the validity of the distinction between GAD and PD. To test for distinction between disorders, we estimated the genetic and environmental contributions which were specific and common to GAD and PD in a cohort of male-male twin pairs. METHODS Data were obtained from a telephone interview performed in 1992 utilizing the Diagnostic Interview Schedule Version 3-Revised. Interviews were administered to 6724 male-male monozygotic and dizygotic twin pair members of the Vietnam Era Twin Registry. We defined lifetime GAD by the report of six or more DSM-III-R symptoms and lifetime PD by the report of four or more DSM-III-R symptoms. RESULTS The lifetime co-occurrence of GAD and PD was best explained by a model which did not include family environmental influences. The variance in risk for GAD was due to a 37.9% influence from additive genetic factors with the remainder due to unique environmental influences. The variance in risk for PD was due to a 22.6% additive genetic contribution which was common with GAD and a 21.2% non-additive genetic contribution specific to PD with the remainder of variance in risk for PD due to unique environmental influences. LIMITATIONS Results may be limited to middle aged males. Model fitting with full diagnostic criteria was not possible due to low prevalences. CONCLUSIONS Our data suggest a distinction in liability for GAD versus PD. The common genetic influence to GAD and PD may partially account for the risk of the co-occurrence of these disorders in a lifetime.

The Vietnam Era Twin Registry

The Vietnam Era Twin (VET) Registry is composed of 7369 middle-aged male-male twin pairs both of whom served in the military during the time of the Vietnam conflict (1965-1975). The Registry is a United States Department of Veterans Affairs resource that was originally constructed from military records; the Registry has been in existence for more than 15 years. It is one of the largest national twin registries in the US and currently has subjects living in all 50 states. Initially formed to address questions about the long-term health effects of service in Vietnam the Registry has evolved into a resource for genetic epidemiologic studies of mental and physical health conditions. The management and administration of the VET Registry is described with particular attention given to the processes involved with database maintenance and study coordination. Several waves of mail and telephone surveys have collected a wealth of health-related information on Registry twins. More recent data collection efforts have focused on specific sets of twin pairs and conducted detailed clinical or laboratory testing. New Registry initiatives for the future include the construction of a web site and the development of a DNA repository.

A twin study of chronic fatigue.

Objective The etiology of chronic fatigue syndrome is unknown, but genetic influences may be important in its expression. Our objective was to assess the role of genetic and environmental factors in unexplained chronic fatigue. Methods A classic twin study was conducted using 146 female-female twin pairs, of whom at least one member reported ≥6 months of fatigue. After completing questionnaires on symptoms, zygosity, physical health, and a psychiatric interview, twins were classified using three increasingly stringent definitions: 1) chronic fatigue for ≥6 months, 2) chronic fatigue not explained by exclusionary medical conditions, and 3) idiopathic chronic fatigue not explained by medical or psychiatric exclusionary criteria of the chronic fatigue syndrome case definition. Concordance rates in monozygotic and dizygotic twins were calculated for each fatigue definition along with estimates of the relative magnitude of genetic and environmental influences on chronic fatigue. Results The concordance rate was higher in monozygotic than dizygotic twins for each definition of chronic fatigue. For idiopathic chronic fatigue, the concordance rates were 55% in monozygotic and 19% in dizygotic twins (p = .042). The estimated heritability in liability was 19% (95% confidence interval = 0–56) for chronic fatigue ≥6 months, 30% (95% confidence interval = 0–81) for chronic fatigue not explained by medical conditions, and 51% (95% confidence interval = 7–96) for idiopathic chronic fatigue. Conclusions These results provide evidence supporting the familial aggregation of fatigue and suggest that genes may play a role in the etiology of chronic fatigue syndrome.

The expanded racial and ethnic codes in the Medicare data files: their completeness of coverage and accuracy.

OBJECTIVES This paper evaluates the new race/ethnicity codes for Asian Americans, Hispanics, and Native Americans that have recently been added to the Medicare enrollment database. METHODS The race/ethnicity code revisions made by the Health Care Financing Administration are described and evaluated by (1) comparing the numbers of persons identified as Asian Americans, Hispanics, and Native Americans with corresponding population census projections and (2) determining whether Medicare enrollees born in Asian and Hispanic countries are assigned Asian and Hispanic codes. RESULTS Among persons 65 years of age and older, approximately 24% of Hispanics, 17% of Native Americans, and 56% of Asian Americans are identifiable by the new codes. From 18% to 29% of enrollees 65 years old or older born in Mexico, Puerto Rico, and Cuba are coded as Hispanic, and from 14% to 73% of enrollees born in nine Asian countries are classified as Asian American. Classification is not random but is related to timing of migration and to country of origin. CONCLUSIONS Researchers should resist the temptation to base analyses on the revised Health Care Financing Administration race/ethnicity codes, since coverage is incomplete and biased.

Reliability and validity of a combat exposure index for vietnam era verterans

The reliability and validity of a self-report measure of combat exposure are examined in a cohort of male-male twin pairs who served in the military during the Vietnam era. Test-retest reliability for a five-level ordinal index of combat exposure is assessed by use of 192 duplicate sets of responses. The chance-corrected proportion in agreement (as measured by the kappa coefficient) is 0.84. As a measure of criterion-related validity, the combat index is correlated with the award of combat-related military medals ascertained from the military records. The probability of receiving a Purple Heart, Bronze Star, Commendation Medal and Combat Infantry Badge is associated strongly with the combat exposure index. These results show that this simple index is a reliable and valid measure of combat exposure.