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National Human Exposure Assessment Survey: analysis of exposure pathways and routes for arsenic and lead in EPA Region 5.

The National Human Exposure Assessment Survey (NHEXAS) Phase I field study conducted in EPA Region 5 (Great Lakes Area) provides extensive exposure data on a representative sample of approximately 250 residents of the region. Associated environmental media and biomarker (blood, urine) concentration data were also obtained for the study participants to aid in understanding of the relationships of exposures to both contaminant pathways and doses. Besides fulfilling the primary NHEXAS objectives, the NHEXAS data provided an opportunity to explore secondary usages, such as examining pathway to route of exposure relationships. A generic type of structural equation model was used to define the anticipated relationships among the various data types for both arsenic (As) and lead (Pb). Since, by design, only a few participants provided data for all sample types, implementing this model required that some media concentrations (outdoor air and soil) be imputed for subjects with missing information by using measurements collected in the same geographic area and time period. The model, and associated pairwise correlations, generally revealed significant but weak associations among the concentrations, exposures, and doses; the strongest associations occurred for the various air measurements (indoor versus outdoor and personal). The generally weak associations were thought to be partly due to the absence of complete coverage of nonresidential environmental media and to nonsynchronization of relevant measurement times and integration periods of collection across the various sample types. In general, relationships between the NHEXAS questionnaire data and the various concentration, exposure, and body-burden measures were also weak. The model results and the modeling exercise suggest several ways for optimizing the design of future exposure assessment studies that are aimed at supporting structural modeling activities.

Air Pollution↗

Cigarette use by adolescents: attitude-behavior relationships.

Structural equation models were used to test the effectiveness of various theories in predicting cigarette smoking among adolescents. Maximum-likelihood estimation, as implemented in LISREL for Windows 8.12, was used to compare the theory of reasoned action (TRA), the theory of planned behavior, and a modified version of the theory of reasoned action incorporating past behavior. Respondents consisted of 225 high school students who were questioned in 1994 about their attitudes, subjective norms, perceived behavioral control, past behavior, intentions, and actual behavior relating to the use of cigarettes. Results indicated that the modification of the TRA incorporating past behavior provided a marginally better fit than the other models. For this group of high school students, attitudes toward smoking, past behavior in relation to smoking, and perceptions of what significant others think they should do were significant predictors of their intentions to smoke. Intentions, together with past behavior, predicted their actual behavior. The models used in the present research show that this behavior can be explained with reference to a small number of key variables which are useful for furthering our understanding of the structure of adolescent smoking.

Adolescent↗

The structure of genetic and environmental risk factors for anxiety disorders in men and women.

BACKGROUND: The anxiety disorders exhibit high levels of lifetime comorbidity with one another. Understanding the underlying causes of this comorbidity can provide insight into the etiology of the disorders and inform classification and treatment. OBJECTIVE: To explain anxiety disorder comorbidity by examining the structure of the underlying genetic and environmental risk factors. DESIGN: Lifetime diagnoses for 6 anxiety disorders (generalized anxiety disorder, panic disorder, agoraphobia, social phobia, animal phobia, and situational phobia) were obtained during personal interviews from a population-based twin registry. Multivariate structural equation modeling that allowed for sex differences was performed. SETTING: General community sample. PARTICIPANTS: More than 5000 members of male-male and female-female twin pairs from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders. MAIN OUTCOME MEASURES: Parameter estimates for best-fitting model. RESULTS: The full model, which contained 2 common genetic, shared environmental, and unique environmental factors plus disorder-specific factors, could be constrained to equality across male and female study participants. In the best-fitting model, the genetic influences on anxiety were best explained by 2 additive genetic factors common across the disorders. The first loaded most strongly in generalized anxiety disorder, panic disorder, and agoraphobia, whereas the second loaded primarily in the 2 specific phobias. Social phobia was intermediate in that it was influenced by both genetic factors. A small role for shared environmental influences was observed owing to a single common factor that accounted for less than 12% of the total variance for any disorder. Unique environmental influences could be explained by a single common factor plus disorder-specific effects. CONCLUSIONS: The underlying structure of the genetic and environmental risk factors for the anxiety disorders is similar between men and women. Genes predispose to 2 broad groups of disorders dichotomized as panic-generalized-agoraphobic anxiety vs the specific phobias. The remaining associations between the disorders are largely explained by a unique environmental factor shared across the disorders and, to a lesser extent, a common shared environmental factor.

Adult↗

Twenty-five strategies for improving the design, implementation and analysis of health services research related to alcohol and other drug abuse treatment.

While some aspects of addiction can be studied in laboratory or controlled settings, the study of long-term recovery management and the health services that support it requires going out into the community and dealing with populations and systems that are much more diverse and less under our control. This in turn raises many methodological challenges for the health service researchers studying alcohol and other drug abuse treatment. This paper identifies some of these challenges related to the design, measurement, implementation and effectiveness of health services research. It then recommends 25 strategies (and key primers) for addressing them: (1) identifying in advance all stakeholders and issues; (2) developing conceptual models of intervention and context; (3) identifying the population to whom the conclusions will be generalized; (4) matching the research design to the question; (5) conducting randomized experiments only when appropriate and necessary; (6) balancing methodological and treatment concerns; (7) prioritizing analysis plans and increasing design sensitivity, (8) combining qualitative and quantitative methods; (9) identifying the four basic types of measures needed; (10) identifying and using standardized measures; (11) carefully balancing measurement selection and modification; (12) developing and evaluating modified and new measures when necessary; (13) identifying and tracking major clinical subgroups; (14) measuring and analyzing the actual pattern of services received; (15) incorporating implementation checks into the design; (16) incorporating baseline measures into the intervention; (17) monitoring implementation and dosage as a form of quality assurance; (18) developing procedures early to facilitate tracking and follow-up of study participants; (19) using more appropriate representations of the actual experiment; (20) using appropriate and sensitive standard deviation terms; (21) partialing out variance due to design or known sources prior to estimating experimental effect sizes; (22) using dimensional, interval and ratio measures to increase sensitivity to change; (23) using path or structural equation models; (24) integrating qualitative and quantitative analysis into reporting; and (25) using quasi-experiments, economic or organizational studies to answer other likely policy questions. Most of these strategies have been tried and tested in this and other areas, but are not widely used. Improving the state of the art of health services research and bridging the gap between research and practice do not depend upon using the most advanced methods, but rather upon using the most appropriate methods.

Alcoholism↗

Disability, physical activity, and muscle strength in older women: the Women's Health and Aging Study.

OBJECTIVE: To study associations of motor disability, physical activity, and muscle strength in older women, in particular to investigate whether model of spiraling decrease is expressed in the data. DESIGN: Cross-sectional analysis using data from the baseline measurements of The Women's Health and Aging Study (WHAS). SETTING: Participants' homes. PARTICIPANTS: A total of 1,002 disabled women aged 65 years and older living in the community. OUTCOME MEASURES: Motor disability was measured by the number of self-reported difficulties in grasping, lifting 101b, walking across a small room, walking 1/4 mile, climbing 10 steps, and doing heavy housework. Level of physical activity was determined from response to a series of questions on the frequency and amount of common activities and physical exercise. Hand grip and knee extension forces were measured using portable hand-held dynamometers. RESULTS: Disability and physical activity were inversely associated, with inactivity being most common among the most disabled women. Those with poorer strength reported more difficulties in motor activities. Greater strength was found among the physically more active. In stratified analyses, the positive association of physical activity on knee extension strength was consistent across disability levels. Multiple regression analysis showed that both physical activity and muscle strength were significant predictors for severity of disability. Structural equation model (LISREL) showed that muscle strength had a mediating role between physical activity and disability; disability was associated with physical inactivity, which correlated with lower muscle strength, which was associated with greater degree of disability. CONCLUSION: Even though causality cannot be confirmed in this cross-sectional analysis, our findings suggested a spiraling model of decline in which muscle strength has a significant role.

Activities of Daily Living↗

Social cognition in schizophrenia: relationships with neurocognition and negative symptoms.

Despite the growing importance of social cognition in schizophrenia, fundamental issues concerning the nature of social cognition in schizophrenia remain unanswered. One issue concerns the strength of the relationships between social cognition and key features of the disorder such as neurocognitive deficits and negative symptoms. The current study employed structural equation modeling to examine three key questions regarding the nature of social cognition in schizophrenia: 1) Are social cognition and neurocognition in schizophrenia better modeled as one or two separate constructs? 2) Are social cognition and negative symptoms in schizophrenia better modeled as one or two separate constructs?, and 3) When social cognition, neurocognition, and negative symptoms are included in a single model, is social cognition more closely related to neurocognition or to negative symptoms? In this cross sectional study, one hundred outpatients with schizophrenia or schizoaffective disorder were administered measures of social cognition, neurocognition, and negative symptoms. A two-factor model that represented social cognition and neurocognition as separate constructs fit the data significantly better than a one-factor model, suggesting that social cognition and neurocognition are distinct, yet highly related, constructs. Likewise, a two-factor model that represented social cognition and negative symptoms as separate constructs fit the data significantly better than a one-factor model, suggesting that social cognition and negative symptoms are distinct constructs. A three-factor model revealed that the relationship between social cognition and neurocognition was stronger than the relationship between social cognition and negative symptoms. The current findings start to provide insights into the structure of social cognition, neurocognition, and negative symptoms in schizophrenia.

Adult↗

Parental substance use disorder, mediating variables and adolescent drug use: a non-recursive model.

AIMS: To develop and test a non-recursive model that examines the effects of parental psychoactive substance use disorder (PSUD) on the reciprocal relationships among stressful life events, family attachment, peer drug use and adolescent drug use. DESIGN: A 3-year prospective cohort study followed adolescents from three types of families defined by a parental diagnosis of a psychiatric disorder. SETTING: A large metropolitan area in the upper Midwestern United States. PARTICIPANTS: Seven hundred and seventy-seven 10-16-year-old adolescents from three groups of families: 214 who resided in families in which a parent was diagnosed with PSUD, 181 who resided in families in which a parent was diagnosed with an affective disorder (but no co-morbid PSUD), and 382 who resided in families in which both parents were free of any diagnosable disorder. MEASUREMENTS: Psychiatric disorder was defined by the Structured Clinical Interview for DSM-III-R (SCID). Two follow-up interviews of adolescent respondents were used to measure stressful life events via the Junior High Life Experiences Survey, family attachment via FACES-III and a child-parent strain index, peer drug use, and two self-reported drug use scales designed to measure past-year alcohol use and illicit drug use (e.g. marijuana, cocaine, inhalants). FINDINGS: Nested structural equation models with latent variables revealed that adolescents from PSUD families were at heightened risk of stressful life events, peer drug use, attenuated family attachments and drug use during the first follow-up period. In turn, peer drug use was strongly associated with drug use during the second follow-up period. However, drug use during the first follow-up also led to greater peer drug use and attenuated family attachment during the second follow-up period. The findings support a non-recursive model describing relations among adolescent drug use, peer drug use and family attachment. CONCLUSIONS: Parental psychoactive substance use disorder puts adolescents at significant risk of becoming embedded in a cycle of drug use, associations with drug using peers, and poor family relations.

Adolescent↗

Modeling impairment: using the disablement process as a framework to evaluate determinants of hip and knee flexion.

Elders often present to health care providers with multiple inter-related conditions that determine an individual's ability to function. The disablement process provides a generalized sociomedical framework for investigating the complex pathways from chronic disease to disability. At each stage of the main pathway, associations may exist among primary physical factors and modifying variables that ultimately have downstream effects on the progression toward disability. The purpose of the present analysis is to examine the inter-relationships between a cohesive set of variables primarily at the level of impairment that may affect hip and knee flexion range of motion (ROM). The San Antonio Longitudinal Study of Aging enrolled 833 community dwelling Mexican (MA) and European American (EA) elders aged 64-78 years between 1992 and 1996. Of these, 647 had complete data from both a home-based and performance-based battery of assessments for these analyses. Concerning impairments, hip ROM was measured using an inclinometer, and knee ROM using a goniometer. Pain location and intensity were assessed using the McGill Pain Questionnaire. Peripheral vascular disease was assessed using doppler brachial and ankle systolic blood pressures. Ankle and knee reflexes, and vibratory sensation were assessed by a standardized neurological examination. As to diseases, diabetes was assessed using a combination of blood glucose levels and self-report, and arthritis by self-report. Concerning modifying variables, height and weight were directly measured and used to calculate BMI. Activity level was assessed with the Minnesota Leisure Time Questionnaire. Analgesic use was assessed by direct observation of medications taken within the past two weeks. We used structural equation modeling to test associations between the variables that were specified a priori. These analyses demonstrate the central role of BMI as a determinant of hip and knee flexion ROM. For an increase in level of BMI, the coefficients [SEM] for changes in levels of hip and knee ROM were -0.38 [0.05] and -0.26 [0.05], respectively. A higher BMI resulted in lower hip and knee ROM. BMI was also directly associated with prevalent diabetes (0.10 [0.05]) and arthritis (0.17 [0.05]). However, after adjustment for BMI, diabetes and arthritis did not have direct independent associations with either hip or knee ROM. BMI was also indirectly associated with knee, but not hip, ROM through paths including lower-leg pain, pain intensity, and neurosensory impairments. Diabetes had an indirect association with hip, but not knee ROM, through a path including peripheral vascular disease. In conclusion, BMI is a primary direct determinant of hip and knee ROM. The paths by which diabetes and arthritis lead to physical disability may be mediated, in part, at the level of impairment by BMI's association with joint range of motion. Interventions designed to decrease the impact of diabetes and arthritis on disability should track changes in BMI and joint ROM to measure the paths that account for the intervention's success. The observed associations suggest that interventions targeted to decrease BMI itself may lead to improved function in part through improved joint ROM.

Aged↗

Path analysis in genetic epidemiology: a critique.

Path analysis, a form of general linear structural equation models, is used in studies of human genetics data to discern genetic, environmental, and cultural factors contributing to familial resemblance. It postulates a set of linear and additive parametric relationships between phenotypes and genetic and cultural variables and then essentially uses the assumption of multivariate normality to estimate and perform tests of hypothesis on parameters. Such an approach has been advocated for the analysis of genetic epidemiological data by D. C. Rao, N. Morton, C. R. Cloninger, L. J. Eaves, and W. E. Nance, among others. This paper reviews and evaluates the formulations, assumptions, methodological procedures, interpretations, and applications of path analysis. To give perspective, we begin with a discussion of path analysis as it occurs in the form of general linear causal models in several disciplines of the social sciences. Several specific path analysis models applied to lipoprotein concentrations, IQ, and twin data are then reviewed to keep the presentation self-contained. The bulk of the critical discussion that follows is directed toward the following four facets of path analysis: (1) coherence of model specification and applicability to data; (2) plausibility of modeling assumptions; (3) interpretability and utility of the model; and (4) validity of statistical and computational procedures. In the concluding section, a brief discussion of the problem of appropriate model selection is presented, followed by a number of suggestions of essentially model-free alternative methods of use in the treatment of complex structured data such as occurs in genetic epidemiology.

Asian↗

PRIME--PRocess modelling in ImpleMEntation research: selecting a theoretical basis for interventions to change clinical practice.

BACKGROUND: Biomedical research constantly produces new findings but these are not routinely translated into health care practice. One way to address this problem is to develop effective interventions to translate research findings into practice. Currently a range of empirical interventions are available and systematic reviews of these have demonstrated that there is no single best intervention. This evidence base is difficult to use in routine settings because it cannot identify which intervention is most likely to be effective (or cost effective) in a particular situation. We need to establish a scientific rationale for interventions. As clinical practice is a form of human behaviour, theories of human behaviour that have proved useful in other similar settings may provide a basis for developing a scientific rationale for the choice of interventions to translate research findings into clinical practice. The objectives of the study are: to amplify and populate scientifically validated theories of behaviour with evidence from the experience of health professionals; to use this as a basis for developing predictive questionnaires using replicable methods; to identify which elements of the questionnaire (i.e., which theoretical constructs) predict clinical practice and distinguish between evidence compliant and non-compliant practice; and on the basis of these results, to identify variables (based on theoretical constructs) that might be prime targets for behaviour change interventions. METHODS: We will develop postal questionnaires measuring two motivational, three action and one stage theory to explore five behaviours with 800 general medical and 600 general dental practitioners. We will collect data on performance for each of the behaviours. The relationships between predictor variables (theoretical constructs) and outcome measures (data on performance) in each survey will be assessed using multiple regression analysis and structural equation modelling. In the final phase of the project, the findings from all surveys will be analysed simultaneously adopting a random effects approach to investigate whether the relationships between predictor variables and outcome measures are modified by behaviour, professional group or geographical location.

Biomedical Research↗

Hostility and pain are related to inflammation in older adults.

Chronically elevated systemic inflammation has a dramatic impact on health for older individuals. As stress-related responses, both hostility and pain perception may contribute to inflammation which in turn may maintain negative emotion and pain over time. We used structural equation modeling to examine the degree to which trait hostility and pain were uniquely associated with C-reactive protein (CRP) and serum IL-6 levels over a 6-year span in a sample of older adults. The sample included 113 present or former caregivers of a spouse with dementia and 101 non-caregivers. After accounting for depression, health behaviours, and other risk factors, which were also assessed longitudinally, pain and, to a lesser extent, hostility were uniquely associated with plasma levels of CRP but not IL-6. When examined separately, the association between pain and CRP was significant only for caregivers, while the association between hostility and CRP was comparable for the two groups. These findings suggest that hostility may play a role in a cycle of inflammation among older adults, and that pain may be particularly problematic for those under chronic stress. Our results also shed light on inflammation as a mechanism underlying the effects of hostility on cardiovascular disease morbidity and mortality.

Age Factors↗

Heritability of recurrent tonsillitis.

OBJECTIVE: To estimate the relative contribution of genetic and environmental effects on the variance in the liability of recurrent tonsillitis. DESIGN: Retrospective questionnaire data from a population-based cohort. SETTING: Population-based data from Norway. PARTICIPANTS: A total of 9479 Norwegian twins born between January 1, 1967, and December 31, 1979, identified through the Medical Birth Registry of Norway. Main Outcome Measure Recurrent tonsillitis. RESULTS: The lifetime prevalence of recurrent tonsillitis was 11.7% (95% confidence interval, 11.0%-12.3%), with a significant predominance of female cases. The tetrachoric correlations for monozygotic twins were 0.71 for males and 0.60 for females. For dizygotic twins, the correlations were 0.12 for males, 0.14 for females, and 0.24 for dizygotic pairs of opposite sex. Structural equation modeling indicated that genetic effects explained 62% of the variation in the liability of recurrent tonsillitis. The remaining variance was attributed to individual environmental effects. There was no evidence of sex-specific genetic effects on the liability of recurrent tonsillitis. CONCLUSION: There is evidence for a substantial genetic predisposition for recurrent tonsillitis.

Adult↗

Prediction of resource use during acute pediatric illnesses.

BACKGROUND: Significant resources are used for acute illnesses in children. Identifying predictors of resource use can focus interventions to reduce this use. OBJECTIVE: To determine the relative effects of maternal, infant, social milieu, and demographic characteristics, the mother-child interaction, and perception of illness severity on the use of resources during acute illnesses in children. DESIGN: At the 2-week and 6-, 15-, and 24-month well-child care visits of a cohort of mother-infant dyads, the mother-well-child interaction was assessed by using the Biringen Emotional Availability Scales, and data were gathered regarding maternal depression and sense of competence, infant temperament, maternal social support, the home environment, and demographic characteristics. At each of the cohort's 1983 ill-child care visits during 30 months of follow-up, the mother-ill-child interaction was assessed by using the Emotional Availability Scales, and mothers and pediatricians independently assessed illness severity using the Acute Illness Observation Scales. Resources used during the illnesses-over-the-counter and prescription medications, tests, hospitalizations, follow-up visits, and the emergency department-were assessed. SETTING: A hospital primary care center and an urban and a suburban private practice. Patients Between February 1, 1995, and March 30, 1998, a consecutive sample of 380 dyads were asked to enroll at the 2-week well-child care visit; 316 (83.2%) consented, and complete data were available for analysis of 243 dyads. MAIN OUTCOME MEASURES: A path analytic framework using a structural equation model assessed the presence and strength of predictive relationships between demographic, maternal, infant, and social milieu data, the Biringen Emotional Availability Scales, and the Acute Illness Observation Scales and the main outcome measure, resource use. RESULTS: Three variables predicted greater mean resource use during each acute illness episode: a less optimal mother-child interaction (beta = -.53), lower scores for parenting sense of competence (beta = -.26), and greater perception of illness severity by mothers (beta =.33). By using the coefficient of determination (R2), these 3 predictors account for 55% of the reliable variance in resource use during acute illnesses. CONCLUSION: The quality of the mother-child interaction, maternal sense of competence, and maternal assessment of severity of the illness are major predictors of resource use during acute pediatric illnesses, and should be important foci of interventions to reduce resource use.

Acute Disease↗

The lifetime history of major depression in women. Reliability of diagnosis and heritability.

BACKGROUND: In epidemiologic samples, the assessment of lifetime history (LTH) of major depression (MD) is not highly reliable. In female twins, we previously found that LTH of MD, as assessed at a single personal interview, was moderately heritable (approximately 40%). In that analysis, errors of measurement could not be discriminated from true environmental effects. METHODS: In 1721 female twins from a population-based register, including both members of 742 pairs, LTH of MD, covering approximately the same time period, was obtained twice, once by self-administered questionnaire and once at personal interview. RESULTS: Reliability of LTH of MD was modest (kappa = +.34, tetrachoric r = +.56) and was predicted by the number of depressive symptoms, treatment seeking, number of episodes, and degree of impairment. Deriving an "index of caseness" from these predictors, the estimated heritability of LTH of MD was greater for more restrictive definitions. Incorporating error of measurement into a structural equation model including both occasions of measurement, the estimated heritability of the liability to LTH of MD increased substantially (approximately 70%). More than half of what was considered environmental effects when LTH of MD was analyzed on the basis of one assessment appeared, when two assessments were used, to reflect measurement error. CONCLUSIONS: Major depression, as assessed over the lifetime, may be a rather highly heritable disorder of moderate reliability rather than a moderately heritable disorder of high reliability.

Adult↗

Does participation in psychosocial treatment augment the benefit of clozapine? Department of Veterans Affairs Cooperative Study Group on Clozapine in Refractory Schizophrenia.

BACKGROUND: This study examines the role of participation in psychosocial treatment as a mediator of the clinical effectiveness of clozapine. METHODS: Subjects participated in a 12-month double-blind random-assignment trial comparing clozapine and haloperidol in patients hospitalized 30 to 364 days for refractory schizophrenia at 15 Department of Veterans Affairs medical centers. A broker-advocate case management intervention was used to facilitate participation in psychosocial treatments and to document such participation. RESULTS: Between those who continued receiving clozapine (n=122) or a conventional antipsychotic drug (n=169) for 12 months, those receiving clozapine were more likely to participate in psychosocial rehabilitation treatment. Although they were no more likely to receive clinical recommendations for such treatments, they were more likely to both verbally accept recommendations and to act on them. Structural equation modeling shows that participation in psychosocial treatment did not play a mediating role in clozapine's effect on outcomes at 6 months, but was associated with both reduced symptoms and improved quality of life at 12 months. CONCLUSIONS: Clozapine facilitates participation in psychosocial treatment, and such enhanced participation is associated with improved quality-of-life and symptom outcomes. Psychosocial rehabilitation should be offered concomitantly with clozapine.

Adult↗

Distinct contributions of conduct and oppositional defiant symptoms to adult antisocial behavior: evidence from an adoption study.

BACKGROUND: We conducted an exploratory multivariate analysis of juvenile behavior symptoms in an adoption data set. One goal was to see if a few DSM-interpretable symptom dimensions economically captured information within the data. A second goal was to study the relationships between any such dimensions, biological and environmental background, and eventual adult antisocial behavior. METHODS: The data originated from a retrospective adoption study. Probands with a biological background for parental antisocial personality or alcoholism were heavily oversampled. Symptoms were ascertained by proband and adoptive parent interview. We performed, by gender, orthogonal rotated principal component analyses of juvenile behavior disturbance symptoms (females, n = 87; males, n = 88). We used structural equation modeling to examine the relationships hypothesized above. RESULTS: For both genders, an oppositional defiant disorder (ODD) component and at least 1 conduct component emerged. Regardless of the conduct component scores, the ODD components were significant predictors of adult antisocial behavior. For males, the ODD component was predicted by an antisocial biological background, but not by scores on the Adverse Adoptive Environment Scale. The conduct components were predicted by adoptive environment alone. For females, biological background or biological-environmental interactions predicted each of the components. CONCLUSIONS: There has been little previous distinction between conduct disorder and ODD in studies of genetic and environmental influences on juvenile behavior. The study suggests that adolescent ODD symptoms may be a distinct antecedent of adult antisocial personality. In males, adolescent ODD symptoms may represent early expression of genetic sociopathic personality traits.

Adolescent↗

Shared genetic risk of major depression, alcohol dependence, and marijuana dependence: contribution of antisocial personality disorder in men.

BACKGROUND: Little is known about genetic factors that underlie the interrelationships among antisocial personality disorder (ASPD), major depression (MD), alcohol dependence (AD), and marijuana dependence (MJD). We examined the contribution of genetic effects associated with ASPD to the comorbidity of MD and substance use disorders. METHODS: The Vietnam Era Twin Registry is a general population registry of male veteran twins constructed from computerized Department of Defense files and other sources. A telephone diagnostic interview was administered to eligible twins from the Registry in 1992. Of 5150 twin pairs who served on active military duty during the Vietnam era, 3360 pairs (1868 monozygotic and 1492 dizygotic) in which both members completed the pertinent diagnostic interview sections were included. The main outcome measures were lifetime DSM-III-R ASPD, MD, AD, and MJD. RESULTS: Structural equation modeling was performed to estimate additive genetic, shared environmental, and nonshared environmental effects common and specific to each disorder. The heritability estimates for lifetime ASPD, MD, AD, and MJD were 69%, 40%, 56%, and 50%, respectively. Genetic effects on ASPD accounted for 38%, 50%, and 58% of the total genetic variance in risk for MD, AD, and MJD, respectively. After controlling for genetic effects on ASPD, the partial genetic correlations of MD with AD and with MJD were no longer statistically significant. Genetic effects specific to MD and AD and familial effects specific to MJD remained statistically significant. Nonshared environmental contributions to the comorbidity in these disorders were small. CONCLUSIONS: In this sample, the shared genetic risk between MD and both AD and MJD was largely explained by genetic effects on ASPD, which in turn was associated with increased risk of each of the other disorders.

Adult↗

Family transmission and heritability of externalizing disorders: a twin-family study.

BACKGROUND: Antisocial behavior and substance dependence disorders exact a heavy financial and human cost on society. A better understanding of the mechanisms of familial transmission for these "externalizing" disorders is necessary to better understand their etiology and to help develop intervention strategies. OBJECTIVES: To determine the extent to which the family transmission of externalizing disorders is due to a general vs a disorder-specific vulnerability and, owing to the genetically informative nature of our data, to estimate the heritable vs environmental nature of these transmission effects. DESIGN: We used structural equation modeling to simultaneously estimate the general and specific transmission effects of 4 externalizing disorders: conduct disorder, adult antisocial behavior, alcohol dependence, and drug dependence. SETTING: Participants were recruited from the community and were interviewed in a university laboratory. PARTICIPANTS: The sample consisted of 542 families participating in the Minnesota Twin Family Study. All families included 17-year-old twins and their biological mother and father. MAIN OUTCOME MEASURES: Symptom counts of conduct disorder, the adult criteria for antisocial personality disorder, alcohol dependence, and drug dependence. RESULTS: Transmission of a general vulnerability to all the externalizing disorders accounted for most familial resemblance. This general vulnerability was highly heritable (h2 = 0.80). Disorder-specific vulnerabilities were also detected for conduct disorder, alcohol dependence, and drug dependence. CONCLUSIONS: The mechanism underlying the familial transmission of externalizing disorders is primarily a highly heritable general vulnerability. This general vulnerability or common risk factor should be the focus of research regarding the etiology and treatment of externalizing disorders.

Adolescent↗