Judy Silberg

Assortative mating for major psychiatric diagnoses in two population-based samples

BACKGROUND Previous studies on assortment for psychiatric disorders have reported discrepant findings. We aimed to test whether there is a significant association for psychiatric diagnoses, including alcoholism, generalized anxiety disorder, major depressive disorder, panic disorder and phobias between husbands and wives in two population-based samples. We further evaluated whether marital resemblance occurs primarily within or across psychiatric disorders and if assortment for psychopathology is primary or secondary to assortment for correlated variables. METHODS A model for mate selection addressed whether the correlation between mates for psychiatric disorders arises from direct assortment (primary homogamy) or through correlation with other variables for which assortment occurs (secondary homogamy) or through cross-variable assortment. The model accounted for within-person co-morbidity as well as across-spouse data. RESULTS Findings suggested that a moderate degree of assortment exists both within and across psychiatric diagnoses. Only a small amount of the observed marital resemblance for mental illness could be explained by assortment for correlated variables such as age, religious attendance and education. Similar results were obtained for the two samples separately and confirmed in their joint analysis, revealing that the co-morbidity and assortment findings, except for the marital correlation for age, religious attendance and education, replicate across samples. CONCLUSIONS Significant but moderate primary assortment exists for psychiatric disorders. The bias in twin studies that have ignored the small amount of assortment is negligible.

The analysis of parental ratings of children's behavior using LISREL.

A common procedure for assessing childrens behavior is to obtain parental ratings of the child. Since the ratings obtained are a function of both parent and child, disentangling the childs phenotype from that of the rater becomes an important methodological problem. For the analysis of genetic and environmental contributions to childrens behavior, solutions to this are available when multiple raters, e.g., two parents, rate multiple children, e.g., twins. This paper describes and illustrates simple LISREL models for the analysis of parental ratings of childrens behavior. We show how the assumption that mothers and fathers are rating the same behavior in children can be contrasted with the weaker alternative that parents are rating correlated behaviors. Given the stronger assumption, which appears adequate for ratings of childrens internalizing behavior problems, the contribution of rater bias and unreliability may be separated from the shared and nonshared environmental components of variation in a behavior genetic analysis.

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.

Analyzing twin resemblance in multisymptom data: Genetic applications of a latent class model for symptoms of conduct disorder in juvenile boys

A model based on the latent class model is developed for the effects of genes and environment on multivariate categorical data in twins. The model captures many essential features of dimensional and categorical conceptions of complex behavioral phenotypes and can include, as special cases, a variety of major locus models including those that allow for etiological heterogeneity, differential sensitivity of latent classes to measured covariates, and genotype × environment interaction (G×E). Many features of the model are illustrated by an application to ratings on eight items relating to conduct disorder selected from the Rutter Parent Questionnaire (RPQ). Mothers rated their 8-to 16-year-old male twin offspring [174 monozygotic (MZ) and 164 dizygotic (DZ) pairs]. The impact of age on the frequency of reported symptoms was relatively slight. Preliminary latent class analysis suggests that four classes are required to explain the reported behavioral profiles of the individual twins. A more detailed analysis of the pairwise response profiles reveals a significant association between twins for membership of latent classes and that the association is greater in MZ than DZ twins, suggesting that genetic factors played a significant role in class membership. Further analysis shows that the frequencies of MZ pairs discordant for membership of some latent classes are close to zero, while others are definitely not zero. One possible explanation of this finding is that the items reflect underlying etiological heterogeneity, with some response profiles reflecting genetic categories and others revealing a latent environmental risk factor. We explore two “four-class” models for etiological heterogeneity which make different assumptions about the way in which genes and environment interact to produce complex disease phenotypes. The first model allows for genetic heterogeneity that is expressed only in individuals exposed to a high-risk (“predisposing”) environment. The second model allows the environment to differentiate two forms of the disorder in individuals of high genetic risk. The first model fits better than the second, but neither fits as well as the general model for four latent classes associated in twins. The results suggest that a single-locus/two-allele model cannot fit the data on these eight items even when we allow for etiological heterogeneity. The pattern of endorsement probabilities associated with each of the four classes precludes a simple “unidimensional” model for the latent process underlying variation in symptom profile in this population. The extension of the approach to larger pedigrees and to linkage analysis is briefly considered.

Genetic and environmental influences on child reports of manifest anxiety and symptoms of separation anxiety and overanxious disorders: a community-based twin study.

Genetic and environmental influences in the determination of individual differences in self-reported symptoms of separation anxiety (SAD), overanxious disorder (OAD), and manifest anxiety (MANX) were evaluated in children and adolescents for three age groups (8–10, 11–13, and 14–16). Symptom counts for SAD and OAD were assessed for 1412 twin pairs using the childrens version of the Child and Adolescent Psychiatric Assessment, and MANX scores were based on child report from the Revised Childrens Manifest Anxiety Scales. Despite significant age and gender differences in thresholds of liability for child reports of symptoms of SAD and OAD, additive genetic and environmental effects could be set equal across age and gender for these variables. For MANX, however, the best-fitting model was a common effects sex-limitation model with estimates of heritabiliry varying dependent upon age and gender. Parameter estimates from the ACE models of OAD and SAD showed that additive genetic variation was a necessary component in the explanation of individual differences in child-reported symptoms of OAD (h2 = .37) across gender, but does not appear to be a major contributor to the explanation of individual differences in symptoms of SAD reported by children. Shared environmental effects (c2 = .40) were found to play a moderate role for SAD but could be dropped from the model for OAD and from all of the age groups for MANX, although the parameter approached significance among 11 yr to 13-year-old males.

Monoamine oxidase A and childhood adversity as risk factors for conduct disorder in females

BACKGROUND Recent studies among males have reported a genotype-environment interaction (GxE) in which low-activity alleles at the monoamine oxidase A (MAOA) locus conferred greater sensitivity to the effects of childhood adversity on risk for conduct disorder (CD). So far, few studies of females have controlled for gene-environment correlation or used females heterozygous for this X-linked gene. METHOD Logistic regression analysis of a sample of 721 females ages 8-17 years from the longitudinal Virginia Twin Study of Adolescent Behavioral Development (VTSABD) assessed the additive effects of MAOA genotypes on risk for CD, together with the main effect of childhood adversity and parental antisocial personality disorder (ASP), as well as the interaction of MAOA with childhood adversity on risk for CD. RESULTS A significant main effect of genotype on risk for CD was detected, where low-activity MAOA imparted the greatest risk to CD in girls while controlling for the significant effects of maternal ASP and childhood adversity. Significant GxE with weak effect was detected when environmental exposure was untransformed, indicating a higher sensitivity to childhood adversity in the presence of the high-activity MAOA allele. The interaction was no longer statistically significant after applying a ridit transformation to reflect the sample sizes exposed at each level of childhood adversity. CONCLUSIONS The main effect of MAOA on risk for CD in females, its absence in males and directional difference of interaction is suggestive of genotype-sex interaction. As the effect of GxE on risk for CD was weak, its inclusion is not justified.

Familial aggregation for conduct disorder symptomatology: the role of genes, marital discord and family adaptability.

BACKGROUND There is extensive evidence of statistical associations between family discord/ maladaptation and antisocial behaviour in the children, but questions remain on the extent to which the psychopathological risks are genetically or environmentally mediated. METHODS Twin pairs (N = 1,350), aged 8 to 16 years, in the general population-based Virginia Twin Study of Adolescent Behavioral Development were assessed using the Child and Adolescent Psychiatric Assessment interview administered separately to both twins and both parents. Structured interviews for parental lifetime psychiatric disorders were also administered to the mothers and fathers. Maternal reports on Olssons Family Adaptability and Cohesiveness questionnaire and the Dyadic Adjustment Scale were used as indices of the family environment. A path analytical model based on an extended twin-family design was used to test hypotheses about parent offspring similarity for conduct disorder symptomatology. RESULTS Family discord and maladaptation, which intercorrelated at 0.63, were associated with a roughly two-fold increase in risk for conduct disorder symptomatology. When parental conduct disorder was included in the model the environmental mediation effect for family maladaptation remained, but that for family discord was lost. CONCLUSION It is concluded that there is true environmental mediation from family maladaptation, operating as a shared effect, which accounts for 3.5 % of the phenotypic variance. The assumptions underlying this genetic research strategy are made explicit, together with its strengths and limitations.

The application of structural equation modeling to maternal ratings of twins' behavioral and emotional problems.

The application of structural equation modeling to twin data is used to assess the impact of genetic and environmental factors on childrens behavioral and emotional functioning. The models are applied to the maternal ratings of behavior of a subsample of 515 monozygotic and 749 dizygotic juvenile twin pairs, ages 8 through 16, obtained through mailed questionnaires as part of the Medical College of Virginia Adolescent Behavioral Development Twin Project. The importance of genetic, shared, and specific environmental factors for explaining variation is reported for both externalizing and internalizing behaviors, as well as significant differences in the causes of variation in externalizing behaviors among young boys and girls. The usefulness of applying structural equation models to data on monozygotic and dizygotic twins and the potential implications for addressing clinically relevant questions regarding the causes of psychopathology are discussed.

Multiple raters of disruptive child behavior: Using a genetic strategy to examine shared views and bias

Most research on child behavior incorporates information from different individuals. While agreement between informants is generally only modest, there is little understanding of the processes underlying disagreement. In twin studies, differential agreement among raters for MZ and DZ twins is of particular concern. The processes underlying differences among mother, father, and child ratings of oppositional and conduct disorder symptoms are explored. Evidence in favor of a shared parental view of behavior is presented. Parental ratings give higher intrapair correlations, which could be due to either parents rating their twins more similarly or twins contrasting themselves. Rater bias and situational specificity are among the possible explanations of differential ratings. The effects of incorporating multiple raters of behavior on estimates of genetic and environmental effects are explored. These suggest that genetic influences are greater for the shared (multiple-rater) phenotype than for individual ratings; reduction in measurement error is only a partial explanation.

An evaluation of different approaches for behavior genetic analyses with psychiatric symptom scores.

We used a simulation study to evaluate six approaches for behavior genetic analyses of psychiatric symptom scores. For the selection of the correct model, the best results were obtained with approaches using transformed scores in combination with a procedure involving p-values. With normalizing transformations, the χ2 test statistic gave a reasonable impression of the overall fit of the model but was less accurate when used as a difference test. The asymptotic distribution free estimation methods yielded χ2s that were much too large. All data analysis techniques yielded substantially biased parameter estimates. The most biased results were obtained with normalizing transformations. The least biased results were obtained with tobit correlations, but because of its large standard errors the most precise estimates were obtained with polychoric correlations and optimal scale scores. An empirical study showed that a recognition of the role of methodological factors was helpful to understand part of the differences between assessment instruments, raters, and data analysis techniques that were found in the real data.