Robin P. Corley

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.

The heritability of general cognitive ability increases linearly from childhood to young adulthood

Although common sense suggests that environmental influences increasingly account for individual differences in behavior as experiences accumulate during the course of life, this hypothesis has not previously been tested, in part because of the large sample sizes needed for an adequately powered analysis. Here we show for general cognitive ability that, to the contrary, genetic influence increases with age. The heritability of general cognitive ability increases significantly and linearly from 41% in childhood (9 years) to 55% in adolescence (12 years) and to 66% in young adulthood (17 years) in a sample of 11 000 pairs of twins from four countries, a larger sample than all previous studies combined. In addition to its far-reaching implications for neuroscience and molecular genetics, this finding suggests new ways of thinking about the interface between nature and nurture during the school years. Why, despite lifes ‘slings and arrows of outrageous fortune’, do genetically driven differences increasingly account for differences in general cognitive ability? We suggest that the answer lies with genotype–environment correlation: as children grow up, they increasingly select, modify and even create their own experiences in part based on their genetic propensities.

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.

The Heritability of Inhibited and Uninhibited Behavior: A Twin Study.

Young children who respond to the unfamiliar with wariness and avoidance belong to a temperamental category called behaviorally inhibited; sociable children who approach the unfamiliar are called uninhibited. This study assessed the heritable nature of these 2 categories. The longitudinal sample consisted of 178 same-sex twin pairs seen at 14 months and 162 pairs seen at 20 and 24 months. An aggregate inhibition index was constructed at each of the 3 ages by averaging standard scores for observed laboratory behaviors indicative of wariness

Temperament, Emotion, and Cognition at Fourteen Months: The MacArthur Longitudinal Twin Study

200 pairs of twins were assessed at 14 months of age in the laboratory and home. Measures were obtained of temperament, emotion, and cognition/language. Comparisons between identical and fraternal twin correlations suggest that individual differences are due in part to heritable influences. For temperament, genetic influence was significant for behavioral observations of inhibition to the unfamiliar, tester ratings of activity, and parental ratings of temperament. For emotion, significant genetic influence was found for empathy and parental ratings of negative emotion. The estimate of heritability for parental report of expression of negative emotions was relatively high, whereas that for expression of positive emotions was low, a finding consistent with previous research. For cognition and language, genetic influence was significant for behavioral indices of spatial memory, categorization, and word comprehension. Shared rearing environment appears influential for parental reports of language and for positive emotions, but not for other measures of emotion or for temperament.

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.

The CHRNA5/A3/B4 Gene Cluster Variability as an Important Determinant of Early Alcohol and Tobacco Initiation in Young Adults

BACKGROUND One potential site of convergence of the nicotine and alcohol actions is the family of the neuronal nicotinic acetylcholine receptors. Our study examines the genetic association between variations in the genomic region containing the CHRNA5, A3, and B4 gene cluster (A5A3B4) and several phenotypes of alcohol and tobacco use in an ethnically diverse young adult sample. Significant results were then replicated in a separate adult population-representative sample. METHODS In a selected sample, nine single nucleotide polymorphisms (SNPs) were tested for association with various nicotine and alcohol phenotypes, including age of initiation and measures of frequency, quantity, and subjective responses to the substances. Analysis was conducted with the statistical genetics program WHAP in the full sample (1075 subjects) including ethnicities as covariates and within each ethnic group sub-sample. Replication of the significant results in a separate population-based sample was carried out with the PBAT statistical genetics program. RESULTS Two linked SNPs (rs8023462 and rs1948) located in a conserved region of the A5A3B4 gene cluster significantly predicted early age of initiation for tobacco with a hazard ratio (HR) of 1.35 (95% confidence interval [CI]1.08-1.70) for the CC genotype of rs8023462 and a HR of 1.29 (95% CI 1.01-1.63) for the TT genotype of rs1948 [corrected]. These findings were then replicated in a separate population-representative sample, showing rs1948 and rs8023462 to be associated with age of initiation for both tobacco and alcohol use (p < .01 and p < .001). CONCLUSIONS Variations in A5A3B4 genes might influence behaviors that promote early age of experimentation with drugs.