Biomedical subjects

James J Hudziak

Publications and source records attributed to James J Hudziak.

At least 19 recordsLinked to original sources

PubMed2007

Attention problems and attention-deficit/hyperactivity disorder in discordant and concordant monozygotic twins: evidence of environmental mediators.

OBJECTIVE: To study familial and nonfamilial environmental influences on attention problems and attention-deficit/hyperactivity disorder (ADHD) in monozygotic twins discordant and concordant-high and low for these traits. METHOD: Ninety-five twin pairs from The Netherlands Twin Register were selected. Longitudinal survey data were collected at 1, 2, 3, 5, 7, 10, and 12 years from parents, twins, and teachers. Mothers participated in a structured clinical interview when twins were between 10 and 17 years of age. RESULTS: Affected twins from discordant pairs scored higher than unaffected cotwins on multiple measures of attention problems, ADHD, and other behavior problems according to mother, teacher, and self. Behavioral discordance was evident at age 2 and all subsequent measurements. Compared with unaffected cotwins, affected twins had lower birth weight and delayed physical growth and motor development. Differences between discordant and concordant groups were reported for maternal smoking, sleeping in different rooms, and living with only one parent. CONCLUSIONS: Significant markers of ADHD are found in infancy and include low birth weight and delayed motor development. As the knowledge of specific genetic and environmental influences on ADHD increases, future studies may focus on their complex interplay.

Adolescent↗

PubMed2006

Genetic and environmental contributions underlying stability in childhood obsessive-compulsive behavior.

BACKGROUND: Little is known about the stability of obsessive-compulsive (OC) behavior during childhood. The objective of this study is to determine the developmental stability of pediatric OC behavior and the genetic and environmental influences on stability in a large population-based twin sample. METHODS: Maternal and paternal ratings on the 8-item Obsessive Compulsive Scale of the Child Behavior Checklist (CBCL-OCS) on Dutch mono- and dizygotic twin pairs from 8083 families were collected at ages 7, 10, and 12 years. Using a longitudinal twin design, stability of OC behavior and genetic and environmental influences on stability were determined. Using cutoff criteria, persistent, resilient, and new onset cases were identified in this sample. RESULTS: OC behavior assessed by the CBCL-OCS showed a moderate stability with phenotypic correlations of around .50 for boys and for girls. Stability of OC behavior was influenced by genetic factors, by environmental factors shared by children growing up in the same family, and by non-shared environmental factors. Stability for OCS was lower when categorical data were analyzed than when quantitative definitions were used. CONCLUSIONS: OC behavior is moderately stable in childhood. Stability of OC behavior is influenced by genetic, shared, and non-shared environmental factors.

Child↗

PubMed2006

Longitudinal stability of the CBCL-juvenile bipolar disorder phenotype: A study in Dutch twins.

BACKGROUND: The Child Behavior Checklist-juvenile bipolar disorder phenotype (CBCL-JBD) is a quantitative phenotype that is based on parental ratings of the behavior of the child. The phenotype is predictive of DSM-IV characterizations of BD and has been shown to be sensitive and specific. Its genetic architecture differs from that for inattentive, aggressive, or anxious-depressed syndromes. The purpose of this study is to assess the developmental stability of the CBCL-JBD phenotype across ages 7, 10, and 12 years in a large population-based twin sample and to examine its genetic architecture. METHODS: Longitudinal data on Dutch mono- and dizygotic twin pairs (N = 8013 pairs) are analyzed to decompose the stability of the CBCL-JBD phenotype into genetic and environmental contributions. RESULTS: Heritability of the CBCL-JBD increases with age (from 63% to 75%), whereas the effects of shared environment decrease (from 20% to 8%). The stability of the CBCL-JBD phenotype is high, with correlations between .66 and .77 across ages 7, 10, and 12 years. Genetic factors account for the majority of the stability of this phenotype. There were no sex differences in genetic architecture. CONCLUSIONS: Roughly 80% of the stability in childhood CBCL-JBD is a result of additive genetic effects.

Age Factors↗

PubMed2006

Latent class analysis shows strong heritability of the child behavior checklist-juvenile bipolar phenotype.

BACKGROUND: The Child Behavior Checklist (CBCL) has been used to provide a quantitative description of childhood bipolar disorder (BPAD). Many have reported that children in the clinical range on the Attention Problems (AP), Aggressive Behavior (AGG), and Anxious-Depressed (A/D) syndromes simultaneously are more likely to meet the criteria for childhood BPAD. The purpose of this study was to determine if Latent Class Analysis (LCA) could identify heritable phenotypes representing the CBCL-Juvenile Bipolar (CBCL-JBD) profile and whether this phenotype demonstrates increased frequency of suicidal endorsement. METHODS: The CBCL data were received by survey of mothers of twins in two large twin samples, the Netherlands Twin Registry. The setting for the study was the general community twin sample. Participants included 6246 10-year-old Dutch twins from the Netherlands Twin Registry. The main outcome measure consisted of the LCA on the items comprising the AP, AGG, and A/D subscales and means from the suicidal items #18 and #91 within classes. RESULTS: A 7 class model fit best for girls and an 8 class fit best for boys. The most common class for boys or girls was one with no symptoms. The CBCL-JBD phenotype was the least common--about 4%-5% of the boys and girls. This class was the only one that had significant elevations on the suicidal items of the CBCL. Gender differences were present across latent classes with girls showing no aggression without the CBCL-JBD phenotype and rarely showing attention problems in isolation. Evidence of high heritability of these latent classes was found with odds ratios. CONCLUSIONS: In a general population sample, LCA identifies a CBCL-JBD phenotype latent class that is associated with high rates of suicidality, is highly heritable, and speaks to the comorbidity between attention problems, aggressive behavior, and anxious/depression in children.

Aggression↗

PubMed2006

Interactions between child and parent temperament and child behavior problems.

OBJECTIVE: Few studies of temperament have tested goodness-of-fit theories of child behavior problems. In this study, we test the hypothesis that interactions between child and parent temperament dimensions predict levels of child psychopathology after controlling for the effects of these dimensions individually. METHODS: Temperament and psychopathology were assessed in a total of 175 children (97 boys, 78 girls; mean age, 10.99 years; SD, 3.66 years) using composite scores from multiple informants of the Junior Temperament and Character Inventory and the Achenbach System of Empirically Based Assessment. Parent temperament was assessed using the adult version of the Temperament and Character Inventory. Statistical analyses included multiple regression procedures to assess the contribution of child-parent temperament interactions after controlling for demographic variables, other types of child psychopathology, and the individual Temperament and Character Inventory and Junior Temperament and Character Inventory dimensions. RESULTS: Interactions between child and parent temperament dimensions predicted higher levels of externalizing, internalizing, and attention problems over and above the effects of these dimensions alone. Among others, the combination of high child novelty seeking with high maternal novelty was associated with child attention problems, whereas the combination of high child harm avoidance and high father harm avoidance was associated with increased child internalizing problems. Many child temperament dimensions also exerted significant effects independently. CONCLUSIONS: The association between a child temperament trait and psychopathology can be dependent upon the temperament of parents. These data lend support to previous theories of the importance of goodness-of-fit.

Age Factors↗

PubMed2006

Exploring the boundary between temperament and generalized anxiety disorder: a receiver operating characteristic analysis.

Studies of individuals with an increased tendency to experience negative emotions such as fear, sadness, and anger have documented links between this temperamental trait and anxiety disorders. There exists debate, however, concerning the degree to which high levels of a temperamental trait are a necessary and/or sufficient component of a DSM diagnosis. In this study, receiver operating characteristic (ROC) analyses assessed the relations between levels of harm avoidance (HA) and generalized anxiety disorder (GAD) diagnoses in 334 children and their parents. Analyses revealed HA scores to be highly predictive of GAD diagnoses in children (AUC=.791, P<.001) and adults (AUC=.818, P<.001). However, there were many individuals with high HA scores who did not qualify for a GAD diagnosis. These findings suggest that while there are strong associations between HA and GAD, high levels of HA are neither necessary nor sufficient in the formation of clinically significant anxiety symptoms.

Adolescent↗

PubMed2006

Genetic and environmental influences on cross-gender behavior and relation to behavior problems: a study of Dutch twins at ages 7 and 10 years.

The aim of this study was to investigate the prevalence of cross-gender behavior during childhood, to estimate the influence of genotype and environment on variation in cross-gender behavior, and to explore the association of cross-gender behavior with maternal ratings of behavior problems as indexed by the Internalizing and Externalizing scales of the Child Behavior Checklist (CBCL). Cross-gender behavior was assessed by two items from the CBCL: "behaves like opposite sex" and "wishes to be of opposite sex." As part of an ongoing longitudinal study of the Netherlands Twin Registry, mothers were asked to complete the CBCL for their twins when they were 7 (n approximately 14,000 twins) and 10 years old (n approximately 8,500 twins). The prevalence of cross-gender behavior (as measured by maternal report of behaving like or wishing to be the opposite sex) was 3.2% and 5.2% for 7-year-old boys and girls, respectively, and decreased to 2.4% and 3.3% for 10-year-old boys and girls. Surprisingly, the prevalence rate of cross-gender behavior of girls with a male co-twin was lower than of girls with a female co-twin. At both ages, the similarity for cross-gender behavior was greater in monozygotic than in dizygotic twins pairs. Genetic structural equation modeling showed that 70% of the variance in the liability of cross-gender behavior could be explained by genetic factors, at both ages and for both sexes. Cross-gender behavior was associated with higher scores on Internalizing and Externalizing problems, both in boys and in girls.

Child↗

PubMed2006

The Obsessive Compulsive Scale of the Child Behavior Checklist predicts obsessive-compulsive disorder: a receiver operating characteristic curve analysis.

BACKGROUND: The purpose of this study was to determine a score on the Obsessive Compulsive Scale (OCS) from the Child Behavior Checklist (CBCL) to screen for obsessive compulsive disorder (OCD) in children and to rigorously test the specificity and sensitivity of a single cutpoint. METHODS: A receiver operating characteristic (ROC) curve analysis was applied to data from 61 patients with clinically determined OCD, 64 clinical controls and 73 general population controls to determine the best sum score on the CBCL-OCS to predict confirmed OCD in children. Using the ROC-determined cutoff, this score was applied to a national sample of CBCL data from 2460 singleton children ages 4-18 and to 20,016 children ages 7-18 from three large general population twin samples to determine the estimated prevalence in the general population. RESULTS: Using a CBCL-OCS score of 5 demonstrated an area under the curve (AUC) of .88 with high sensitivity (92%) and moderate specificity (67%) compared to clinical controls. Compared to the general population controls, the AUC was .96 with high sensitivity (92%) and specificity (89%). In the twin samples, the number of participants with CBCL-OCS scores above this cutpoint was 2.3-7.1%. CONCLUSIONS: These findings suggest that the OCS of the CBCL may provide a highly effective way to screen for childhood OCD, and that the prevalence of childhood OCD may have been underestimated, thus prompting the need for further research into screening children for this condition.

Adolescent↗

PubMed2006

Symptoms versus impairment: the case for respecting DSM-IV's Criterion D.

Diagnosing ADHD based primarily on symptom reports assumes that the number/frequency of symptoms is tied closely to the impairment imposed on an individual's functioning. That presumed linkage encourages diagnosis more by Diagnostic and Statistical Manual of Mental Disorders (4th ed.) style symptom lists than well-defined, psychometrically sound assessments of impairment. The current study correlated measures reflecting each construct in four separate, large-scale ADHD research samples. Average correlation between symptoms and impairment accounted for less than 10% of variance. Symptoms never predicted more than 25% of the variance in impairment. When an ADHD group was formed according to a measure of current symptoms, the sample size shrunk by 77% when a criterion-based measure of impairment was added. The partial unlinking of symptoms and impairment has implications for decisions about the diagnostic process, research criteria for participant inclusion, prevalence estimates, gender ratios, evaluation of treatment effects, service delivery, and many other issues.

Adolescent↗

PubMed2006

The genetic architecture of neuroticism in 3301 Dutch adolescent twins as a function of age and sex: a study from the Dutch twin register.

The objective of this study was to estimate the magnitude of genetic and environmental influences to variation in adolescent neuroticism as a function of age and sex. Neuroticism was assessed using the Amsterdamse Biografische Vragenlijst (ABV): a self-report personality instrument similar in content to the Eysenck Personality Questionnaire. Genetic modeling procedures, including age as modifier, were fitted to the total sample of 3301 Dutch adolescent twins aged 12 to 17 years (mean age 15.5). Significant influences of additive genetic factors (.59, 95% confidence intervals [CI] .54-.63) and unshared environmental factors (.41, 95% CI .37-.45) were found. Our data did not support a role of shared environment. Results showed that different genes may influence variation in neuroticism between girls and boys. No interaction was found between the variance components and age. Results generally support prior findings in adults and young children that neuroticism is influenced principally by additive genetic and unique environmental factors. The magnitude of the genetic component appears higher in the present sample of adolescents than in most studies of adults. The present study suggests that, in adolescence, different genes are expressed in boys and girls.

Adolescent↗

PubMed2006

Influences on achieving motor milestones: a twin-singleton study.

In order to determine if twinning impacted achievement of motor milestones the attainment of early motor milestones in twins was examined and compared to published data from singletons of the same age from the same culture and birth years. We examined the influence of twinning, sex, zygosity and birth cohort (1987-2001) on the motor development of twins aged 0 to 24 months. Data on the attainment of motor milestones (turn, sit, crawl, stand and walk) of twins were collected from maternal reports. All data were corrected for gestational age. Data from the twin sample were compared to normative data from singletons, which were available from Child Health Clinics (CHC). Analyses across twin data and the CHC singleton data revealed no differences between twins and singletons in achievement of motor milestones. Girls were able to sit without support slightly earlier than boys, otherwise there were no other sex differences. Birth-order analyses revealed minimal but significant differences in turning over from back to belly and for sitting without support between the first- and second-born. Dizygotic (DZ) twins were faster than monozygotic (MZ) twins in achieving the moment of sit, crawl, stand and walk. Twins born in earlier cohorts were faster in reaching the moment of crawl, sit and walk. It is concluded that there are no differences in time of reaching motor milestones between twins and singletons within the normal range. Sex has minimal to no effect on motor development in early childhood. DZ twins achieve motor milestones sooner than MZ twins. Attainment of gross motor milestones (crawl, stand and walk) is delayed in later birth cohorts.

Analysis of Variance↗

PubMed2006

The latent class structure of ADHD is stable across informants.

Previous studies have looked at the structure of attention-deficit/hyperactivity disorder (ADHD) using latent class analysis (LCA) of Child Behavior Checklist (CBCL) or Diagnostic and Statistical Manual of Mental Disorders (DSM) symptom structure. These studies have identified distinct classes of children with inattentive, hyperactive, or combined subtypes and have used these classes to refine genetic analyses. The objective of the current report is to determine if the latent class structure of ADHD subtypes is consistent across informant using the Conners' Rating Scales (CRS). LCA was applied to CRS forms from mother, father, and teacher reports of 1837, 1329 and 1048 latency aged Dutch twins, respectively. The optimal solution for boys was a 5-class solution for mothers, a 3-class solution for fathers, and a 4-class solution for teachers. For girls, a 4-class solution for mothers and a 3-class for fathers and teachers was optimal. Children placed into a class by one informant had markedly increased odds ratio of being placed into the same or similar class by the other informants. Results from LCA using Dutch twins with the CRS show stability across informants suggesting that more stable phenotypes may be accessible for genotyping using a multi-informant approach.

Adult↗

PubMed2005

Prevalence and genetic architecture of Child Behavior Checklist-juvenile bipolar disorder.

BACKGROUND: No consensus has been reached yet on how best to characterize children with juvenile bipolar disorder (JBD). Several groups have shown that children on the attention problems (AP), aggressive behavior (AGG), and anxious-depressed (AD) syndromes of the Child Behavior Checklist (CBCL) are likely to meet criteria for DSM-JBD. We aimed to use a large population-based twin sample to evaluate the prevalence and genetic architecture of the CBCL-JBD (deviant on AP, AGG, and AD) phenotype and compare these data to children who are deviant on just the CBCL-AP syndrome. METHODS: Structural equation modeling (SEM) was applied to CBCL data from 5418, 3562, and 1971 Dutch twin pairs at ages 7, 10, and 12 years. RESULTS: The CBCL-JBD phenotype occurs in approximately 1% of children at each age. Among the children who meet criteria for the CBCL-AP phenotype ( approximately 5%), between 13 and 20% also meet criteria for CBCL-JBD. The best SEM for CBCL-JBD includes additive genetic, shared and unique environmental factors. The best SEM for CBCL-AP includes dominant and additive genetic and unique environmental factors. CONCLUSIONS: These data suggest that CBCL-JBD is common, and even more common among children who have severe attention problems. CBCL-JBD shows familial aggregation due to both genetic and shared environmental factors.

Adolescent↗

PubMed2005

Bupropion XL in adults with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled study.

BACKGROUND: Data remain limited on treatment strategies for adults with attention-deficit/hyperactivity disorder (ADHD). This study evaluated the efficacy and safety of an extended-release, once-daily formulation of bupropion (XL) in the treatment of adults with ADHD. METHODS: This multisite, placebo-controlled, 8-week prospective trial evaluated 162 adult patients diagnosed with ADHD (combined and inattentive types). Subjects were treated with up to 450 mg/day of bupropion XL. The primary efficacy endpoint was the proportion of ADHD responders (defined as at least a 30% reduction in the investigator-rated ADHD Rating Scale score) at week 8 (last observation carried forward [LOCF]). RESULTS: Bupropion XL responders (53%) exceeded placebo responders (31%) (p =.004 at week 8) with a significantly greater proportion of bupropion XL responders as early as week 2 (p = .01). Treatment effect size calculated for the ADHD Rating Scale total score was .6. Bupropion XL appeared to provide sustained benefit throughout the day compared with placebo (morning p =.033, afternoon p =.004, evening p = .024). Bupropion XL was safe and well tolerated, with no serious or unexpected adverse events and a low rate of drug-related study discontinuation (5%). CONCLUSIONS: The results from this multisite study indicate that bupropion XL is an effective and well-tolerated nonstimulant treatment for adult ADHD.

Analysis of Variance↗

PubMed2005

Contributions of parental alcoholism, prenatal substance exposure, and genetic transmission to child ADHD risk: a female twin study.

BACKGROUND: Genetic influences have been shown to play a major role in determining the risk of attention-deficit hyperactivity disorder (ADHD). In addition, prenatal exposure to nicotine and/or alcohol has also been suggested to increase risk of the disorder. Little attention, however, has been directed to investigating the roles of genetic transmission and prenatal exposure simultaneously. METHOD: Diagnostic telephone interview data from parents of Missouri adolescent female twin pairs born during 1975-1985 were analyzed. Logistic regression models were fitted to interview data from a total of 1936 twin pairs (1091 MZ and 845 DZ pairs) to determine the relative contributions of parental smoking and drinking behavior (both during and outside of pregnancy) as risk factors for DSM-IV ADHD. Structural equation models were fitted to determine the extent of residual genetic and environmental influences on ADHD risk while controlling for effects of prenatal and parental predictors on risk. RESULTS: ADHD was more likely to be diagnosed in girls whose mothers or fathers were alcohol dependent, whose mothers reported heavy alcohol use during pregnancy, and in those with low birth weight. Controlling for other risk factors, risk was not significantly increased in those whose mothers smoked during pregnancy. After allowing for effects of prenatal and childhood predictors, 86% of the residual variance in ADHD risk was attributable to genetic effects and 14% to non-shared environmental influences. CONCLUSIONS: Prenatal and parental risk factors may not be important mediators of influences on risk with much of the association between these variables and ADHD appearing to be indirect.

Adolescent↗

PubMed2005

The genetic and environmental contributions to oppositional defiant behavior: a multi-informant twin study.

OBJECTIVE: To estimate the genetic and environmental contributions to oppositional defiant behavior (ODB) from mother, father, and teacher report using the Conners Revised Short Forms in a large twin sample. METHOD: ODB data were collected from 1,595 mothers, 1,114 fathers, and 793 teachers of 7-year-old twin pairs from the Netherlands Twin Registry in the 1990-1992 cohort with an 80% response rate. Models were fit for each informant to determine the genetic, environmental, gender, and informant influences on ODB. RESULTS: Genetic analyses of the ODB quantitative scale showed additive genetic (A) by mother (55%), by father (57%), and by teacher (21% girls, 38% boys) unique environmental (E) (mother, 22%; father, 29%; teacher, 48% girls, 39% boys) and shared environmental (C) (mother, 14%; father, 23%; teacher, 31% girls, 23% boys) influences. CONCLUSIONS: Additive genetic and unique environmental factors account for the majority of the influences on ODB for boys and girls by all informants.

Attention Deficit and Disruptive Behavior Disorder↗

PubMed2005

Family, twin, adoption, and molecular genetic studies of juvenile bipolar disorder.

Juvenile bipolar disorder (JBD) has been a subject of significant research and debate. Phenotypic differences between JBD and adult-onset bipolar disorder have led researchers to question whether or not similar neuropathologic mechanisms will be found. While much is known about the genetic and environmental contributions to the adult-onset phenotype, less is known about their contributions to JBD. Here, we review family, twin, adoption, and molecular genetic studies of JBD. Behavioral genetic data suggest both genetic and environmental contributions to JBD, while molecular genetic studies find linkage to age of onset of bipolar disorder to chromosomes 12p, 14q, and 15q. Additionally, changes associated with symptom age of onset have been recently reported in the brain-derived neurotrophic factor (BDNF) and glycogen synthase kinase 3-beta (GSK3-beta) genes. We contend that further progress in discovering the precise genetic and environmental contributions to JBD may depend on advances in phenotypic refinement, an increased appreciation of comorbid conditions, and more investigation of the longitudinal course of the disorder.

Adoption↗

PubMed2005

The CBCL predicts DSM bipolar disorder in children: a receiver operating characteristic curve analysis.

BACKGROUND: No clear consensus has been reached yet on how best to characterize children who suffer from pediatric bipolar disorder (PBD). The CBCL-PBD profile on the Child Behavior Checklist (CBCL) has been consistently reported showing deviant findings on the Attention Problems, Aggressive Behavior, and Anxious-Depressed subscales. AIM: To examine the sensitivity and specificity of the proposed CBCL-PBD profile for determining DSM diagnosis of PBD. METHODS: We applied receiver operating characteristic (ROC) curve analysis to data from 471 probands from two family studies of attention-deficit hyperactivity disorder and their 410 siblings. RESULTS: The CBCL-PBD score demonstrated an area under the curve (AUC) of 0.97 for probands and 0.82 for siblings for current diagnosis of PBD, suggesting that the CBCL-PBD provided a highly efficient way of identifying subjects with a current diagnosis of PBD in this sample. CONCLUSIONS: These findings suggest that the CBCL-PBD may provide a highly efficient way of screening for childhood bipolar disorder.

Adolescent↗