Biomedical subjects

John K Hewitt

Publications and source records attributed to John K Hewitt.

6 recordsLinked to original sources

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

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

Review of twin and adoption studies of adolescent substance use.

OBJECTIVE: To review studies of adolescent substance use and abuse with genetically informative designs. METHOD: Twin and adoption studies of adolescent substance use were searched in Medline using keywords. RESULTS: Of 19 studies that used adolescent samples, 18 examined initiation or use of substances and 1 examined abuse. Of the 7 retrospective studies using adult samples, 6 examined problematic behaviors such as substance dependence. Genetic and shared environmental influences on adolescent substance use are moderated by the specific substance, age, gender, specific contexts, religiousness, and region. There is some evidence for a common genetic influence on substance use across substances. Genetic influences on adolescent substance use may act through an influence on disinhibited behavior. Shared environment contributed to adolescent substance use consistently across all adolescent samples and common shared environmental influences influenced initiation into tobacco and alcohol use. While parental alcohol use had a small influence on adolescent shared environment, sibling influences were substantial. CONCLUSIONS: Twin and adoption studies have increased our understanding of genetic and environmental influences on adolescent substance use and its initiation; however, more studies focusing on clinical syndromes of abuse and dependence are needed.

Adolescent↗

PubMed2003

Family transmission of marijuana use, abuse, and dependence.

OBJECTIVE: To examine the familial aggregation of marijuana use, abuse, and dependence. METHOD: Adolescents recruited from residential and day treatment programs for youths with conduct and substance problems, matched controls, and all available family members were interviewed with structured research instruments. A total of 2,546 individuals from 781 families were interviewed. Risk ratios of relatives of clinical cases were calculated, compared with controls, for marijuana use, abuse, or dependence. Spousal, parent-offspring, and sibling correlations and the proportion of variance attributable to parent-offspring transmission were estimated using structural equation modeling. RESULTS: For all three measures, the risk ratios were elevated in the family members of clinical probands, with estimates ranging from 1.5 to 3.3. Spousal correlations ranged from 0.33 to 0.70. Parent-offspring correlations ranged from 0.17 to 0.30. Sibling correlations ranged from 0.34 to 0.44. The proportion of variance attributable to factors transmitted from parents to children ranged between 25% and 44%. CONCLUSIONS: Familial aggregation of marijuana use, abuse, and dependence is present for all three measures. The results suggest significant parent-offspring transmission of risk, sibling environmental influences, and assortative mating for all three levels of marijuana use.

Adolescent↗

PubMed2003

The validity of analyses testing the etiology of comorbidity between two disorders: a review of family studies.

BACKGROUND: Knowledge regarding the causes of comorbidity between two disorders has a significant impact on research regarding the classification, treatment, and etiology of the disorders. Two main analytic methods have been used to test alternative explanations for the causes of comorbidity in family studies: biometric model fitting and family prevalence analyses. Unfortunately, the conclusions of family studies using these two methods have been conflicting. In the present study, we examined the validity of family prevalence analyses in testing alternative comorbidity models. METHOD: We reviewed 42 family studies that used family prevalence analyses to test three comorbidity models: the alternate forms model, the correlated liabilities model, or the three independent disorders model. We conducted the analyses used in these studies on datasets simulated under the assumptions of 13 alternative comorbidity models including the three models tested most often in the literature. RESULTS: Results suggest that some analyses may be valid tests of the alternate forms model (i.e., two disorders are alternate manifestations of a single liability), but that none of the analyses are valid tests of the correlated liabilities model (i.e., a significant correlation between the risk factors for the two disorders) or the three independent disorders model (i.e., the comorbid disorder is a third, independent disorder). CONCLUSION: Family studies using family prevalence analyses may have made incorrect conclusions regarding the etiology of comorbidity between disorders.

Adolescent↗

PubMed2002

Dopamine transporter polymorphism associated with externalizing behavior problems in children.

Early childhood externalizing behavior is a stable and heritable pattern of aggressive and delinquent behavior that often leads to the development of serious psychiatric disorders such as conduct disorder and attention deficit hyperactivity disorder. We examined the relationship between parent reported externalizing behavior (assessed at ages 4, 7, and 9 years) and the VNTR polymorphism of the 3' untranslated region of SLC6A3 (DAT1) in a community sample of 790 children ascertained as part of our longitudinal twin and adoption studies. We applied the sibling-based methodology developed by Fulker et al. [1999: Am J Hum Genet 64:259-267] for estimating allelic association with quantitative traits, while controlling for population stratification. An extension of these methods allowed for the inclusion of monozygotic twins, dizygotic twins, siblings, and singletons. We have demonstrated that the 9-repeat variant of the DAT1 is a significant risk allele for externalizing behavior at ages 4 (P=0.001) and 7 years (P=0.02). Although the effect size was negligible at age 9 (P=0.92), a formal test of the developmental decrease in effect across the three ages was non-significant (P=0.70).

Adolescent↗