Susan E. Young

Individual Differences in Executive Functions Are Almost Entirely Genetic in Origin

Recent psychological and neuropsychological research suggests that executive functions--the cognitive control processes that regulate thought and action--are multifaceted and that different types of executive functions are correlated but separable. The present multivariate twin study of 3 executive functions (inhibiting dominant responses, updating working memory representations, and shifting between task sets), measured as latent variables, examined why people vary in these executive control abilities and why these abilities are correlated but separable from a behavioral genetic perspective. Results indicated that executive functions are correlated because they are influenced by a highly heritable (99%) common factor that goes beyond general intelligence or perceptual speed, and they are separable because of additional genetic influences unique to particular executive functions. This combination of general and specific genetic influences places executive functions among the most heritable psychological traits. These results highlight the potential of genetic approaches for uncovering the biological underpinnings of executive functions and suggest a need for examining multiple types of executive functions to distinguish different levels of genetic influences.

Not All Executive Functions Are Related to Intelligence

Accumulating evidence suggests that executive functions (EFs) are related to intelligence, despite neuropsychological results initially considered evidence of no such relation. However, findings that EFs are not unitary raise the issue of how intelligence relates to different EFs. This study examined the relations of fluid and crystallized intelligence and Wechsler Adult Intelligence Scale IQ to three separable EFs—inhibiting prepotent responses (inhibiting), shifting mental sets (shifting), and updating working memory (updating)—in young adults. Updating was highly correlated with the intelligence measures, but inhibiting and shifting were not. Furthermore, in structural equation models controlling for the inter-EF correlations, updating remained strongly related to intelligence, but the relations of inhibiting and shifting to intelligence were small and not significant. The results indicate that intelligence measures differentially relate to these three EFs, suggesting that current intelligence measures do not equally assess a wide range of executive control abilities likely required for many “intelligent” behaviors.

Genetic and environmental influences on behavioral disinhibition.

Comorbidity among childhood disruptive behavioral disorders is commonly reported in both epidemiologic and clinical studies. These problems are also associated with early substance use and other markers of behavioral disinhibition. Previous twin research has suggested that much of the covariation between antisocial behavior and alcohol dependence is due to common genetic influences. Similar results have been reported for conduct problems and hyperactivity. For the present study, an adolescent sample consisting of 172 MZ and 162 DZ twin pairs, recruited through the Colorado Twin Registry and the Colorado Longitudinal Twin Study were assessed using standardized psychiatric interviews and personality assessments. DSM-IV symptom counts for conduct disorder and attention deficit hyperactivity disorder, along with a measure of substance experimentation and novelty seeking, were used as indices of a latent behavioral disinhibition trait. A confirmatory factor model fit to individual-level data showed a strong common factor accounting for 16-42% of the observed variance in each measure. A common pathway model evaluating the genetic and environmental architecture of the latent phenotype suggested that behavioral disinhibition is highly heritable (a(2) = 0.84), and is not influenced significantly by shared environmental factors. A residual correlation between conduct disorder and substance experimentation was explained by shared environmental effects, and a residual correlation between attention deficit hyperactivity disorder and novelty seeking was accounted for by genetic dominance. These results suggest that a variety of adolescent problem behaviors may share a common underlying genetic risk.

Substance use, abuse and dependence in adolescence: prevalence, symptom profiles and correlates

We present data on the lifetime prevalence of substance use, abuse and dependence in adolescents obtained through structured psychiatric interviews and self-report questionnaires. Most notably, we evaluate symptom profiles based on DSM-IV abuse and dependence criteria for tobacco, alcohol and marijuana, including a gender comparison. Participants are 3,072 adolescents (12-18 years) drawn from three community-based family samples in Colorado. Age trends suggest that substance use is a developmental phenomenon, which increases almost linearly from early to late adolescence. Substance use disorders are less common than experimentation in adolescence, but approximately 1 in 4 adolescents in the oldest cohorts meets criteria for abuse for at least one substance, and 1 in 5 meets criteria for substance dependence. By age 18 nearly 1 in 3 adolescents report daily smoking and 8.6% meet criteria for tobacco dependence. Although alcohol is the most commonly abused substance (10%), a slightly larger proportion of adolescents meet criteria for dependence on marijuana (4.3%) than alcohol (3.5%). Gender differences in prevalence of use more often show greater use in males than females. Males more frequently meet criteria for dependence on alcohol and marijuana in late adolescence, while females are more often nicotine dependent. A comparison of abuse and dependence symptom profiles shows some interesting variability across substances, and suggests that manifestations of a subset of symptoms are gender specific.

Behavioral disinhibition: liability for externalizing spectrum disorders and its genetic and environmental relation to response inhibition across adolescence.

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.

Depression in Substance-Dependent Delinquents

OBJECTIVE Depression often is comorbid with conduct disorder. The purpose of this study is to assess whether, among youths with conduct disorder, those with depression differ in other ways from those without depression. METHOD Ninety-nine delinquent boys (aged 13 through 19 years) were evaluated with the Diagnostic Interview Schedule for Children and other instruments. All boys had conduct disorder and substance use disorders. RESULTS Staff-rated and self-rated depression scores correlated significantly. Twenty-one boys had major depression and/or dysthymia. Depressed boys had more substance dependence diagnoses and were more likely to have attention-deficit hyperactivity disorder, posttraumatic stress disorder, and anxiety disorders, compared with the nondepressed boys. Depressed boys tended to develop conduct symptoms earlier than did the nondepressed boys. Depression scores did not change after at least 4 weeks of abstinence, for either depressed or nondepressed boys. CONCLUSIONS Depressed delinquents have more substance dependence diagnoses, tend to initiate behavioral problems at an earlier age, have increased anxiety and attentional problems, and more trauma effects, than nondepressed delinquents. Depression does not appear to be related to substance intoxication, since it is not alleviated after 4 weeks of abstinence. Such boys may require combined psychiatric and substance treatment.

Developmental epidemiology of drug use and abuse in adolescence and young adulthood: Evidence of generalized risk

Past studies highlight a narrowing gender gap and the existence of a shared etiology across substances of abuse; however, few have tested developmental models using longitudinal data. We present data on developmental trends of alcohol, tobacco, and marijuana use, abuse and dependence assessed during adolescence and young adulthood in a community-based Colorado twin sample of 1733 respondents through self-report questionnaires and structured psychiatric interviews. Additionally, we report on the rates of multiple substance use and disorders at each developmental stage, and the likelihood of a substance use disorder (SUD; i.e., abuse or dependence) diagnosis in young adulthood based on adolescent drug involvement. Most notably, we evaluate whether the pattern of multiple substance use and disorders and likelihood ratios across substances support a model of generalized risk. Lastly, we evaluate whether the ranked magnitudes of substance-specific risk match the addiction liability ranking. Substance use and SUDs are developmental phenomena, which increase from adolescence to young adulthood with few and inconsistent gender differences. Adolescents and young adults are not specialized users, but rather tend to use or abuse multiple substances increasingly with age. Risk analyses indicated that progression toward a SUD for any substance was increased with prior involvement with any of the three substances during adolescence. Despite the high prevalence of alcohol use, tobacco posed the greatest substance-specific risk for developing subsequent problems. Our data also confirm either a generalized risk or correlated risk factors for early onset substance use and subsequent development of SUDs.

Childhood Maltreatment, Subsequent Antisocial Behavior, and the Role of Monoamine Oxidase A Genotype

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.

Greater Attention Problems During Childhood Predict Poorer Executive Functioning in Late Adolescence

Attention problems (behavior problems including inattention, disorganization, impulsivity, and hyperactivity) are widely thought to reflect deficits in executive functions (EFs). However, it is unclear whether attention problems differentially relate to distinct EFs and how developmental stability and change predict levels of EFs in late adolescence. We investigated, in an unselected sample, how teacher-rated attention problems from ages 7 to 14 years related to three correlated but separable EFs, measured as latent variables at age 17. Attention problems at all ages significantly predicted later levels of response inhibition and working memory updating, and to some extent set shifting; the relation to inhibiting was stronger than the relations to the other EFs or IQ. Growth models indicated that attention problems were quite stable in this age range, and it was the initial levels of problems, rather than their changes across time, that predicted later EFs. These results support the hypothesis that attention problems primarily reflect difficulties with response inhibition.

Interaction between MAO-A genotype and maltreatment in the risk for conduct disorder: failure to confirm in adolescent patients.

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.