Associations between childhood ADHD, gender, and adolescent alcohol and marijuana involvement: A causally informative design.

BACKGROUND: We report whether the etiology underlying associations of childhood ADHD with adolescent alcohol and marijuana involvement is consistent with causal relationships or shared predispositions, and whether it differs by gender. METHODS: In three population-based twin samples (N = 3762; 64% monozygotic), including one oversampling females with ADHD, regressions were conducted with childhood inattentive or hyperactive-impulsive symptoms predicting alcohol and marijuana outcomes by age 17. To determine whether ADHD effects were consistent with causality, twin difference analyses divided effects into those shared between twins in the pair and those differing within pairs. RESULTS: Adolescents with more severe childhood ADHD were more likely to initiate alcohol and marijuana use earlier, escalate to frequent or heavy use, and develop symptoms. While risks were similar across genders, females with more hyperactivity-impulsivity had higher alcohol consumption and progressed further toward daily marijuana use than did males. Monozygotic twins with more severe ADHD than their co-twins did not differ significantly on alcohol or marijuana outcomes, however, suggesting a non-causal relationship. When co-occurring use of other substances and conduct/oppositional defiant disorders were considered, hyperactivity-impulsivity remained significantly associated with both substances, as did inattention with marijuana, but not alcohol. CONCLUSIONS: Childhood ADHD predicts when alcohol and marijuana use are initiated and how quickly use escalates. Shared familial environment and genetics, rather than causal influences, primarily account for these associations. Stronger relationships between hyperactivity-impulsivity and heavy drinking/frequent marijuana use among adolescent females than males, as well as the greater salience of inattention for marijuana, merit further investigation.

Increased Risk of Smoking in Female Adolescents Who Had Childhood ADHD.

OBJECTIVE: This study examined the effects of childhood attention deficit hyperactivity disorder (ADHD) symptoms, both inattention and hyperactivity-impulsivity, on the development of smoking in male and female adolescents. METHOD: Twin difference methods were used to control for shared genetic and environmental confounders in three population-based, same-sex twin samples (N=3,762; 64% monozygotic). One cohort oversampled female adolescents with ADHD beginning in childhood. Regressions of childhood inattentive and hyperactive-impulsive symptoms were conducted to predict smoking outcomes by age 17. ADHD effects were divided into those shared between twins in the pair and those nonshared, or different within pairs. RESULTS: Adolescents who had more severe ADHD symptoms as children were more likely to initiate smoking and to start smoking younger. The association of ADHD symptoms with daily smoking, number of cigarettes per day, and nicotine dependence was greater in females than in males. Monozygotic female twins with greater attentional problems than their co-twins had greater nicotine involvement, consistent with possible causal influence. These effects remained when co-occurring externalizing behaviors and stimulant medication were considered. Hyperactivity-impulsivity, while also more strongly related to smoking for female adolescents, appeared primarily noncausal. CONCLUSIONS: Smoking initiation and escalation are affected differentially by ADHD subtype and gender. The association of inattention with smoking in female adolescents may be causal, whereas hyperactivity-impulsivity appears to act indirectly, through shared propensities for both ADHD and smoking.

Antisocial peer affiliation and externalizing disorders: Evidence for Gene × Environment × Development interaction.

Gene × Environment interaction contributes to externalizing disorders in childhood and adolescence, but little is known about whether such effects are long lasting or present in adulthood. We examined gene-environment interplay in the concurrent and prospective associations between antisocial peer affiliation and externalizing disorders (antisocial behavior and substance use disorders) at ages 17, 20, 24, and 29. The sample included 1,382 same-sex twin pairs participating in the Minnesota Twin Family Study. We detected a Gene × Environment interaction at age 17, such that additive genetic influences on antisocial behavior and substance use disorders were greater in the context of greater antisocial peer affiliation. This Gene × Environment interaction was not present for antisocial behavior symptoms after age 17, but it was for substance use disorder symptoms through age 29 (though effect sizes were largest at age 17). The results suggest adolescence is a critical period for the development of externalizing disorders wherein exposure to greater environmental adversity is associated with a greater expression of genetic risk. This form of Gene × Environment interaction may persist through young adulthood for substance use disorders, but it appears to be limited to adolescence for antisocial behavior.

A Test-Replicate Approach to Candidate Gene Research on Addiction and Externalizing Disorders: A Collaboration Across Five Longitudinal Studies.

This study presents results from a collaboration across five longitudinal studies seeking to test and replicate models of gene-environment interplay in the development of substance use and externalizing disorders (SUDs, EXT). We describe an overview of our conceptual models, plan for gene-environment interplay analyses, and present main effects results evaluating six candidate genes potentially relevant to SUDs and EXT (MAOA, 5-HTTLPR, COMT, DRD2, DAT1, and DRD4). All samples included rich longitudinal and phenotypic measurements from childhood/adolescence (ages 5-13) through early adulthood (ages 25-33); sample sizes ranged from 3487 in the test sample, to ~600-1000 in the replication samples. Phenotypes included lifetime symptom counts of SUDs (nicotine, alcohol and cannabis), adult antisocial behavior, and an aggregate externalizing disorder composite. Covariates included the first 10 ancestral principal components computed using all autosomal markers in subjects across the data sets, and age at the most recent assessment. Sex, ancestry, and exposure effects were thoroughly evaluated. After correcting for multiple testing, only one significant main effect was found in the test sample, but it was not replicated. Implications for subsequent gene-environment interplay analyses are discussed.

Parent involvement, sibling companionship, and adolescent substance use: A longitudinal, genetically informed design.

A large literature shows that parent and sibling relationship factors are associated with an increased likelihood of adolescent substance use. Less is known about the etiology of these associations. Using a genetically informed sibling design, we examined the prospective associations between parent involvement, sibling companionship, and adolescent substance use at 2 points in mid- and late-adolescence. Adolescents were adopted (n = 568) or the biological offspring of both parents (n = 412). Cross-lagged panel results showed that higher levels of parent involvement in early adolescence were associated with lower levels of substance use later in adolescence. Results did not significantly differ across adoption status, suggesting this association cannot be due to passive gene-environment correlation. Adolescent substance use at Time 1 was not significantly associated with parent involvement at Time 2, suggesting this association does not appear to be solely due to evocative (i.e., "child-driven") effects either. Together, results support a protective influence of parent involvement on subsequent adolescent substance use that is environmental in nature. The cross-paths between sibling companionship and adolescent substance use were significant and negative in direction (i.e., protective) for sisters, but positive for brothers (in line with a social contagion hypothesis). These effects were consistent across genetically related and unrelated pairs, and thus appear to be environmentally mediated. For mixed gender siblings, results were consistent with environmentally driven, protective influence hypothesis for genetically unrelated pairs, but in line with a genetically influenced, social contagion hypothesis for genetically related pairs. Implications are discussed.

High School Sports Involvement Diminishes the Association Between Childhood Conduct Disorder and Adult Antisocial Behavior.

PURPOSE: Life course-persistent antisocial behavior manifests as a display of aggressive and antisocial behavior beginning in childhood (conduct disorder [CD]) and lasting through adulthood (adult antisocial personality disorder). This study aimed to build on prior research by evaluating whether involvement in high school sports helped attenuate the association between CD and subsequent adult antisocial behavior (AAB). METHODS: A prospective sample of 967 male and female adolescents (56% adopted) was used. Structured interviews were used to assess CD (symptoms before the age of 15 years), involvement in sports during high school, and past-year adult antisocial personality disorder symptoms in young adulthood (M age = 22.4 years). RESULTS: As expected, the association between CD and AAB was significantly less for those involved in sports (ß = .28; p < .001) compared with those not involved in sports (ß = .49; p < .001), χ(2)(1) = 4.13; p = .04. This difference remained after including known covariates of antisocial behavior in the model (age, gender, adoption status), and results were consistent across males and females. Involvement in other extracurricular activities (e.g., student government, plays, clubs) did not significantly moderate the relationship between CD and AAB. CONCLUSIONS: Although selection effects were evident (those with more CD symptoms were less likely to be involved in sports), findings nevertheless suggest high school sports involvement may be a notable factor related to disrupting persistent antisocial behavior beginning in childhood and adolescence and lasting through young adulthood. Implications are discussed.

The developmental progression of age 14 behavioral disinhibition, early age of sexual initiation, and subsequent sexual risk-taking behavior.

BACKGROUND: Research has demonstrated a consistent relationship between early sexual experience and subsequent sexual risk-taking behaviors. We hypothesized that this relationship is due to a general predisposition toward behavioral disinhibition (BD), and that relationships among BD, early sex, and subsequent risky sexual behavior may be influenced by common genetic influences for males and common environmental influences for females. METHODS: A prospective sample of 1,512 same-sex adolescent twins (50.2% female) was used. Adolescent BD was measured by clinical symptom counts of conduct disorder, oppositional defiant disorder, and self-reported delinquent behavior (age 14). Age of sexual initiation was defined as first age of consensual oral or penetrative sex (mean age ~17). Adult risky sexual behavior was defined by sexual behaviors under the influence of drugs and alcohol and number of casual sexual partners in the past year (age 24). RESULTS: Multivariate analyses showed evidence for substantial common genetic variance among age 14 BD, age at sexual initiation, and adult risky sexual behavior for males, but not females. There was no significant difference in the degree of common environmental influence on these variables for females compared to males. Notably, age of sexual initiation was not significantly correlated with age 24 risky sexual behavior for females. CONCLUSION: The relationship between early sex and later risky sex can be better understood through a general liability toward BD, which is influenced primarily by genetic factors for males. The association between age 14 BD and age of sexual initiation was influenced through a combination of genetic and environmental factors for females; however, age of sexual initiation does not appear to be a salient predictor of adult women's sexual risk-taking behavior. Findings suggest that prevention programs aimed at reducing sexual risk behavior might target youth exhibiting BD by age 14, particularly males. More research is needed on what predicts adult sexual risk-taking behavior for females.

General and specific predictors of nicotine and alcohol dependence in early adulthood: genetic and environmental influences.

OBJECTIVE: This study builds on previous work delineating a hierarchical model of family environmental risk in relation to a hierarchical model of externalizing disorders (EXTs) by evaluating for gene-environment interplay in these relationships. The associations between parent-child relationship quality (conflict, bonding, and management) and substance-specific adolescent family environments (parental/sibling tobacco/alcohol use) in relation to young adult EXTs (age ∼22 years nicotine, alcohol, and other drug dependence; antisocial and risky sexual behavior) were evaluated. METHOD: The sample included 533 adopted offspring and 323 biological offspring. Because adopted youth do not share genes with their parents, a significant association between parent-child relationship quality and EXTs would provide evidence against passive gene-environment correlation (rGE). Significant associations between parental tobacco/alcohol use in relation to offspring nicotine/alcohol dependence in the adopted offspring support common environmental influence. Significant associations detected for the biological offspring only suggest common genetic influence. RESULTS: For both adoptive and biological offspring, there was a significant association between parent-child relationship quality and EXTs. Parental tobacco/alcohol use was unrelated to EXTs. Sibling tobacco/alcohol use was related to EXTs, but only for the biological siblings. Parental tobacco use was associated with the residual variance in nicotine dependence in adopted offspring. CONCLUSIONS: Findings replicate a long-term influence of adolescent parent-child relationship quality on adult EXTs. Findings extend previous research by providing evidence against passive rGE in this association. The association between parental tobacco use and adult nicotine dependence appears to be environmentally mediated, but caution is warranted as we found this relationship only for adopted youth.

Risk of suicide attempt in adopted and nonadopted offspring.

OBJECTIVE: We asked whether adoption status represented a risk of suicide attempt for adopted and nonadopted offspring living in the United States. We also examined whether factors known to be associated with suicidal behavior would mediate the relationship between adoption status and suicide attempt. METHODS: Participants were drawn from the Sibling Interaction and Behavior Study, which included 692 adopted and 540 nonadopted offspring and was conducted at the University of Minnesota from 1998 to 2008. Adoptees were systematically ascertained from records of 3 large Minnesota adoption agencies; nonadoptees were ascertained from Minnesota birth records. Outcome measures were attempted suicide, reported by parent or offspring, and factors known to be associated with suicidal behavior including psychiatric disorder symptoms, personality traits, family environment, and academic disengagement. RESULTS: The odds of a reported suicide attempt were ~4 times greater in adoptees compared with nonadoptees (odds ratio: 4.23). After adjustment for factors associated with suicidal behavior, the odds of reporting a suicide attempt were reduced but remained significantly elevated (odds ratio: 3.70). CONCLUSIONS: The odds for reported suicide attempt are elevated in individuals who are adopted relative to those who are not adopted. The relationship between adoption status and suicide attempt is partially mediated by factors known to be associated with suicidal behavior. Continued study of the risk of suicide attempt in adopted offspring may inform the larger investigation of suicidality in all adolescents and young adults.

Peer deviance, alcohol expectancies, and adolescent alcohol use: explaining shared and nonshared environmental effects using an adoptive sibling pair design.

Previous research suggests adolescent alcohol use is largely influenced by environmental factors, yet little is known about the specific nature of this influence. We hypothesized that peer deviance and alcohol expectancies would be sources of environmental influence because both have been consistently and strongly correlated with adolescent alcohol use. The sample included 206 genetically related and 407 genetically unrelated sibling pairs assessed in mid-to-late adolescence. The heritability of adolescent alcohol use (e.g., frequency, quantity last 12 months) was minimal and not significantly different from zero. The associations among peer deviance, alcohol expectancies, and alcohol use were primarily due to shared environmental factors. Of special note, alcohol expectancies also significantly explained nonshared environmental influence on alcohol use. This study is one of few that have identified specific environmental variants of adolescent alcohol use while controlling for genetic influence.

Levels of risk: maternal-, middle childhood-, and neighborhood-level predictors of adolescent disinhibitory behaviors from a longitudinal birth cohort in the United States.

OBJECTIVE: Disruptive behavior in adolescence may indicate a broad vulnerability to disinhibition, which begins in childhood and culminates in adult externalizing psychopathology. We utilized prospective birth cohort data to assess childhood predictors of adolescent disinhibition. We also examined the effect of pre-adolescent fluctuation in cognitive ability. METHODS: Data were drawn from the Child Health and Development Study cohort, born 1961-1963; we used the subsample who participated in follow-up through adolescence (n=1752). Six indicators of behavioral disinhibition (BD), reported in adolescence, were analyzed as a count outcome. Predictor variables were drawn from several waves of data collection and included individual-, maternal-, and neighborhood-level measures. Cognitive ability was assessed with the Peabody Picture Vocabulary Test at two time points. Neighborhood characteristics were assessed using census data from 1970. RESULTS: Number of BD indicators was predicted by maternal characteristics at prenatal assessment (maternal age and alcohol consumption) and age-10 assessment (maternal smoking, education, and separation from father). Characteristics of the child that predicted BD included birth order and conduct problems in middle childhood. Neighborhood poverty did not predict BD. Regardless of initial cognitive ability score, movement to a higher quartile by adolescence was associated with lower BD, while movement to a lower quartile was associated with higher BD. CONCLUSION: Risk for adolescent BD exists prenatally and extends through middle childhood. Change in cognitive ability during pre-adolescence emerged as a potentially important factor that merits further investigation. A greater focus on the life course can aid in comprehensively understanding disruptive behavior emergence in adolescence.

The enrichment study of the Minnesota twin family study: increasing the yield of twin families at high risk for externalizing psychopathology.

The Enrichment Study (ES) was designed to extend the Minnesota Twin Family Study (MTFS) by oversampling 11-year-old twins at especially high risk for substance use disorders by virtue of having a childhood disruptive disorder. The sample was ascertained from Minnesota birth records. To identify high-risk twins, we conducted telephone screening interviews for parent-reported symptoms of attention-deficit/hyperactivity disorder (ADHD) and conduct disorder (CD) as well as indications of academic disengagement. Twins who exceeded a predetermined threshold were invited to participate. To facilitate comparison with the previously ascertained MTFS participants, a random sample of 11-year-old twins was also recruited. As part of the ES study, 499 twin pairs, and their parents, visited the University of Minnesota, where each participant completed a clinical interview, psychophysiological evaluation, and thorough assessment of environmental risk. We were highly successful in recruiting at-risk twins; 52% of the screened male twins and 41% of the screened females met criteria for a diagnosis of ADHD, CD, or oppositional defiant disorder (ODD). At the pair level, 63% of the screened pairs had at least one member with a childhood disruptive disorder. This article provides an overview of the study design and includes a review of recent findings using this sample of twins.

Family interactions in adoptive compared to nonadoptive families.

Despite the large and growing numbers of adoptive families, little research describes interactions in families with adopted adolescents. Yet, adopted adolescents' increased risk for adjustment problems, combined with the association between family interactions and adolescent adjustment in nonadoptive families, raises questions about differences in adoptive and nonadoptive family interactions. We compared observed and self-reported family interactions between 284 adoptive and 208 nonadoptive families and within 123 families with 1 adopted and 1 nonadopted adolescent. Adolescents averaged 14.9 years of age. Comparisons were made using analysis of variance incorporating hierarchical linear methods in SAS PROC MIXED to control family-related correlations in the data. Parents and children reported more conflict in adoptive families when compared with nonadoptive families. Families with 1 adopted and 1 nonadopted adolescent reported more conflict between parents and adopted adolescents. Observed parental behavior was similar across adoptive and nonadoptive children although adopted adolescents were less warm and, in families with 2 adopted children, more conflictual than nonadopted adolescents. These findings suggest a need for further investigation of the association between family interactions and adopted adolescent problem behavior.

The mental health of US adolescents adopted in infancy.

OBJECTIVE: To determine whether adopted adolescents are at excess risk for clinically relevant behavioral and emotional problems. DESIGN: We examined whether adopted and nonadopted adolescents differed on quantitative indicators of mental health and the prevalence of childhood disorders and whether differences exist between internationally and domestically placed adoptees. SETTING: Assessments occurred at the University of Minnesota from December 11, 1998, to June 4, 2004. PARTICIPANTS: Adolescents adopted in infancy were systematically ascertained from records of 3 large Minnesota adoption agencies; nonadopted adolescents were ascertained from Minnesota birth records. The final sample included these adolescents with their rearing parents. Main Exposure The main exposure was adoptive status: nonadopted (n = 540), international adoptive placement (n = 514), or domestic adoptive placement (n = 178). OUTCOME MEASURES: Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) clinical assessments based on child and parent reports of attention-deficit/hyperactivity, oppositional defiant, conduct, major depressive, and separation anxiety disorders; teacher reports of psychological health; and contact with mental health professionals. RESULTS: Adoptees scored only moderately higher than nonadoptees on quantitative measures of mental health. Nevertheless, being adopted approximately doubled the odds of having contact with a mental health professional (odds ratio [OR], 2.05; 95% confidence interval [CI], 1.48-2.84) and of having a disruptive behavior disorder (OR, 2.34; 95% CI, 1.72-3.19). Relative to international adoptees, domestic adoptees had higher odds of having an externalizing disorder (OR, 2.60; 95% CI, 1.67-4.04). CONCLUSIONS: Moderate mean differences in quantitative indicators of mental health can lead to substantial differences in disorder prevalence. Although most adopted adolescents are psychologically healthy, they may be at elevated risk for some externalizing disorders, especially among those domestically placed.

How useful are voluntary medication error reports? The case of warfarin-related medication errors.

BACKGROUND: A study was conducted to explore the value and limitations of voluntary medical error reports and to learn about common errors in warfarin use. METHODS: Voluntary reports of 8,837 inpatient errors and 820 outpatient errors in warfarin use submitted by 445 hospitals and 192 outpatient facilities participating in MEDMARX, a voluntary medication error reporting system, from 2002 to 2004, were gathered. RESULTS: Overall, errors occurred most often during transcription/documentation (35%) and administration (30%) in hospitals, and during prescribing (31%) and dispensing (39%) in outpatient settings. Dosing errors were the most common type. In hospitals, more than 50% of reported errors were initiated by nurses, and 50% were intercepted by nurses, whereas in outpatient settings, about 50% of reported errors occurred in pharmacies and 50% were intercepted by pharmacists. About 17% of inpatient and 13% of outpatient warfarin errors resulted in changes in patient care, and 42% of inpatient and 62% of outpatient errors resulted in procedural changes. Cascade analysis and textual descriptions further located specific, correctible safety lapses. DISCUSSION: Voluntary medical error reporting systems can, to some extent, provide meaningful and actionable information to guide patient safety improvement, but their usefulness is limited because of a lack of details, incomplete reporting, underreporting, and various reporting biases.

Early onset problem behavior, young adult psychopathology, and contextual risk.

A prospective study of 692 male twins was undertaken to investigate the relationships among early adolescent problem behavior, contextual risk, and disinhibitory psychopathology. Early adolescent problem behavior was assessed by the number of the following behaviors engaged in by the time of the age-14 assessment: (1) tobacco use, (2) alcohol use, (3) marijuana use, (4) other illicit drug use, (5) sexual intercourse, and (6) police contact. Contextual risk was assessed as a composite of measures of peer models, parent-offspring conflict, and academic engagement from the age-14 assessment. Disinhibitory psychopathology was assessed by symptoms of nicotine dependence, alcohol dependence, drug dependence, and adult antisocial behavior at the age-18 assessment. Early adolescent problem behavior and contextual risk were strongly correlated (r = .53) and both were strongly and independently associated with symptoms of disinhibitory psychopathology (r from .35 to .60). The association of early adolescent problem behavior with both contextual risk and disinhibitory psychopathology was mediated entirely by genetic factors while the association between contextual risk and disinhibitory psychopathology was mediated by both genetic and nonshared environmental factors. The results are discussed in the context of emerging research on the prognostic significance of early adolescent problem behavior for risk of adult psychopathology.

Potential benefits and problems with computerized prescriber order entry: analysis of a voluntary medication error-reporting database.

PURPOSE: The potential benefits and problems associated with computerized prescriber-order-entry (CPOE) systems were studied. METHODS: A national voluntary medication error-reporting database, Medmarx, was used to compare facilities that had CPOE with those that did not have CPOE. The characteristics of medication errors reportedly caused by CPOE were explored, and the text descriptions of these errors were qualitatively analyzed. RESULTS: Facilities with CPOE reported fewer inpatient medication errors and more outpatient medication errors than facilities without CPOE, but the statistical significance of these differences could not be determined. Facilities with CPOE less frequently reported medication errors that reached patients (p < 0.01) or harmed patients (p < 0.01). More than 7000 CPOE-related medication errors were reported over seven months in 2003, and about 0.1% of them resulted in harm or adverse events. The most common CPOE errors were dosing errors (i.e., wrong dose, wrong dosage form, or extra dose). Both quantitative and qualitative analyses indicate that CPOE could lead to medication errors not only because of faulty computer interface, mis-communication with other systems, and lack of adequate decision support but also because of common human errors such as knowledge deficit, distractions, inexperience, and typing errors. CONCLUSION: A national, voluntary medication error-reporting database cannot be used to determine the effectiveness of a CPOE system in reducing medication errors because of the variability in the number of reports from different institutions. However, it may provide valuable information on the specific types of errors related to CPOE systems.

Technology and patient safety: a two-edged sword.

The Agency for Healthcare Research and Quality (AHRQ) is now the world's largest funder of patient safety research. Part of AHRQ's research focus is to examine evidence to help determine which technologies can be used to effectively minimize harm and improve patient safety. The report of the Institute of Medicine (IOM). To Err is Human stressed the importance of automating repetitive, time-consuming, and error-prone tasks through the use of technology. While automation holds substantial promise for improved safety, error experts caution that all technology introduces the potential for new and different errors. It is critical that any new automated system be tested in actual operational settings to determine what, if any, unanticipated failures exist. Field-based research is essential in the emerging field of patient safety to create the evidence as to which technologies actually improve patient safety and those that may well increase the potential for harm.