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Background: The literature on the association between subjective effects (SEs; i.e., how an individual perceives their physiological and psychological reactions to a drug) and substance use disorders (SUDs) is largely limited to community samples. The present study addressed the following aims in a clinical sample: whether SEs predict general versus substance-specific SUD in adolescence and adulthood after controlling for conduct disorder symptoms (CDsymp); whether SEs predict SUDs across drug classes; whether SEs predict change in SUD from adolescence to adulthood; and whether there are racial/ethnic differences in associations., Methods: Longitudinal analyses were conducted using data from a sample of 744 clinical probands recruited from residential and outpatient SUD treatment facilities in CO during adolescence (M age = 16.26) and re-assessed twice in adulthood (M ages = 22.56 and 28.96), approximately seven and twelve years after first assessment. SEs and CDsymp were assessed in adolescence. SUD severity was assessed at adolescence and twice during adulthood., Results: SEs assessed in adolescence robustly predicted general SUD for legal and illegal substances in adolescence and adulthood, whereas CDsymp predicted SUD primarily in adolescence. Higher positive and negative SEs in adolescence were associated with greater SUD severity after controlling for CDsymp, with similar magnitudes. Results indicated cross-substance effects of SEs on SUD. We found no evidence for racial/ethnic differences in associations., Conclusions: We investigated the progression of SUD in a high-risk sample with greater odds of sustained SUD. In contrast to CDsymp, both positive and negative SEs consistently predicted general SUD across substances in adolescence and adulthood., Competing Interests: Declaration of Competing Interest No conflict declared., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background and Aims: Adolescents with conduct and substance use problems are at increased risk for premature mortality, but the extent to which these risk factors reflect family- or individual-level differences and account for shared or unique variance is unknown. This study examined common and independent contributions to mortality hazard in adolescents ascertained for conduct disorder (CD) and substance use disorder (SUD), their siblings and community controls, hypothesizing that individual differences in CD and SUD severity would explain unique variation in mortality risk beyond that due to clinical/control status and demographic factors., Design: Mortality analysis in a prospective study (Genetics of Antisocial Drug Dependence Study) that began in 1993., Setting: Multi-site sample recruited in San Diego, California and Denver, Colorado, USA., Participants: A total of 1463 clinical probands were recruited through the juvenile correctional system, court-mandated substance abuse treatment programs and correctional schools, along with 1399 of their siblings, and 904 controls., Measurements: Mortality and cause-of-death were assessed via National Death Index search (released October, 2017)., Findings: There were 104 deaths documented among 3766 (1168 female) adolescents and young adults (average age 16.79 years at assessment, 32.69 years at death/censoring). Mortality hazard for clinical probands and their siblings was 4.99 times greater than that of controls (95% confidence interval = 2.40-10.40; P < 0.001). After accounting for demographic characteristics, site, clinical status, familial dependence and shared contributions of CD and SUD, CD independently predicted mortality hazard, whereas SUD severity did not., Conclusions: In the United States, youth with conduct and substance use disorders and their siblings face far greater risk of premature death than demographically similar community controls. In contrast to substance use disorder severity, conduct disorder is a robust predictor of unique variance in all-cause mortality hazard beyond other risk factors., (© 2018 Society for the Study of Addiction.)

Externalizing problems (EP), including rule-breaking, aggression, and criminal involvement, are highly prevalent during adolescence, but the adult outcomes of adolescents exhibiting EP are characterized by heterogeneity. Although many youths' EP subside after adolescence, others' persists into adulthood. Characterizing the development of severe EP is essential to prevention and intervention efforts. Multiple predictors of adult antisocial personality disorder (ASPD) and legal outcomes of a large sample (N = 1205) of clinically- or legally-ascertained adolescents (ages 12-19 years) with severe EP were examined. Many psychosocial predictors hypothesized to predict persistence of EP demonstrated zero-order associations with adult outcomes, but accounted for little unique variation after accounting for baseline conduct disorder symptoms (CD) and demographic factors. Baseline measures of intelligence, which explained independent variation in legal outcomes, provided the only consistent exception to this pattern, though future work is needed to parse these effects from those of socioeconomic factors. CD severity during adolescence is a parsimonious index of liability for persistence of EP into adulthood that explains outcome variance above and beyond all other demographic and psychosocial predictors in this sample., Competing Interests: The authors have declared that no competing interests exist.

The present study tested specific hypotheses advanced by the developmental propensity model of the etiology of conduct problems in the Colorado Longitudinal Twin Study, a prospective, longitudinal, genetically informative sample. High negative emotionality, low behavioral inhibition, low concern and high disregard for others, and low cognitive ability assessed during toddlerhood (age 14 to 36 months) were examined as predictors of conduct problems in later childhood and adolescence (age 4 to 17 years). Each hypothesized antisocial propensity dimension predicted conduct problems, but some predictions may be context specific or due to method covariance. The most robust predictors were observed disregard for others (i.e., responding to others' distress with active, negative responses such as anger and hostility), general cognitive ability, and language ability, which were associated with conduct problems reported by parents, teachers, and adolescents, and change in observed negative emotionality (i.e., frustration tolerance), which was associated with conduct problems reported by teachers and adolescents. Furthermore, associations between the most robust early predictors and later conduct problems were influenced by the shared environment rather than genes. We conclude that shared environmental influences that promote disregard for others and detract from cognitive and language development during toddlerhood also predispose individuals to conduct problems in later childhood and adolescence. The identification of those shared environmental influences common to early antisocial propensity and later conduct problems is an important future direction, and additional developmental behavior genetic studies examining the interaction between children's characteristics and socializing influences on conduct problems are needed. (PsycINFO Database Record, ((c) 2016 APA, all rights reserved).)

Major depressive disorder (MDD) is a prevalent and frequently comorbid psychiatric disorder. This study evaluates the development of depressive symptoms, MDD diagnosis, and suicidal ideation in a high-risk sample (N=524) diagnosed with conduct disorder (CD) and substance use disorder (SUD) symptoms as youth and re-assessed approximately 6.5 years later. Dual trajectory classes of both alcohol and other drug use (AOD) and antisocial behavior (ASB), previously identified using latent class growth analyses (LCGA), were used to predict depression outcomes. The Dual Chronic, Increasing AOD/Persistent ASB, and Decreasing Drugs/Persistent ASB classes had higher past-week depression scores, more past-year MDD symptoms, and were more likely to have past-year MDD than the Resolved class. The Dual Chronic and Decreasing Drugs/Persistent ASB classes also had more past-year MDD symptoms than the Persistent AOD/Adolescent ASB class. Youth at highest risk for developing or maintaining depression in adulthood had the common characteristic of persistent antisocial behavior. This suggests young adulthood depression is associated more with persistent antisocial behavior than with persistent substance use in comorbid youth. As such, interventions targeting high-risk youth, particularly those with persistent antisocial behavior, are needed to help reduce the risk of severe psychosocial consequences (including risk for suicide) in adulthood., (Published by Elsevier Ireland Ltd.)

Previous studies have shown associations between single nucleotide polymorphisms (SNPs) in gamma aminobutyric acid receptor alpha 2 (GABRA2) and adolescent conduct disorder (CD) and alcohol dependence in adulthood, but not adolescent alcohol dependence. The present study was intended as a replication and extension of this work, focusing on adolescent CD, adolescent alcohol abuse and dependence (AAD), and adult AAD. Family based association tests were run using Hispanics and non-Hispanic European American subjects from two independent longitudinal samples. Although the analysis provided nominal support for an association with rs9291283 and AAD in adulthood and CD in adolescence, the current study failed to replicate previous associations between two well replicated GABRA2 SNPs and CD and alcohol dependence. Overall, these results emphasize the utility of including an independent replication sample in the study design, so that the results from an individual sample can be weighted in the context of its reproducibility.

Objective: To examine the influence of conduct disorder (CD) on substance use initiation., Method: Community adolescents without CD (n = 1,165, mean baseline age = 14.6 years), with CD (n = 194, mean baseline age = 15.3 years), and youth with CD recruited from treatment (n = 268, mean baseline age = 15.7 years) were prospectively followed and re-interviewed during young adulthood (mean ages at follow-up respectively: 20, 20.8, and 24). Young adult retrospective reports of age of substance initiation for 10 substance classes were analyzed using Cox regression analyses. Hazard ratios of initiation for the CD cohorts (community without CD as the reference) at ages 15, 18, and 21 were calculated, adjusting for baseline age, gender, and race/ethnicity., Results: Among community subjects, CD was associated with elevated adjusted hazards for initiation of all substances, with comparatively greater hazard ratios of initiating illicit substances at age 15 years. By age 18, the adjusted hazard ratios remained significant except for alcohol. At age 21, the adjusted hazard ratios were significant only for cocaine, amphetamines, inhalants, and club drugs. A substantial portion of community subjects without CD never initiated illicit substance use. Clinical youth with CD demonstrated similar patterns, with comparatively larger adjusted hazard ratios., Conclusions: CD confers increased risk for substance use initiation across all substance classes at age 15 years, with greater relative risk for illicit substances compared to licit substances. This effect continues until age 18 years, with the weakest effect for alcohol. It further diminishes for other substances by age 21, However, the likelihood of initiating cocaine, amphetamines, inhalants and club drug use among those who have not initiated yet continues to be highly elevated by age 21., (Copyright © 2013 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Animal and human studies have implicated oxytocin in affiliative and prosocial behaviors. We tested whether genetic variation in the oxytocin receptor (OXTR) gene is associated with conduct disorder (CD). Utilizing a family-based sample of adolescent probands recruited from an adolescent substance abuse treatment program, control probands and their families (total sample, n=1750), we conducted three tests of association with CD and 10 single nucleotide polymorphisms (SNPs) in the OXTR gene: (a) family-based comparison utilizing the entire sample; (b) within-Whites, case-control comparison of adolescent patients with CD and controls without CD; and (c) within-Whites case-control comparison of parents of patients and parents of controls. Family-based association tests failed to show significant results (no results P<0.05). While strictly correcting for the number of tests (α=0.002), adolescent patients with CD did not differ significantly from adolescent controls in genotype frequency for the OXTR SNPs tested; similarly, comparison of OXTR genotype frequencies for parents failed to differentiate patient and control family type, except a trend association for rs237889 (P=0.004). We concluded that in this sample, 10 SNPs in the OXTR gene were not significantly associated with CD.

Background: Conduct disorder is a serious, relatively common disorder of childhood and adolescence. Findings from genetic association studies searching for genetic determinants of the liability toward such behaviors have been inconsistent. One possible explanation for differential results is that most studies define phenotype from a single assessment; for many adolescents conduct problems decrease in severity over time, whereas for others such behaviors persist. Therefore, longitudinal datasets offer the opportunity to refine phenotype., Methods: We used Caucasians that were first assessed during adolescence from the National Youth Survey Family Study. Nine waves of data were used to create latent growth trajectories and test for associations between trajectory class and 5HTTLPR genotype., Results: For the full sample, 5HTTLPR was not associated with conduct problem phenotypes. However, the short (s) allele was associated with chronic conduct problems in females; a nominally significant sex by 5HTTLPR genotype interaction was noted., Conclusion: Longitudinal studies provide unique opportunities for phenotypic refinement and such techniques, with large samples, may be useful for phenotypic definition with other study designs, such as whole genome association studies.

Theory and empirical evidence suggest that children's genetically influenced characteristics help to shape the environments they experience, including the parenting they 'receive'. The extent of these genetically-mediated child effects on childhood maltreatment is not well known. The present study estimates the magnitude of genetically mediated child effects on maltreatment in 3,297 twins and siblings who were part of a large nationally representative sample of adolescents (ADD health). Participants in early adulthood retrospectively reported their experiences of physical and sexual maltreatment and neglect. Results are consistent with small genetically-mediated child effects on physical maltreatment and neglect, and none on sexual maltreatment, and all three forms of maltreatment are influenced mainly by idiosyncratic individual circumstances.

Behavioral disinhibition has been characterized as a generalized vulnerability to externalizing disorders. Despite increasing evidence for its validity and heritability, the structural stability of behavioral disinhibition across adolescence and the strength and etiology of its relation to executive functions have not been studied. In this multivariate twin study, the authors assessed behavioral disinhibition using measures tapping substance use, conduct disorder, attention-deficit/hyperactivity disorder (ADHD), and novelty seeking at ages 12 and 17. Executive functions were assessed with laboratory-based cognitive tasks at age 17. Results indicated that, at age 12, behavioral disinhibition was dominated by ADHD and conduct problems and was highly heritable. At age 17, the contributions of the 4 components were more balanced, and the proportion of variance attributable to genetic factors was somewhat smaller, with additional variance due to shared environmental influences. At both ages, behavioral disinhibition was more closely related to response inhibition than other executive functions (working memory updating and task-set shifting), and this relationship was primarily genetic in origin. These results highlight the dynamic nature of behavioral disinhibition across adolescence and suggest that response inhibition may be an important mechanism underlying vulnerability to disinhibitory psychopathology.

Objective: We examined DSM-IV conduct disorder (CD) symptom criteria in a community sample of male and female adolescents to evaluate the extent to which DSM-IV criteria characterize the range of severity of adolescent antisocial behavior within and across sex., Method: Interviews were conducted with 3,208 adolescents between the ages of 11 and 18 years using the Diagnostic Interview Schedule for Children. Item response theory analyses were performed to obtain severity and discrimination parameters for each of the lifetime DSM-IV CD symptom criteria. In addition, item response theory-based differential item functioning analyses were conducted to examine the extent to which the symptom criteria function similarly across sex., Results: The DSM-IV CD symptom criteria are useful and meaningful indicators of severe adolescent antisocial behavior. A single item ("Steal without Confrontation") was a poor indicator of severe antisocial behavior. The CD symptom criteria function similarly across sex; however, three items had significantly different severity parameters., Conclusions: The DSM-IV CD criteria are informative as categorical and continuous measures of severe adolescent antisocial behavior; however, some CD criteria display sex bias.

The evidence for common genetic and environmental influences on conduct disorder (CD) and major depressive disorder (MDD) in adolescents was examined. A sample of 570 monozygotic twin pairs, 592 dizygotic twin pairs, and 426 non-twin siblings, aged 12-18 years, was recruited from the Colorado Twin Registry. For the past year data, there was a significant correlation between the genetic influences on MDD and CD and, for the lifetime data, there was a significant correlation between the genetic influences on MDD and CD, and a significant correlation between the nonshared environmental influences on MDD and CD. Our results suggest that some genetic factors will increase an individual's vulnerability to both MDD and CD in adolescence.

Many putative environmental risks correlate with individuals' genotypes. The association between delinquent peer affiliation and conduct problems may occur because of shared genetic liability. Five hundred fifty three monozygotic and 558 dizygotic twin pairs, aged 11 to 18 years, were assessed for delinquent peer affiliation and conduct problems. The authors investigated whether genes contribute to both delinquent peer affiliation and the correlation between delinquent peer affiliations and conduct problems. Delinquent peer affiliation was influenced by genetic, shared environmental, and nonshared environmental factors; genetic factors also contributed to the correlation between delinquent peer affiliations and conduct problems, providing evidence for genotype-environment correlation. The magnitude of the genetic variance of conduct problems was contextually dependent on levels of delinquent peer affiliation and was greater at higher levels of delinquent peer affiliation., ((c) 2007 APA, all rights reserved)

This study explores the association between a highly heritable behavioral disinhibition phenotype and the protein kinase C gamma (PRKCG) gene in an ethnically diverse youth sample from Colorado, USA. The rationale for this study was based on the impulsive behavior and increased ethanol consumption observed in the protein kinase C gamma (PKC-gamma)-deficient mouse model. Two composite behavioral disinhibition phenotypes and their component behavioral scores [conduct disorder, attention-deficit hyperactivity disorder (ADHD), substance experimentation (SUB) and novelty-seeking] were examined for association with five independent PRKCG single nucleotide polymorphisms (SNPs). Association analysis for the five individual SNPs revealed modest genetic association of Exon 14 (rs2242244) and Upstream (rs307941) markers with the behavioral disinhibition composite variables in the combined, Hispanic and African-American samples. Additionally, haplotype-based association analysis for two SNPs located in Intron 3 (rs402691) and Exon 6 (rs3745406) indicated a significant overall association of the PRKCG locus with the ADHD-hyperactive subscale scores in the combined and Caucasian samples, supporting the relation between impulsive behaviors and the PRKCG gene. A significant haplotype association was also observed with SUB scores but only in the Hispanic ethnic group, highlighting the marker variability for each ethnic group. In conclusion, our results support the role of the PKC-gamma enzyme in behavioral impulsivity previously observed in mice. This study provides the first exploration of the PRKCG gene and its association with behavioral disinhibition and warrants further study in other larger population samples.

Background: Conduct disorder (CD), alcohol dependence (AD), and illicit drug dependence (IDD) frequently co-occur. This paper describes the result of an investigation of the extent to which comorbid alcohol and illicit drug dependence in adolescents are explained by etiological factors in common with conduct disorder., Methods: Participants were 645 MZ twin pairs, 702 DZ twin pairs, 429 biological sibling pairs, and 96 adoptive sibling pairs, aged 12-18 years, from a community based sample. Conduct disorder was measured using the Diagnostic Interview Schedule for Children-IV. Alcohol and illicit drug dependence were assessed using the Composite International Diagnostic Interview-Substance Abuse Module (CIDI-SAM). For each outcome, subjects were categorized into those with no symptoms, those with one or more symptoms but no diagnosis, and those with a diagnosis., Results: The heritability estimates for CD, AD, and IDD were 58, 66, and 36%, respectively. The genetic correlation between AD and IDD was partially explained by the genetic risk they both share with conduct disorder., Conclusions: We conclude that conduct disorder in adolescents explains, in part, the co-occurrence of alcohol and illicit drug dependence. Specifically, the genetic contribution to their covariation is explained partially by the genetic contribution in common with conduct disorder.

Objective: Childhood maltreatment is a potent risk factor for subsequent aggressive and criminal behavior. A recent study suggested that the relationship between maltreatment and antisocial behavior may be moderated by a genetic vulnerability conferred by a functional polymorphism in the MAO-A gene. The authors investigated whether these findings would generalize to a clinical cohort of adolescents, examining whether there was a stronger association between maltreatment and conduct disorder severity in patients carrying the low MAO-A activity allele., Method: Male adolescent patients (N=247) entering residential or intensive day treatment for persistent conduct and substance use problems were examined. Conduct disorder severity was indexed by a lifetime count of DSM-IV criteria obtained through structured psychiatric interviews. Maltreatment scores were derived from summing neglect and abuse events reported to have occurred before age 11., Results: Neglect, verbal/psychological abuse, physical abuse, and sexual abuse were prevalent among patients. Although level of maltreatment and lifetime conduct disorder symptoms were significantly correlated, no genetic-environmental interaction with genotype for maltreatment was found., Conclusion: The results of the current study do not support the hypothesis that a polymorphism in the gene encoding MAO-A contributes to the genetic risk for conduct disorder.

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.

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.

Major depressive disorder (MDD) is a prevalent and frequently comorbid psychiatric disorder. This study evaluates the development of depressive symptoms, MDD diagnosis, and suicidal ideation in a high-risk sample (N=524) diagnosed with conduct disorder (CD) and substance use disorder (SUD) symptoms as youth and re-assessed approximately 6.5 years later. Dual trajectory classes of both alcohol and other drug use (AOD) and antisocial behavior (ASB), previously identified using latent class growth analyses (LCGA), were used to predict depression outcomes. The Dual Chronic, Increasing AOD/Persistent ASB, and Decreasing Drugs/Persistent ASB classes had higher past-week depression scores, more past-year MDD symptoms, and were more likely to have past-year MDD than the Resolved class. The Dual Chronic and Decreasing Drugs/Persistent ASB classes also had more past-year MDD symptoms than the Persistent AOD/Adolescent ASB class. Youth at highest risk for developing or maintaining depression in adulthood had the common characteristic of persistent antisocial behavior. This suggests young adulthood depression is associated more with persistent antisocial behavior than with persistent substance use in comorbid youth. As such, interventions targeting high-risk youth, particularly those with persistent antisocial behavior, are needed to help reduce the risk of severe psychosocial consequences (including risk for suicide) in adulthood.

Behavioral disinhibition (BD) is a quantitative measure designed to capture the heritable variation encompassing risky and impulsive behaviors. As a result, BD represents an ideal target for discovering genetic loci that predispose individuals to a wide range of antisocial behaviors and substance misuse that together represent a large cost to society as a whole. Published genome-wide association studies (GWAS) have examined specific phenotypes that fall under the umbrella of BD (e.g. alcohol dependence, conduct disorder); however no GWAS has specifically examined the overall BD construct. We conducted a GWAS of BD using a sample of 1,901 adolescents over-selected for characteristics that define high BD, such as substance and antisocial behavior problems, finding no individual locus that surpassed genome-wide significance. Although no single SNP was significantly associated with BD, restricted maximum likelihood analysis estimated that 49.3 % of the variance in BD within the Caucasian sub-sample was accounted for by the genotyped SNPs (p = 0.06). Gene-based tests identified seven genes associated with BD (p ≤ 2.0 × 10(-6)). Although the current study was unable to identify specific SNPs or pathways with replicable effects on BD, the substantial sample variance that could be explained by all genotyped SNPs suggests that larger studies could successfully identify common variants associated with BD.

Lower self-control is a significant correlate or predictor of a wide range of adult outcomes, and this association may be due to more general tendencies toward childhood externalizing problems. The present study examined the association between toddlerhood self-control expressed within a "don't" compliance task (at 14-36 months) and later externalizing problems (parent-reported externalizing problems from age 4 to 12 years, teacher-reported externalizing problems from age 7 to 12 years, and self-reported conduct disorder symptoms at age 17 years) in a longitudinal, genetically informative study. The slope of self-control, but not its intercept, predicted later teacher-reported, but not parent- or self-reported, externalizing problems. That is, increase in self-control during toddlerhood was associated with lower levels of later teacher-reported externalizing problems. The slope of self-control was no longer a significant predictor of teacher-reported externalizing problems after controlling for observed disregard for others, a robust predictor of externalizing problems. Thus, the hypothesis that self-control is the primary predictor of externalizing problems was not supported. Results from genetic analyses suggested that the covariance between the slope of self-control and teacher-reported externalizing problems is due to both genetic and shared environmental influences. [ABSTRACT FROM AUTHOR]

Several recent studies have reported an association between the serotonin transporter 5HTTLPR (s-allele) and aggression; however, nonreplications have also been reported. Inconsistencies may be explained by gene-environment interactions. Using a large general population sample, we sought to test for an association between 5HTTLPR and conduct problems, and to explore for a possible 5HTTLPR by maltreatment interaction.Using Caucasian adolescents from the genetic-pairs sample of the National Longitudinal Study of Adolescent Health (n=1736), we tested for an association between 5HTTLPR and both a categorical and, separately, a continuous measure of conduct problems using regression analyses while controlling for sex, family effects, and age. We then tested for an association between 5HTTLPR and conduct problems using the within-family test Quantitative Transmission Disequilibrium Test. Analyses were repeated for a measure of adolescence-limited delinquency.Results did not support an association between 5HTTLPR and conduct problems or delinquency. The Quantitative Transmission Disequilibrium Test analyses, which account for population stratification, were nonsignificant (F=0.17; P=0.68); introducing maltreatment as a covariate into the model did not affect this association (F=0.17; P=0.68). No association was seen between 5HTTLPR and a measure of adolescence-limited delinquency (F=0.54; P=0.46).Using two methods in a large general population sample we did not find a significant association between 5HTTLPR and conduct problems. A gene by maltreatment interaction was not supported. [ABSTRACT FROM AUTHOR]

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 deliquency 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. [ABSTRACT FROM AUTHOR]

In this report we characterize associations between parental psychiatric disorders and children's psychiatric symptoms and disorders using a population-based sample of 850 twin families. Juvenile twins are aged 8-17 years and are personally interviewed about their current history of DSM-III-R conduct, depression, oppositional-defiant, overanxious, and separation anxiety disorders using the CAPA-C. Mothers and fathers of twins are personally interviewed about their lifetime history of DSM-III-R alcoholism, antisocial personality disorder, generalized anxiety disorder, major depression, panic disorder/agoraphobia, social phobia, and simple phobia using a modified version of the SCID and the DIS. Generalized least squares and logistic regression are used to identify the juvenile symptoms and disorders that are significantly associated with parental psychiatric histories. The specificity of these associations is subsequently explored in a subset of families with maternal, plus parental psychiatric histories with a prevalence > 1%. Parental depression that is not comorbid or associated with a different spousal disorder is associated with a significantly elevated level of depression and overanxious disorder symptoms and a significantly increased risk for overanxious disorder. Risks are higher for both symptomatic domains in association with maternal than paternal depression, and highest in association with maternal plus paternal depression. Risks for other juvenile symptoms and disorders index the comorbid and spousal histories with which parental depression is commonly associated. Paternal alcoholism that is not comorbid or associated with a maternal disorder is not significantly associated with current psychiatric symptoms or disorders in offspring. Risks for oppositional-defiant or conduct symptoms/disorders in the offspring of alcoholic parents index parental comorbidity and/or other spousal histories. [ABSTRACT FROM AUTHOR]

We introduce an overlapping cohort sequential longitudinal study of behavioral development and psychopathology in a representative sample of 1412 pairs of twins aged 8 through 16 years. Multiple phenotypic assessments involve a full psychiatric interview with each child and each parent, and supplementary parental, teacher, and child interview material and questionnaires. For the first wave of assessments, the numbers of reported DSM-III-R symptoms of Major Depressive Disorder (MDD), Separation Anxiety Disorder (SAD), Overanxious Disorder (OAD), Oppositional Defiant Disorder (ODD), Conduct Disorder (CD), and Attention Deficit Hyperactivity Disorder (ADHD), assessed through interviews, confirm patterns of age and sex trends found in other epidemiological samples, but underscore their dependence on whether the child or the parent is the informant. Correlations across domains for symptoms reported by the same informant are often as large as correlations across informants for the same domain of symptoms. Factor analyses of these symptom counts, taking account of informant view and unreliability of assessment, show the high degree of correlation between SAD and OAD, between MDD and OAD, and between CD and ODD. ADHD symptoms are relatively independent of the other domains, but show moderate correlations with CD, ODD, and MDD. Factorially derived dimensional questionnaire scales, based on child, parental, and teacher reports, show patterns of relationship to symptom counts consistent with both convergent and discriminant validity as indices of liability to clinical symptoms. Across informants, questionnaire scales provide as good a prediction of symptoms as do clinical interviews. Multitrait-multimethod confirmatory factor analysis reveals the patterns of relationship between symptoms of psychiatric disorder in children taking due account of informant and unique sources of variance. Gender differences are consistent within the correlated clusters of ODD/CD and MDD/SAD/OAD, although there are disorder-specific age trends. There are large informant-specific influences on the reporting of symptoms in clinical interviews. Dimensional questionnaire scales provide a useful source of additional information. In subsequent analyses of genetic and environmental etiology of childhood psychopathology we must expect that results may differ by informant and method of assessment. Multivariate and developmental analyses that explore the sources of these differences will shed new light on the relationship between genetic and environmentally influenced vulnerability and the manifestation of psychopathology in specific circumstances. [ABSTRACT FROM AUTHOR]

Background: A promoter polymorphism in the serotonin transporter (5HTTLPR) has functional effects on an important physiologic process involved in serotonin (5HT) signaling. Despite the fact that variation in the 5HT system has long been implicated in the etiology of aggressive behaviors, only a few association-based studies with mixed results have been reported. Methods: We conducted family-based tests of association in a sample of 366 families from which 1187 genotypes of the 5HTTLPR were generated using polymerase chain reaction. Ratings of aggressive behavior were obtained from parents and teachers longitudinally using the Child Behavior Checklist (CBCL) and Teacher Report Form (TRF), instruments widely used in behavioral and psychiatric genetics. Results: Within-family tests suggest an association between the s-allele of the 5HTTLPR and higher aggressive behavior in middle childhood. The strongest association was at age 9 and for an aggregate measure of teacher-rated aggressive behavior. Conclusions: This is the first report of an association analysis of the 5HTTLPR in a general population sample of school-age children. The results provide some support for the hypothesis that the functional effects of the 5HTTLPR s-allele are associated with higher levels of aggressive behavior in middle childhood. [Copyright &y& Elsevier]

Abstract: Objective: To identify robust predictors of drug dependence. Methods: This longitudinal study included 2361 male and female twins from an ongoing longitudinal study at the Center for Antisocial Drug Dependence (CADD) at the University of Colorado Boulder and Denver campuses. Twins were recruited for the CADD project while they were between the ages of 12 and 18. Participants in the current study were on average approximately 15years of age during the first wave of assessment and approximately 20years of age at the second wave of assessment. The average time between assessments was five years. A structured interview was administered at each assessment to determine patterns of substance use and Diagnostic and Statistical Manual of Mental Disorders (DSM-IV; Fourth Edition) attention deficit hyperactivity disorder (ADHD), conduct disorder (CD), and drug dependence symptoms. Cloninger's Tridimensional Personality Questionnaire was also used to assess novelty seeking tendencies (NS). At the second wave of assessment, DSM-IV dependence symptoms were reassessed using the same interview. Path analyses were used to examine direct and indirect mechanisms linking psychopathology and drug outcomes. Results: Adolescent substance use, CD, and NS predicted young adult substance dependence, whereas the predictive effects of ADHD were few and inconsistent. Furthermore, CD and NS effects were partially mediated by adolescent substance use. Conclusions: Adolescent conduct problems, novelty seeking, and drug use are important indices of future drug problems. The strongest predictor was novelty seeking. [Copyright &y& Elsevier]

Background: A functional promoter polymorphism in monoamine oxidase A (MAOA) has been implicated as a moderating factor in the relationship between childhood maltreatment and later adolescent and adult antisocial behavior. Despite wide interest in this hypothesis, results remain mixed from the few attempts at replication. Methods: Regression-based analyses were conducted to test for a genotype-environment interaction using self-reported physical abuse and MAOA genotype to predict later antisocial behavior and arrests for violence by participants in the National Youth Survey Family Study. We also examined the interaction using a measure of violent victimization. The analysis sample included 277 Caucasian male respondents, aged 11–15 in 1976, who provided buccal swab DNA samples and who were successfully genotyped for the variable number tandem repeat (VNTR) in the MAOA promoter using polymerase chain reaction. Results: Maltreatment by a parent during adolescence was a risk factor for adolescent and adult antisocial and violence related behavioral problems. Tests for the main effect of MAOA and a MAOA-maltreatment interaction were nonsignificant. Similar results were obtained using the measure of adolescent violent victimization. Conclusions: Findings from this general population sample could not confirm the hypothesis that MAOA moderates the relationship between adolescent maltreatment and adolescent or adult antisocial behavior. [Copyright &y& Elsevier]

Objective: To explore the genetic and environmental influences on DSM-IV conduct disorder (CD) aggressive and nonaggressive subscales, taking into account age and sex differences.Method: A community sample of 1,100 twin pairs (ages 11-18) was interviewed using the Diagnostic Interview Schedule for Children. Bivariate analyses, using variable threshold models accounting for age and sex differences, were used to determine the extent to which the genetic and environmental influences on aggressive and nonaggressive CD domains are shared or unique.Results: The phenotypic correlation between aggressive and nonaggressive CD domains was 0.32. The most parsimonious bivariate model included additive genetic effects and nonshared environmental effects only (AE model).Conclusions: The results of behavior genetic model fitting suggest that the DSM-IV CD domains are influenced by unique genetic and environmental factors, but also share some common genetic and environmental influences. A large percentage of the covariation (61%) is caused by genetic factors. These results are consistent with a previous report on the bivariate heritability of aggressive and nonaggressive antisocial behavior, but extend the findings to DSM-IV domains. [ABSTRACT FROM AUTHOR]