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John K Hewitt

Publications and source records attributed to John K Hewitt.

At least 37 records · Page 2Linked to original sources
PubMed2006

Examination of the causes of covariation between conduct disorder symptoms and vulnerability to drug dependence.

Conduct disorder (CD) symptoms and substance dependence commonly co-occur. Both phenotypes are highly heritable and a common genetic influence on the covariation has been suggested. The aim of this study was to determine the extent to which genes and environment contribute to the covariance between CD and drug dependence using twins from the Colorado Longitudinal Twin Sample and the Colorado Twin Registry. A total of 880 twin pairs (237 monozygotic [MZ] female, 195 MZ male, 116 dizygotic [DZ] female, 118 DZ male and 214 DZ opposite-sex) aged 13 to 18 (mean = 15.65) were included in the analysis. CD was assessed by lifetime Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994) symptom count and a polysubstance dependence vulnerability index was developed from responses to the Composite International Diagnostic Interview--Substance Abuse Module. A bivariate Cholesky Decomposition model was used to partition the cause of variation and covariation of the two phenotypes. No sex-limitation was observed in our data, and male and female parameter estimates were constrained to be equal. Both CD symptoms and dependence vulnerability were significantly heritable, and genes, shared environment and nonshared environment all contributed to the covariation between them. Genes contributed 35% of the phenotypic covariance, shared environment contributed 46%, and nonshared environmental influences contributed the remaining 19% to the phenotypic covariance. Therefore, there appears to be pleiotropic genetic influence on CD symptoms and dependence vulnerability.

Adolescent↗
PubMed2005

Monoamine oxidase A (MAOA) and antisocial behaviors in the presence of childhood and adolescent maltreatment.

There is a robust relationship between the experience of maltreatment in childhood and later antisocial behaviors amongst adolescents and adults. Animal and human studies suggest that variation in monoamine oxidase A (MAOA) genotype may moderate the effects of maltreatment. Self-reported conduct problems and criminal convictions amongst sibling-pairs from the National Longitudinal Study of Adolescent Health were tested for association with reports of maltreatment before and after the age of 12. MAOA promoter polymorphisms were tested for possible moderation effects. Maltreatment predicted conduct problems and criminal convictions. MAOA genotype did not have a significant moderating effect in any of the six analyses that were conducted. We did not replicate a previous report that MAOA polymorphisms moderated the relationship between maltreatment and conduct problems. There was, however, a non-significant trend in the predicted direction. Additional studies will be needed before firm conclusions can be drawn about this hypothesized genotype-environment interaction.

Adolescent↗
PubMed2005

A genome-wide search for quantitative trait Loci that influence antisocial drug dependence in adolescence.

BACKGROUND: Among adolescents, externalizing problem behavior and substance use disorders are often comorbid. Familial influences, including shared genetic risk factors, may account for part of this comorbidity. Previously we reported 2 chromosomal regions (3q24-3q25 and 9q34) likely to contain genes that influence substance dependence vulnerability (DV) in adolescence. OBJECTIVES: To identify quantitative trait loci (QTLs) that influence externalizing problem behavior in adolescence and to determine whether any identified QTL overlap chromosomal regions that influence DV. DESIGN: Regression-based QTL mapping procedures designed for selected sibling pair samples. SETTING: Patient probands were drawn from consecutive admissions to residential and outpatient (milieu-type) treatment facilities for substance abuse and delinquency operated by the University of Colorado; most of these patients were referred for treatment by juvenile justice or social service agencies. PATIENTS: A total of 249 proband-sibling pairs from 191 families were selected for the study. Patient probands were 13 to 19 years of age; siblings of the probands ranged in age from 12 to 25 years. MAIN OUTCOME MEASURES: A community-based sample of 4493 adolescents and young adults was used to define clinically significant, heritable, age- and sex-normed indexes of DV, conduct disorder symptoms (CDS), and a composite index of antisocial substance dependence (DV + CDS). Siblings and parents were genotyped for 374 microsatellite markers distributed across the 22 autosomes (mean intermarker distance, 9.2 centimorgans). RESULTS: For both DV and CDS, there was evidence of linkage to the same region on chromosome 9q34, as well as to 3q24-3q25 for DV, and a novel region on chromosome 17q12 for CDS. Our composite index (DV + CDS) yielded the strongest evidence for linkage (logarithm of odds = 2.65) to the chromosome 9q34 region. CONCLUSION: These results provide the first evidence of a potential molecular genetic basis for the comorbidity between DV and antisocial behavior.

Adolescent↗
PubMed2005

Contributions of genes and environments to stability and change in externalizing and internalizing problems during elementary and middle school.

We examined longitudinally collected behavioral reports by teachers on a unique twin sample at the ages of 7, 8, 9, 10, 11, and 12 years. As twin and adoption studies implicate the role of genetic influence on behavioral problems found to be stable in epidemiological samples, the current study employs a developmental behavior genetic model to examine the extent to which genetic and environmental contributions to problem behaviors are stable and/or change during development. In this sample of 410 monozygotic (MZ) and 354 dizygotic (DZ) twins, MZ twins were rated as more similar than DZ twins on average. In general, boys were more frequently rated as displaying externalizing behaviors than were girls across each of the six observations, while girls' internalizing problems were found not to be significantly different from boys'. For both sexes, stability in externalizing problem behaviors was due to a single common genetic factor whose effects acted pleiotropically at each age in the presence of unique environmental influences that were transmitted from age-to-age. Change was largely due to uncorrelated age-specific non-shared environmental and additive genetic effects. Contributions to stability for internalizing problems were due to age-to-age transmission of earlier expressed genetic effects. Change for girls and boys internalizing problems were largely due to environmental experiences unique to siblings along with uncorrelated age-specific genetic effects. These results further inform the notion that individual environments are important factors in the etiology of problem behaviors, but suggest that heritable contributions to phenotypic stability are largely the same across middle childhood and early adolescence. Clinical implications of these findings are discussed.

Age Factors↗
PubMed2005

Testing hypotheses regarding the causes of comorbidity: examining the underlying deficits of comorbid disorders.

The authors examined the validity of a method commonly used to test alternative hypotheses regarding the causes of comorbidity: the examination of underlying deficits of comorbid disorders. The authors simulated data in which the true causes of comorbidity were known, then compared the patterns of underlying deficits of the comorbid disorders found in the simulated data with the predicted results. The method of examining the underlying deficits of comorbid disorders could distinguish between several comorbidity models, including those that could not be distinguished well using other methods. The ability to distinguish the correct model decreased as the sample size and the correlation between the underlying deficits and the symptom scores decreased, suggesting that the issue of power should be considered carefully.

Adult↗
PubMed2005

Genetic and environmental influences on conduct disorder: symptom, domain and full-scale analyses.

BACKGROUND: We used variable threshold models which accounted for age and gender differences to investigate the genetic and environmental influences on DSM-IV conduct disorder (CD) at the level of symptoms, aggressive versus non-aggressive domains, and full-scale. METHOD: A community sample of 1100 twin pairs (age 11-18) was interviewed using the Diagnostic Interview Schedule for Children. RESULTS: Behavior genetic model fitting suggested that genetic and environmental influences on individual symptoms varied by symptom. The best-fitting models for aggressive and non-aggressive domains, and full-scale CD included additive genetic effects and unique environmental effects only (AE models). These effects could be constrained across age cohorts and sex. The results suggest that using models that incorporate age- and gender-appropriate thresholds specific to each subject we can account for prevalence differences between cohorts. Heritability estimates were .49, .55 and .53 for the aggressive domain, non-aggressive domain, and full-scales, respectively. These results are in contrast to previous research on antisocial behavior measured with the CBCL reporting higher heritability for aggressive versus non-aggressive domains. CONCLUSIONS: Results suggest that individual symptoms of CD may be differentially heritable. Additionally, CD assessed using DSM-IV criteria may show differing patterns of heritability compared with estimates obtained for other measures of antisocial behavior such as the CBCL.

Adolescent↗
PubMed2004

Genetic influences on quantity of alcohol consumed by adolescents and young adults.

OBJECTIVE: To examine genetic and environmental influences on drinking in a nationally representative study of genetically informative adolescents followed into young adulthood. METHOD: The average quantity of alcohol used per drinking episode during the past year was analyzed in 4432 youth assessed during adolescence (mean age of 16) and then 1 and 6 years later. The variance of quantity of alcohol consumed was decomposed into three components: additive genetic (a2), shared environmental (c2), non-shared environmental (e2). Four candidate genes were tested for association. RESULTS: Wave 1 a2-0.52e2-0.48, Wave 2 a2-0.28e2-0.72, Wave 3 a2-0.30e2-0.70. Genetic correlations between Waves 1 and 2 were 0.85, Waves 1 and 3 were 0.34. The DAT1 440 allele was associated at Wave 1 (p=0.007). DRD2 TaqI A1/A2 was associated at Wave 3 (p=0.007). DRD4 and 5HTT were not associated. The DAT1 and DRD2 polymorphisms accounted for 3.1% and 2.0% of the variation, respectively. CONCLUSION: Genetic influence on drinking behavior was common in adolescents longitudinally assessed 1 year apart, but was less correlated between these adolescents and their assessment as young adults at a subsequent time point. Polymorphisms in genes of the dopaminergic system appear to influence variation in drinking behavior.

Adolescent↗
PubMed2004

Factor structure and concurrent validity of the Drug Use Screening Inventory in a community adolescent sample.

A variety of screening instruments for adolescent alcohol and drug abuse have been designed to be used within a clinical setting. This study adapted one of these instruments, the Drug Use Screening Inventory (DUSI), to be used within behavioral genetic or other epidemiological research on nonclinical samples. A primary goal of this study was to obtain a factor structure and set of subscales that might predict experimental and regular use of alcohol and drugs in a community sample. A secondary goal was to define subscales in a way that facilitated our interpretation and understanding of pathways to substance use and abuse. We investigated the underlying factor structure of items from four of the DUSI domains using a principal components analysis of the responses from 1266 adolescents from the Colorado Adolescent Twin Study. The resulting set of six subscales shows adequate internal consistency and provides an easily interpretable research tool for investigating etiological relationships between substance use problems and other risk behaviors.

Adolescent↗
PubMed2004

The validity of the Neale and Kendler model-fitting approach in examining the etiology of comorbidity.

Given that knowledge regarding the etiology of comorbidity between disorders can have a significant impact on research regarding the classification, treatment, and etiology of the disorders, the ability to reject incorrect hypotheses regarding the causes of comorbidity is very important. A simulation study was conducted to assess the validity of the Neale and Kendler (1995) model-fitting approach in examining the etiology of comorbidity between two disorders. First, data were simulated under the assumptions of the 13 alternative comorbidity models described by Neale and Kendler. Second, model-fitting analyses testing the comorbidity models were conducted on the simulated datasets. Thirteen sets of data with varying model parameters were simulated to test Neale and Kendler's assertion that their model-fitting approach is appropriate across a range of potential prevalences and degrees of familiality. The validity of the model-fitting approach in examining unselected twin data and a combination of selected family data and unselected family data was explored. The model-fitting approach successfully discriminated several classes of comorbidity models, although discrimination between models within classes of related models was less accurate. Results suggest that the model-fitting approach can be a useful tool in examining the etiology of the comorbidity between disorders if the caveats of the present study's results are considered carefully. As predicted by Neale and Kendler, variations in the disorder prevalences and familial correlations did not affect the validity of their model-fitting approach, but affected the power to discriminate the correct model. As suggested by Neale and Kendler, the model-fitting approach can be applied to both unselected and selected data and to both twin and family data.

Comorbidity↗
PubMed2004

Genetic and environmental contributions to general cognitive ability through the first 16 years of life.

The genetic and environmental contributions to the development of general cognitive ability throughout the first 16 years of life were examined using sibling data from the Colorado Adoption Project. Correlations were analyzed along with structural equation models to characterize the genetic and environmental influences on longitudinal stability and instability. Intraclass correlations reflected both considerable genetic influence at each age and modest shared environmental influence within and across ages. Modeling results suggested that genetic factors mediated phenotypic stability throughout this entire period, whereas most age-to-age instability appeared to be due to nonshared environmental influences.

Adolescent↗
PubMed2004

Investigating the genetic and environmental structure of Cloninger's personality dimensions in adolescence.

In this study we examined the genetic and environmental structure of four dimensions from Cloninger's personality system: novelty-seeking (NS), harm-avoidance (HA), reward-dependence (RD), and persistence (PS). Although adult twin studies suggest that these personality dimensions are moderately heritable, this is the first twin study of Cloninger's personality dimensions in adolescence--a period marked by significant physiological and social changes. Study participants included 1851 adolescent twins between the ages of 11 and 18 years; 878 complete twin pairs and 95 singleton-responding twins. Subjects were participants in two community-based samples of twins residing in the state of Colorado. Results indicated that cross-sectional mean levels for NS, HA and RD tended to show modest increases across the adolescent years, while PS showed modest mean decreases. Consistent sex differences in means were found only for RD. Univariate biometrical twin models were used to decompose trait variance into genetic and environmental sources. Results indicated that for NS, HA and RD additive genetic influences and unique environmental effects were sufficient to explain the data. PS, however, could be explained by unique and common environmental effects only, with different patterns of common environmental effects for males and females. We found moderate heritability estimates for NS, HA and RD ranging from .28 to .36--with no evidence for sex-limitation in those influences.

Adolescent↗
PubMed2004

Genetic influences on vulnerability to, and protective factors for, adolescent drinking.

Using behavioral genetic analyses, we investigated and present a possible relationship between adolescent alcohol use and six domains of common problem behaviors in a community-based sample of 633 twin pairs who were under the legal drinking age of 21 (mean age = 15.0 years). The underlying etiology of the six problem behavioral domains, classified as conduct problems, hyperactivity, school problems, low self-esteem, neuroticism, and social withdrawal, was previously described (Siewert et al., 2003) as two heritable and genetically distinct dimensions of problem behavior. We took the two best-fitting models from that study (one that proposed a generalized behavior problem factor along with an internalizing behavior factor, and one that proposed an externalizing behavior factor along with an internalizing behavior factor) and extended the analyses in this study to include an index of alcohol use. Our results suggest that there is a strong genetic relationship between adolescent alcohol use and a broad spectrum of both externalizing and internalizing behavioral problems. The individual who seems to be at risk for either generalized or specifically externalizing behavioral problems is also at risk for adolescent alcohol use. However, the individual who exhibits internalizing problem behaviors appears to be protected from adolescent alcohol use. We propose that adolescent alcohol consumption needs to be understood in the context of these genetically influenced externalizing and internalizing propensities.

Adolescent↗
PubMed2003

A genome-wide search for quantitative trait loci influencing substance dependence vulnerability in adolescence.

This study describes results from a genome-wide search for quantitative trait loci (QTL) influencing substance dependence vulnerability in adolescence. We utilized regression-based multipoint (and single-point) QTL mapping procedures designed for selected sibpair samples. Selected sibling pairs included 250 proband-sibling pairs from 192 families. Clinical probands (13-19 years of age) were drawn from consecutive admissions to substance abuse treatment facilities in the Denver metropolitan area; siblings of probands ranged in age from 12 to 25 years. In addition to the selected sample, a community-based sample of 3676 adolescents and young adults were utilized to define a clinically-significant, heritable, age- and sex-normed index of substance dependence vulnerability-a priori and independent of our linkage results. Siblings and their parents were genotyped for 374 STR micro-satellite markers distributed across the 22 autosomes (average inter-marker distance=9.2 cM). Non-parametric single-point linkage results indicated 17 markers on 11 chromosomes with nominally significant tests of linkage; six markers with LOD scores greater than 1.0 and one marker (D3S1614) with a LOD score of 2.2. Multipoint mapping corroborated two locations and provided preliminary evidence for linkage to regions on chromosome 3q24-25 (near markers D3S1279 and D3S1614) and chromosome 9q34 (near markers D9S1826 and D9S1838).

Adolescent↗
PubMed2003

Genetic and environmental influences on substance initiation, use, and problem use in adolescents.

BACKGROUND: We conducted a sibling/twin/adoption study of substance initiation, use, and problem use, estimating the relative contribution of genetic and environmental influences on these phenotypes in adolescents. METHODS: The participants were 345 monozygotic twin pairs, 337 dizygotic twin pairs, 306 biological sibling pairs, and 74 adoptive sibling pairs assessed by the Colorado Center for the Genetics and Treatment of Antisocial Drug Dependence, Denver and Boulder. The initiation, use, and problem use of tobacco, alcohol, marijuana, and other illicit drugs were assessed. Tetrachoric correlations were computed for each group, and univariate model-fitting analyses were conducted. RESULTS: There were moderate to substantial genetic influences, with the exception of alcohol use and any drug use, and modest to moderate shared environmental influences on substance initiation, use, and problem use. For alcohol and any drug, heritability was higher and the magnitude of shared environmental influences was lower for problem use than for initiation or use. Environmental influences shared only by twin pairs had a significant effect on tobacco initiation, alcohol use, and any drug use. For tobacco use, tobacco problem use, and marijuana initiation, heritability was higher and the magnitude of shared environmental influences was lower in female than in male adolescents. There was no evidence for sex-specific genetic or shared environmental influences on any variable. CONCLUSIONS: The moderate to substantial heritabilities found for adolescents in the present study are comparable to those found in twin studies of adult substance use and substance use disorders. The finding that problem use is more heritable than initiation and use is also consistent with the results of adult twin studies. The significance of environmental influences shared only by twin pairs on tobacco initiation, alcohol use, and any drug use suggests the influences of peers, accessibility of substances, and sibling interaction.

Adolescent↗
PubMed2003

Investigating age differences in the genetic and environmental structure of the tridimensional personality questionnaire in later adulthood.

In this study we examined cross-sectional age differences in means, phenotypic covariance structure, and the underlying genetic and environmental structure of four personality constructs from Cloninger's personality system: Novelty Seeking (NS), Harm Avoidance (HA), Reward Dependence (RD), and Persistence (PS). Study participants were same-sex female twins between the ages of 50 and 96, drawn from the American Association of Retired Persons (AARP) twin sample. We examined age differences by comparing younger (age 50-65) and older (age 661) cohorts (based on a median split of the sample) and by estimating biometrical model parameters as linear and quadratic functions of continuous age. Results indicated modest, but significant, mean-level declines across this age range for NS, RD, and PS. HA showed no significant mean differences. We found moderate heritability estimates for all of the TPQ higher-order personality dimensions, ranging from 0.16 to 0.62. No significant age differences in the proportion of genetic and environmental influences on the TPQ dimensions were found. For HA, RD, and PS there were no significant age-related differences in total variance. However, for NS we observed a decline in total phenotypic variance across age cohorts.

Age Factors↗
PubMed2003

The validity of analyses testing the etiology of comorbidity between two disorders: comparisons of disorder prevalences in families.

Klein and Riso proposed several alternative models explaining the causes of comorbidity between two disorders (KR models). For each comorbidity model, they also presented a set of predictions for comparing the prevalence of disorder A-only, disorder B-only, and disorder AB (i.e., both disorders) among the relatives of probands with A-only, B-only, AB and controls (i.e., the KR predictions). Neale and Kendler provided the quantitative expectations for these prevalences (i.e., the NK models) and suggested biometric model fitting as an alternative way of testing comorbidity models. Neale and Kendler also suggested that the KR predictions have limited use because variations in the model parameters may lead to different predictions. We tested the KR predictions on two sets of data simulated under the assumptions of the KR/NK models. The results predicted by Klein and Riso and the results derived from the simulated datasets matched in most cases, but there were several notable discrepancies between the two sets of results. First, these discrepancies may be due to variations in the model parameters although the KR predictions are valid tests of the model for some model parameter sets. Second, several KR predictions may not be valid because they do not consider the necessary conditions for the diagnosis of A-only and B-only or alternative routes to comorbidity that are not hypothesized in their comorbidity model, including the fact that some comorbid cases will result by chance in all comorbidity models.

Comorbidity↗
PubMed2003

Relationships between personality and preferred substance and motivations for use among adolescent substance abusers.

This study examined the utility of Cloninger's tridimensional personality theory (1986, 1987a) in predicting preferred substance of abuse and self-reported motivations for use among a sample of 200 adolescent substance abusers and 200 matched community control adolescents. Two primary hypotheses were tested: (1) Cloninger's type II profile is more strongly associated with stimulant use, and his type I profile is more strongly associated with substances having sedative-hypnotic effects; and 2) type II individuals will report motivations for use that focus primarily on obtaining positive rewards, whereas type I individuals will report motivations primarily concerning negative reinforcement or the avoidance of problems and negative life experiences. Our results did not show strong associations between Cloninger's Harm Avoidance and Reward Dependence dimensions and preferred substance or motivations for use. However, in partial support of the hypotheses examined here, we did find that individuals low in novelty seeking (NS) tended to prefer alcohol and marijuana, whereas those high in NS endorsed a wider range of preferred substances. High NS was associated with significantly greater stimulant use and motivations focused on obtaining positive rewards, whereas low NS was associated with greater sedative use and motivations related to avoiding negative emotions or negative life experiences.

Adolescent↗