Biomedical subjects

John K Hewitt

Publications and source records attributed to John K Hewitt.

42 records · Page 3Linked to original sources

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↗

PubMed2003

Sibling-based association analyses of the serotonin transporter polymorphism and internalizing behavior problems in children.

BACKGROUND: Childhood internalizing problems are often precursors in the development of more serious psychiatric syndromes including anxiety and depressive disorders. Twin studies of the etiology of these disorders suggest that the genetic risk factors underlying anxiety and depression are highly correlated. However, the specific genetic mechanisms responsible for this risk have not yet been identified. METHODS: We examined the association between childhood internalizing problems and a functional polymorphism in the serotonin transporter gene (5-HTTLPR) in 711 children participating in a longitudinal twin study of behavioral and emotional development. Internalizing problems were measured at ages 4, 7, 9, 10, 11 and 12 years using the Child Behavior Checklist (CBCL) parent report form. We applied a sibling-based methodology for estimating allelic association with quantitative traits, while controlling for population stratification. RESULTS: No associations were found for CBCL Internalizing problems at any age, including the subscales for Somatic Complaints, Withdrawn and Anxiety/Depression. CONCLUSIONS: Thus, although our results did not support the hypothesis that the 5-HTTLPR contributes to a dimensional expression of internalizing behavior problems, this does not rule out the possibility that it is an interesting polymorphism to pursue in the search for genetic risk factors related to major depressive and/or anxiety disorders.

Anxiety Disorders↗

PubMed2003

Genetic and environmental analysis of behavioral risk factors for adolescent drug use in a community twin sample.

We investigated the etiology of six problem behaviors that might facilitate an understanding of behavioral pathways to substance use and abuse in adolescents. These behavioral measures, classified as Conduct Problems, Hyperactivity, School Problems, Low Self-esteem, Neuroticism, and Social Withdrawal were the result of a previously reported (Siewert et al., 2003) modification of the Drug Use Screening Inventory (DUSI; Tarter, 1990; Tarter & Hegedus, 1991). We developed these measures as interpretable components of risk for substance use and abuse in a community based sample of 633 twin pairs, who were under the legal drinking age of 21 (mean age = 15.0 years). Using multivariate analyses, model comparisons indicated that these six behavioral measures could be thought of as two heritable, and genetically distinct, dimensions of problem behavior. Two closely competing models resulted from our analyses. The best fitting model hypothesized a general genetic factor loading on all 6 behavioral measures with a second genetic factor loading on only the three internalizing behavioral measures with loadings of 0.25-0.59 and 0.26-0.44, respectively. A second model, which fit the data almost as well, hypothesized one genetic factor loading only on the externalizing behavioral measures, and a second genetic factor loading only on the internalizing behavioral measures, with a correlation between the two latent factors of 0.75. Because our analyses show that there are two genetically distinct factors influencing these six problem behaviors, we anticipate that there may be different patterns of relationship of these factors to risk for substance use, abuse, and dependence.

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↗