Joshua D. Isen

Impact of adolescent marijuana use on intelligence : Results from two longitudinal twin studies

Significance Marijuana is the most commonly used recreational drug in the United States. Some studies suggest that marijuana use in adolescence is linked to declines in intellectual functioning. Because of the infeasibility of studying this phenomenon experimentally, it is unclear whether the association can be causally attributed to marijuana use itself or is instead the result of confounding factors. We approach this issue quasiexperimentally using longitudinal samples of adolescent twins. Among twin pairs discordant for marijuana use, we assessed intelligence quotient (IQ) score changes while adjusting for the effects of genetic influences and other factors shared by members of the same twin pair. Results suggest that familial confounds underlie the association between adolescent marijuana use and declining IQ scores. Marijuana is one of the most commonly used drugs in the United States, and use during adolescence—when the brain is still developing—has been proposed as a cause of poorer neurocognitive outcome. Nonetheless, research on this topic is scarce and often shows conflicting results, with some studies showing detrimental effects of marijuana use on cognitive functioning and others showing no significant long-term effects. The purpose of the present study was to examine the associations of marijuana use with changes in intellectual performance in two longitudinal studies of adolescent twins (n = 789 and n = 2,277). We used a quasiexperimental approach to adjust for participants’ family background characteristics and genetic propensities, helping us to assess the causal nature of any potential associations. Standardized measures of intelligence were administered at ages 9–12 y, before marijuana involvement, and again at ages 17–20 y. Marijuana use was self-reported at the time of each cognitive assessment as well as during the intervening period. Marijuana users had lower test scores relative to nonusers and showed a significant decline in crystallized intelligence between preadolescence and late adolescence. However, there was no evidence of a dose–response relationship between frequency of use and intelligence quotient (IQ) change. Furthermore, marijuana-using twins failed to show significantly greater IQ decline relative to their abstinent siblings. Evidence from these two samples suggests that observed declines in measured IQ may not be a direct result of marijuana exposure but rather attributable to familial factors that underlie both marijuana initiation and low intellectual attainment.

A meta-analytic assessment of Wechsler's P>V sign in antisocial populations

The dichotomy between Verbal IQ and Performance IQ was a hallmark of the Wechsler scales for over 60 years. Wechsler noted that adolescent delinquents tend to score higher on the Performance tests than the Verbal tests (P>V). A plethora of studies have examined the clinical utility of the P>V sign in juvenile delinquents. However, there have been few attempts to systematically quantify the size of this discrepancy in antisocial children and adults. A meta-analysis of 131 studies was conducted to examine whether the PIQ-VIQ discrepancy is found across different age groups as well as sex, race, and test instrument. Results indicated that the discrepancy is characteristic of antisocial females as well as males. The discrepancy is largest in adolescents (6 points), smaller in adults (3 points), and negligible in young children. Furthermore, the effect is moderated by race and instrument, such that the PIQ-VIQ discrepancy is smallest for African-Americans and for subjects administered the Wechsler Adult Intelligence Scale. Among adolescents administered the Wechsler Intelligence Scale for Children, the poorest subtests are Vocabulary and Information. It is argued that delinquency is intertwined with school failure, and that verbal-educational deficits accumulate over the course of childhood, eventually manifesting as P>V.

Sex-specific association between psychopathic traits and electrodermal reactivity in children.

This study investigated the relationship of skin conductance response (SCR) to a child psychopathy measure. Blunted electrodermal activity is a theoretically important characteristic of psychopathy, but it has not been fully explored in preadolescents or females. The authors tested the hypothesis that reduced SCR magnitude is associated with psychopathic-like traits in boys and girls. Participants were drawn from an ethnically diverse community sample of 9- to 10-year-old twins. Given the fact that members of each twin pair were rated by the same individual (i.e., their caregiver) on the Child Psychopathy Scale, the authors examined individual differences at the within-family level. Skin conductance data were collected during a passive auditory task consisting of 75-dB tones as well as miscellaneous sounds (e.g., baby cries, bird noises, and speech-like stimuli). Reduced SCR magnitude (hyporeactivity) was characteristic only of boys with higher psychopathy scores. More specifically, electrodermal hyporeactivity was linked to the interpersonal facet of psychopathy, suggesting that it is a biological marker of a manipulative and deceitful orientation in males. No association was found between SCRs and psychopathic traits in girls, indicating the importance of sex specific etiologies of psychopathy in childhood.

Genome-wide association study of lifetime cannabis use based on a large meta-analytic sample of 32 330 subjects from the International Cannabis Consortium

Cannabis is the most widely produced and consumed illicit psychoactive substance worldwide. Occasional cannabis use can progress to frequent use, abuse and dependence with all known adverse physical, psychological and social consequences. Individual differences in cannabis initiation are heritable (40–48%). The International Cannabis Consortium was established with the aim to identify genetic risk variants of cannabis use. We conducted a meta-analysis of genome-wide association data of 13 cohorts (N=32 330) and four replication samples (N=5627). In addition, we performed a gene-based test of association, estimated single-nucleotide polymorphism (SNP)-based heritability and explored the genetic correlation between lifetime cannabis use and cigarette use using LD score regression. No individual SNPs reached genome-wide significance. Nonetheless, gene-based tests identified four genes significantly associated with lifetime cannabis use: NCAM1, CADM2, SCOC and KCNT2. Previous studies reported associations of NCAM1 with cigarette smoking and other substance use, and those of CADM2 with body mass index, processing speed and autism disorders, which are phenotypes previously reported to be associated with cannabis use. Furthermore, we showed that, combined across the genome, all common SNPs explained 13–20% (P<0.001) of the liability of lifetime cannabis use. Finally, there was a strong genetic correlation (rg=0.83; P=1.85 × 10−8) between lifetime cannabis use and lifetime cigarette smoking implying that the SNP effect sizes of the two traits are highly correlated. This is the largest meta-analysis of cannabis GWA studies to date, revealing important new insights into the genetic pathways of lifetime cannabis use. Future functional studies should explore the impact of the identified genes on the biological mechanisms of cannabis use.

Genetic and Environmental Influences on the Junior Temperament and Character Inventory in a Preadolescent Twin Sample

This study evaluated the genetic and environmental structure of personality variables from the Junior Temperament and Character Inventory (JTCI), in 605 pairs of 9- and 10-year old twins. There is a paucity of information on the biometric structure of temperament and character traits in preadolescent children. Latent factor models were fit to the subscales/items of each trait as a method of estimating genetic and environmental effects on true score variance, especially since internal consistency and reliability were moderate or low for some scales (particularly Reward Dependence and Persistence). Shared environmental influences on Cooperativeness were substantial. Significant heritability estimates were obtained for Self-directedness and Harm Avoidance, but not Novelty Seeking, Reward Dependence or Persistence. With the exception of Harm Avoidance, each of the scales failed to show measurement invariance with respect to sex, suggesting these scales may differ in meaning for boys and girls at this age.

The genetic and environmental etiology of sympathetic and parasympathetic activity in children

The present study examines the genetic and environmental etiology of the associations among respiratory sinus arrhythmia (RSA), heart rate (HR), skin conductance level (SCL), and non-specific skin conductance responses (NS-SCR)—measures that purportedly index the parasympathetic and sympathetic branches of the autonomic nervous system. The sample was drawn from a cohort of 1,219 preadolescent twins (aged 9–10). Multivariate analyses of the data were conducted using structural equation modeling. Almost all genetic and environmental influences on the measures acted through two latent factors. The first latent factor was largely responsible for the variance in heart rate, SCL and NS-SCR, reflecting sympathetic activity, and its proportions of variance due to genetic and shared environmental influences were 27 and 28% in males, and 31 and 41% in females, respectively. The second latent factor accounted for the variance in RSA and heart rate, reflecting parasympathetic activity; genetic and shared environmental factors explained 27 and 23% of the variance in males, respectively, and 35 and 18% of the variance in females. Measurement-specific genetic effects accounted for 14–27% of the total variance in RSA and SCL, and measurement-specific shared environmental effects accounted for 10–12% in SCL. In general, the validity of separate sympathetic and parasympathetic constructs was supported.

The heritability of the skin conductance orienting response: a longitudinal twin study.

The orienting response is a widely used experimental paradigm that reflects the association between electrodermal activity and psychological processes. The present study examined the genetic and environmental etiology of skin conductance orienting response (SCOR) magnitude in a sample of twins assessed at ages 9-10, 11-13 and 14-16 years. Structural equation modeling at each visit showed that genetic influences explained 56%, 83%, and 48% of the total variance in SCOR at visits 1, 2, and 3, respectively, with the remaining variance explained by non-shared environmental factors. SCOR was moderately stable across ages, with phenotypic correlations between time points ranging from .35 to .45. A common genetic factor explained 36%, 45% and 49% of the variance in SCOR magnitude across development. Additional age-specific genetic effects were found at ages 9-10 and 11-13 years, explaining 18% and 35% of the variance, respectively. The genetic correlations among the three time points were high, ranging from .55 to .73, indicating a substantial continuity in genetic influences from ages 9 to 16. These findings suggest that genetic factors are important influences in SCOR magnitude during late childhood and adolescence.

Heritability and molecular genetic basis of electrodermal activity: a genome-wide association study.

The molecular genetic basis of electrodermal activity (EDA) was analyzed using 527,829 single nucleotide polymorphisms (SNPs) in a large population-representative sample of twins and parents (N = 4,424) in relation to various EDA indices. Biometric analyses suggested that approximately 50% or more of variance in all EDA indices was heritable. The combined effect of all SNPs together accounted for a significant amount of variance in each index, affirming their polygenic basis and heritability. However, none of the SNPs were genome-wide significant for any EDA index. Previously reported SNP associations with disorders such as substance dependence or schizophrenia, which have been linked to EDA abnormalities, were not significant; nor were associations between EDA and genes in specific neurotransmitter systems. These results suggest that EDA is influenced by multiple genes rather than by polymorphisms with large effects.

Aggressive-Antisocial Boys Develop Into Physically Strong Young Men

Young men with superior upper-body strength typically show a greater proclivity for physical aggression than their weaker male counterparts. The traditional interpretation of this phenomenon is that young men calibrate their attitudes and behaviors to their physical formidability. Physical strength is thus viewed as a causal antecedent of aggressive behavior. The present study is the first to examine this phenomenon within a developmental framework. We capitalized on the fact that physical strength is a male secondary sex characteristic. In two longitudinal cohorts of children, we estimated adolescent change in upper-body strength using the slope parameter from a latent growth model. We found that males’ antisocial tendencies temporally precede their physical formidability. Boys, but not girls, with greater antisocial tendencies in childhood attained larger increases in physical strength between the ages of 11 and 17. These results support sexual selection theory, indicating an adaptive congruence between male-typical behavioral dispositions and subsequent physical masculinization during puberty.

Heritability and molecular genetic basis of electrodermal activity

The molecular genetic basis of electrodermal activity (EDA) was analyzed using 527,829 single nucleotide polymorphisms (SNPs) in a large population-representative sample of twins and parents (N = 4,424) in relation to various EDA indices. Biometric analyses suggested that approximately 50% or more of variance in all EDA indices was heritable. The combined effect of all SNPs together accounted for a significant amount of variance in each index, affirming their polygenic basis and heritability. However, none of the SNPs were genome-wide significant for any EDA index. Previously reported SNP associations with disorders such as substance dependence or schizophrenia, which have been linked to EDA abnormalities, were not significant; nor were associations between EDA and genes in specific neurotransmitter systems. These results suggest that EDA is influenced by multiple genes rather than by polymorphisms with large effects.