J. Arthur Woodward

A Genomewide Scan for Loci Involved in Attention-Deficit/Hyperactivity Disorder

Attention deficit/hyperactivity disorder (ADHD) is a common heritable disorder with a childhood onset. Molecular genetic studies of ADHD have previously focused on examining the roles of specific candidate genes, primarily those involved in dopaminergic pathways. We have performed the first systematic genomewide linkage scan for loci influencing ADHD in 126 affected sib pairs, using a approximately 10-cM grid of microsatellite markers. Allele-sharing linkage methods enabled us to exclude any loci with a lambda(s) of > or =3 from 96% of the genome and those with a lambda(s) of > or =2.5 from 91%, indicating that there is unlikely to be a major gene involved in ADHD susceptibility in our sample. Under a strict diagnostic scheme we could exclude all screened regions of the X chromosome for a locus-specific lambda(s) of >/=2 in brother-brother pairs, demonstrating that the excess of affected males with ADHD is probably not attributable to a major X-linked effect. Qualitative trait maximum LOD score analyses pointed to a number of chromosomal sites that may contain genetic risk factors of moderate effect. None exceeded genomewide significance thresholds, but LOD scores were >1.5 for regions on 5p12, 10q26, 12q23, and 16p13. Quantitative-trait analysis of ADHD symptom counts implicated a region on 12p13 (maximum LOD 2.6) that also yielded a LOD >1 when qualitative methods were used. A survey of regions containing 36 genes that have been proposed as candidates for ADHD indicated that 29 of these genes, including DRD4 and DAT1, could be excluded for a lambda(s) of 2. Only three of the candidates-DRD5, 5HTT, and CALCYON-coincided with sites of positive linkage identified by our screen. Two of the regions highlighted in the present study, 2q24 and 16p13, coincided with the top linkage peaks reported by a recent genome-scan study of autistic sib pairs.

Inequalities among lower bounds to reliability: With applications to test construction and factor analysis

A chain of lower-bound inequalities leading to the greatest lower bound to reliability is established for the internal consistency of a composite of unit-weighted components. The chain includes the maximum split-half coefficient, the lowest coefficient consistent with nonimaginary common factors, and the lowest coefficient consistent with nonimaginary common and unique factors. Optimization theory is utilized to determine the conditions that are requisite for the inequalities. Convergence proofs demonstrate that the coefficients can be attained. Rapid algorithms obtain estimates of the coefficients with sample data. The theory yields methods for splitting items into maximally similar sets and for exploratory factor analysis based on a theoretical solution to the communality problem.

An empirical study of maturing out: conditional factors.

Using data from the California Civil Addict Program, the study tested hypotheses about the possible conditional nature of the process of maturing out of heroin addiction. Hypotheses were tested in a five-way contingency table using the log-linear model. Results show that maturing out of addiction with increasing age is inhibited by high levels of involvement in crime and drug dealing.

RHD Maternal-Fetal Genotype Incompatibility Increases Schizophrenia Susceptibility

Fetal events and obstetric complications are associated with schizophrenia. Here we report the results of a family-based candidate-gene study that assesses the role of maternal-fetal genotype incompatibility at the RHD locus in schizophrenia. We adapted the case-parent-trio log-linear modeling approach to test for RHD maternal-fetal genotype incompatibility and to distinguish this effect from a high-risk allele at or near the RHD locus and from a direct maternal effect alone. Eighty-eight patient-parent trios, 72 patient-mother pairs, and 21 patient-father pairs were genotyped at the RHD locus. Of the 181 patients, 62% were male and 81% were second born or later. Only three patients were born after prophylaxis against maternal isoimmunization had become common practice. There was significant evidence for an RHD maternal-fetal genotype incompatibility, and the incompatibility parameter was estimated at 2.6. There was no evidence to support linkage/association with schizophrenia at or near the RHD locus nor any evidence to support the role of maternal genotype effect alone. Our results replicate previous findings that implicate the RHD locus in schizophrenia, and the candidate-gene design of this study allows the elimination of alternative explanations for the role of this locus in disease. Thus, the present study provides increasing evidence that the RHD locus increases schizophrenia risk through a maternal-fetal genotype incompatibility mechanism that increases risk of an adverse prenatal environment (e.g., Rh incompatibility) rather than through linkage/association with the disorder, linkage disequilibrium with an unknown nearby susceptibility locus, or a direct maternal effect alone. This is the first candidate-gene study to explicitly test for and provide evidence of a maternal-fetal genotype incompatibility mechanism in schizophrenia.

HLA-B Maternal-Fetal Genotype Matching Increases Risk of Schizophrenia

Schizophrenia and human leukocyte antigen (HLA) matching between couples or between mothers and offspring have independently been associated with prenatal/obstetric complications, including preeclampsia and low birth weight. Here, we report the results of a family-based candidate-gene study that brings together these two disparate lines of research by assessing maternal-fetal genotype matching at HLA-A, -B, and -DRB1 as a risk factor of schizophrenia. We used a conditional-likelihood modeling approach with a sample of 274 families that had at least one offspring with schizophrenia or a related spectrum disorder. A statistically significant HLA-B maternal-fetal genotype-matching effect on schizophrenia was demonstrated for female offspring (P=.01; parameter estimate 1.7 [95% confidence interval 1.22-2.49]). Because the matching effect could be associated with pregnancy complications rather than with schizophrenia per se, these findings are consistent with the neurodevelopmental hypothesis of schizophrenia and with accumulating evidence that the prenatal period is involved in the origins of this disease. Our approach demonstrates how genetic markers can be used to characterize the biology of prenatal risk factors of schizophrenia.

A Head Start Reevaluation Positive Effects Are Not Yet Demonstrable

The Head Start data analyzed by Magidson (1977) were reanalyzed using Joreskogs (1976) LISREL methodology. Plausible statistical models were developed jor the data. The hypothesis that the Head Start program produced zero effects on the cognitive abilities of its participants was evaluated by several X 2 tests. In all cases, the null hypothe sis could not be rejected.

THE EFFECTS OF EFFORT ON STROOP INTERFERENCE

Abstract Stroop interference was defined as the difference in time needed to name the ink colors of printed color and color-related words versus control plus signs. The effect of effort on Stroop interference was studied using an inter-subject competition procedure designed to manipulate effort. In experiment 1, subjects in the competition group were successful at inhibiting Stroop interference when compared to the performance of subjects in the no-competition group. This result is consistent with theories that postulate attentional effects on Stroop interference. In experiment 2, the significant decrease in Stroop interference was accompanied by a significant reduction in recognition memory for Stroop list items. Therefore, Stroop interference was reduced at a stage during the processing of word meaning. This result is consistent with theories that locate Stroop interference before response output.

Construct validity of heroin abuse estimators

The construct validity of two methodologically unrelated procedures for estimating the prevalence of heroin abuse was studied using a covariance structure model-fitting approach. A factor analytic estimation procedure and a log-linear-based capture-recapture method of estimation were simultaneously applied to 24 major metropolitan areas of the nation. A test of the construct validity of these procedures for estimating the prevalence of heroin abuse was carried out in the context of structural equation models where the results of the two methods were compared directly.

Performing History: The Effects of a Dramatic Art-Based History Program on Student Achievement and Enjoyment

Abstract This study examines the influence of a dramatic art-based history program for fifth-grade students on both their learning and enjoyment of history. The program, called “Performing History,” reflects theories of effective use of drama in the classroom as well as successful ways to teach history. The program presents historical information as part of a coherent story embedded in a musical drama that students rehearse and perform. Students who participated in the program in fifth grade were assessed on a test of history knowledge when they were in sixth grade and compared to a control group that had not had access to the program. The sixth graders also were asked to rate how much they enjoy history. Results indicate that students who participated in the program showed higher levels of history knowledge and enjoyment of history than those in the control group, controlling for prior scores on standardized achievement tests. The effect on knowledge was partially mediated by level of enjoyment of history, which also predicted later scholastic achievement in history. The study suggests that dramatic art-based instruction improves historical knowledge, and that success may be attributed in part to an increase in student enjoyment.

Estimating the size of subpopulations of heroin users: applications of log-linear models to capture/recapture sampling.

This article reviews two of the major methodologies applied to estimation of the number of heroin abusers: survey research methods and the capture/recapture technique. The main focus of the paper is to show the flexibility of the capture/recapture approach in handling not only the dependence of samples of heroin users but also the nonhomogeneity of sampling probabilities, allowing estimation in populations which are mixtures of qualitatively different heroin user types. Models with these features are illustrated using both simulated and real heroin abuse data.