Genetics and developmental psychopathology: 1. Phenotypic assessment in the Virginia Twin Study of Adolescent Behavioral Development.

We introduce an overlapping cohort sequential longitudinal study of behavioral development and psychopathology in a representative sample of 1412 pairs of twins aged 8 through 16 years. Multiple phenotypic assessments involve a full psychiatric interview with each child and each parent, and supplementary parental, teacher, and child interview material and questionnaires. For the first wave of assessments, the numbers of reported DSM-III-R symptoms of Major Depressive Disorder (MDD), Separation Anxiety Disorder (SAD), Overanxious Disorder (OAD), Oppositional Defiant Disorder (ODD), Conduct Disorder (CD), and Attention Deficit Hyperactivity Disorder (ADHD), assessed through interviews, confirm patterns of age and sex trends found in other epidemiological samples, but underscore their dependence on whether the child or the parent is the informant. Correlations across domains for symptoms reported by the same informant are often as large as correlations across informants for the same domain of symptoms. Factor analyses of these symptom counts, taking account of informant view and unreliability of assessment, show the high degree of correlation between SAD and OAD, between MDD and OAD, and between CD and ODD. ADHD symptoms are relatively independent of the other domains, but show moderate correlations with CD, ODD, and MDD. Factorially derived dimensional questionnaire scales, based on child, parental, and teacher reports, show patterns of relationship to symptom counts consistent with both convergent and discriminant validity as indices of liability to clinical symptoms. Across informants, questionnaire scales provide as good a prediction of symptoms as do clinical interviews. Multitrait-multimethod confirmatory factor analysis reveals the patterns of relationship between symptoms of psychiatric disorder in children taking due account of informant and unique sources of variance. Gender differences are consistent within the correlated clusters of ODD/CD and MDD/SAD/OAD, although there are disorder-specific age trends. There are large informant-specific influences on the reporting of symptoms in clinical interviews. Dimensional questionnaire scales provide a useful source of additional information. In subsequent analyses of genetic and environmental etiology of childhood psychopathology we must expect that results may differ by informant and method of assessment. Multivariate and developmental analyses that explore the sources of these differences will shed new light on the relationship between genetic and environmentally influenced vulnerability and the manifestation of psychopathology in specific circumstances.

Genetics and developmental psychopathology: 2. The main effects of genes and environment on behavioral problems in the Virginia Twin Study of Adolescent Behavioral Development.

Little is known about the contribution of genetic and environmental factors to risk for juvenile psychopathology. The Virginia Twin Study of Adolescent Behavioral Development allows these contributions to be estimated. A population-based, unselected sample of 1412 Caucasian twin pairs aged 8-16 years was ascertained through Virginia schools. Assessment of the children involved semi-structured face-to-face interviews with both twins and both parents using the Child and Adolescent Psychiatric Assessment (CAPA). Self-report questionnaires were also completed by parents, children, and teachers. Measures assessed DSM-III-R symptoms of Attention Deficit Hyperactivity Disorder (ADHD). Conduct Disorder, Oppositional Defiant Disorder, Overanxious Disorder, Separation Anxiety, and Depressive Disorder. Factorially derived questionnaire scales were also extracted. Scores were normalized and standardized by age and sex. Maximum likelihood methods were used to estimate contributions of additive and nonadditive genetic effects, the shared and unique environment, and sibling imitation or contrast effects. Estimates were tested for heterogeneity over sexes. Generally, monozygotic (MZ) twins correlated more highly than dizygotic (DZ) twins, parental ratings more than child ratings, and questionnaire scales more highly than interviews. DZ correlations were very low for measures of ADHD and DZ variances were greater than MZ variances for these variables. Correlations sometimes differed between sexes but those for boy-girl pairs were usually similar to those for like-sex pairs. Most of the measures showed small to moderate additive genetic effects and moderate to large effects of the unique individual environment. Measures of ADHD and related constructs showed marked sibling contrast effects. Some measures of oppositional behavior and conduct disorder showed shared environmental effects. There were marked sex differences in the genetic contribution to separation anxiety, otherwise similar genetic effects appear to be expressed in boys and girls. Effects of rater biases on the genetic analysis are considered. The study supports a widespread influence of genetic factors on risk to adolescent psychopathology and suggests that the contribution of different types of social influence may vary consistently across domains of measurement.

A twin-family study of self-report symptoms of panic-phobia and somatization.

Self-report symptoms of anxiety are widely used in mental health and social science research as an index of current psychiatric state. Previous twin studies have suggested that genetic factors account for a significant proportion of the variance in these symptoms. To replicate and extend these findings, we examined self-report symptoms of panic-phobia and somatization in the "Virginia 30,000" twin-family sample. Model fitting applied to 80 unique relationships in the twin-family pedigree produced the following major results: (i) genetic effects were significant for both symptom factors, accounting for between 25 and 49% of the total variance, with the exception of symptoms of panic-phobia in females, where they accounted for 15-16% of the variance; (ii) familial environmental effects were absent for symptoms of somatization, while for symptoms of panic-phobia they accounted for a very small proportion of variance in males (< or = 1.2%) and a modest proportion in females (6-17%); (iii) spousal correlations were present for both factors, ranging from +0.05 to +0.20; (iv) genetic factors which influenced symptoms were generally the same in males and females, although their effect was greater in males; (v) heritability estimates were lower in the population-based than in the volunteer sample; and (vi) when test-retest reliability was included in the model, results suggest that genetic factors account for at least half of the stable variance for all symptom factors, except panic-phobia in females. Our results support the validity of previous twin studies of self-report symptoms of anxiety and suggest that genetic factors significantly influence these symptoms but familial-environmental factors play little or no etiologic role.

Sources of individual differences in depressive symptoms: analysis of two samples of twins and their families.

OBJECTIVE: Self-reported symptoms of depression are commonly used in mental health research to assess current psychiatric state, yet wide variation in these symptoms among individuals has been found in both clinical and epidemiologic populations. The authors sought to understand, from a genetic-epidemiologic perspective, the sources of individual differences in depressive symptoms. METHODS: Self-reported symptoms of depression were assessed in two samples of twins and their spouses, parents, siblings, and offspring: one sample contained volunteer twins recruited through the American Association of Retired Persons and their relatives (N = 19,203 individuals) and the other contained twins from a population-based twin registry in Virginia and their relatives (N = 11,242 individuals). Model fitting by an iterative, diagonal, weighted least squares method was applied to the 80 different family relationships in the extended twin-family design. RESULTS: Independent analyses of the two samples revealed that the level of depressive symptoms was modestly familial, and familial resemblance could be explained solely by genetic factors and spousal resemblance. The estimated heritability of depressive symptoms was between 30% and 37%. There was no evidence that the liability to depressive symptoms was environmentally transmitted from parents to offspring or was influenced by environmental factors shared either generally among siblings or specifically between twins. With correction for unreliability of measurement, genetic factors accounted for half of the stable variance in depressive symptoms. CONCLUSIONS: Depressive symptoms in adulthood partly reflect enduring characteristics of temperament that are substantially influenced by hereditary factors but little, or not at all, by shared environmental experiences in the family of origin.

Genetic and environmental influences on lifetime alcohol-related problems in a volunteer sample of older twins.

Few studies have employed genetically informative designs to study the causes of alcohol-related problems in nonclinical populations. We report patterns of alcohol abuse in a community-based U.S. volunteer sample of 3,049 female and 1,070 male twins aged 50 to 96. Significant gender and age effects were found for self-report measures of current and lifetime alcohol-related problems, with higher prevalence among males and lower frequency among older birth cohorts. Significant associations were found between severity of alcohol abuse (adapted from Feighner criteria) and age of drinking onset, parental history of alcohol problems and, among males, lower educational attainment. Model-fitting analyses based on data from 650 identical and 479 fraternal twin pairs indicate substantial family resemblance for a variety of definitions of lifetime alcohol abuse and alcohol problems. The median estimate of genetic variance across several definitions of alcohol problems was 38.5%, while that for shared environmental influence was 15.5%. Gender heterogeneity was not found for magnitude of genetic and environmental influences, but these comparisons were limited by low statistical power. Findings are discussed with reference to the literature on alcohol abuse among older adults and the genetic epidemiology of alcoholism.

A model system for analysis of family resemblance in extended kinships of twins.

The "Virginia 30,000" comprise 29,698 subjects from the extended kinships of 5670 twin pairs. Over 80 unique correlations between relatives can be derived from these kinships, comprised of monozygotic (MZ) and dizygotic (DZ) twins and their spouses, parents, siblings, and children. This paper describes the first application of a fairly general model for family resemblance to data from the Virginia 30,000. The model assesses the contributions of additive and dominant genetic effects in the presence of vertical cultural inheritance, phenotypic assortative mating, shared twin and sibling environments, and within-family environment. The genetic and environmental effects can be dependent on sex. Assortment and cultural inheritance may be based either on the phenotype as measured or on a latent trait of which the measured phenotype is an unreliable index. The model was applied to church attendance data from this study. The results show that the contributions of genes, vertical cultural inheritance, and genotype-environment covariance are all important, but their contributions are significantly heterogeneous over sexes. Phenotypic assortative mating has a major impact on family resemblance in church attendance.

Environmental and genetic influences on alcohol use in a volunteer sample of older twins.

A growing literature supports genetic contributions to familial resemblance for alcohol use characteristics, but few studies have focused on the mechanisms underlying alcohol use among older persons. We report patterns of alcohol use in a U.S. volunteer sample of 3,049 female and 1,070 male twins aged 50 to 96. Significant gender and age effects were found for self-report measures of current and lifetime alcohol use, with greater intake among males and current and lifetime abstinence more common among older participants. Comparisons with data obtained 4 years previously revealed high stability for quantity and frequency of alcohol consumption. Twin pairs with more frequent social contact tended to be more similar for lifetime and current alcohol use. Biometrical genetic modeling results indicate that use of alcohol is highly familial, with both genetic and shared environmental factors contributing to initiation of alcohol use among men and women. Among drinkers, however, the degree of twin resemblance for consumption behaviors is low to moderate and appears to be regulated by shared genes rather than shared environments. These data are consistent with a multidimensional process, suggesting that the determinants of whether one drinks in older age differ from those underlying how much or how often alcohol is consumed.

Religion and education as mediators of attitudes: a multivariate analysis.

The transmission of social attitudes has been investigated as a possible model of cultural inheritance in a sample of 3810 twin pairs from the Australian National Health and Medical Research Twin Registry. Six social attitude factors were identified and univariate genetic models fitted to scores on each factor. A joint multivariate genetic analysis of the six attitude factors, church attendance, and education indicated that the attitudes were correlated--the same genes and shared environments influenced more than one attitude factor. A current controversy regarding social attitudes is whether the significant loadings on this shared environmental component represent true cultural influences or are actually the genetic consequences of phenotypic assortative mating for church attendance and educational attainment (Martin et al., 1986). In our data, church attendance is almost entirely due to the impact of the shared environment. The large shared environmental component on church attendance also accounts for a substantial part of the family resemblance in social attitudes, suggesting that not all of the apparent cultural effects found in earlier studies can be ascribed to the genetic effects of assortative mating. However, church attendance and education do not completely account for the cultural component. Therefore, effects in addition to church attendance, education, and assortative mating for church attendance and education must be involved in the cultural component of the inheritance of attitudes.