Associations between adolescent cannabis use and neuropsychological decline: a longitudinal co-twin control study.
ABSTRACT: AIMS:This study tested whether adolescents who used cannabis or met criteria for cannabis dependence showed neuropsychological impairment prior to cannabis initiation and neuropsychological decline from before to after cannabis initiation. DESIGN:A longitudinal co-twin control study. SETTING AND PARTICIPANTS:Participants were 1989 twins from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative birth cohort of twins born in England and Wales from 1994 to 1995. MEASUREMENTS:Frequency of cannabis use and cannabis dependence were assessed at age 18. Intelligence quotient (IQ) was obtained at ages 5, 12 and 18. Executive functions were assessed at age 18. FINDINGS:Compared with adolescents who did not use cannabis, adolescents who used cannabis had lower IQ in childhood prior to cannabis initiation and lower IQ at age 18, but there was little evidence that cannabis use was associated with IQ decline from ages 12-18. For example, adolescents with cannabis dependence had age 12 and age 18 IQ scores that were 5.61 (t = -3.11, P = 0.002) and 7.34 IQ points (t = -5.27, P < 0.001) lower than adolescents without cannabis dependence, but adolescents with cannabis dependence did not show greater IQ decline from age 12-18 (t = -1.27, P = 0.20). Moreover, adolescents who used cannabis had poorer executive functions at age 18 than adolescents who did not use cannabis, but these associations were generally not apparent within twin pairs. For example, twins who used cannabis more frequently than their co-twin performed similarly to their co-twin on five of six executive function tests (Ps > 0.10). The one exception was that twins who used cannabis more frequently than their co-twin performed worse on one working memory test (Spatial Span reversed; ? = -0.07, P = 0.036). CONCLUSIONS:Short-term cannabis use in adolescence does not appear to cause IQ decline or impair executive functions, even when cannabis use reaches the level of dependence. Family background factors explain why adolescent cannabis users perform worse on IQ and executive function tests.
Project description:BACKGROUND AND AIMS:Cannabis is one of the most commonly used substances among adolescents and young adults. Earlier age at cannabis initiation is linked to adverse life outcomes, including multi-substance use and dependence. This study estimated the heritability of age at first cannabis use and identified associations with genetic variants. METHODS:A twin-based heritability analysis using 8055 twins from three cohorts was performed. We then carried out a genome-wide association meta-analysis of age at first cannabis use in a discovery sample of 24?953 individuals from nine European, North American and Australian cohorts, and a replication sample of 3735 individuals. RESULTS:The twin-based heritability for age at first cannabis use was 38% [95% confidence interval (CI) = 19-60%]. Shared and unique environmental factors explained 39% (95% CI = 20-56%) and 22% (95% CI = 16-29%). The genome-wide association meta-analysis identified five single nucleotide polymorphisms (SNPs) on chromosome 16 within the calcium-transporting ATPase gene (ATP2C2) at P < 5E-08. All five SNPs are in high linkage disequilibrium (LD) (r2 > 0.8), with the strongest association at the intronic variant rs1574587 (P = 4.09E-09). Gene-based tests of association identified the ATP2C2 gene on 16q24.1 (P = 1.33e-06). Although the five SNPs and ATP2C2 did not replicate, ATP2C2 has been associated with cocaine dependence in a previous study. ATP2B2, which is a member of the same calcium signalling pathway, has been associated previously with opioid dependence. SNP-based heritability for age at first cannabis use was non-significant. CONCLUSION:Age at cannabis initiation appears to be moderately heritable in western countries, and individual differences in onset can be explained by separate but correlated genetic liabilities. The significant association between age of initiation and ATP2C2 is consistent with the role of calcium signalling mechanisms in substance use disorders.
Project description:The active component of cannabis, delta-9 tetrahydrocannabinol (THC), has a long half-life and widespread neurocognitive effects. There are inconsistent reports of neurocognitive deficits in adults and adolescents with cannabis use disorders (CUD), particularly after a period of abstinence.This study aims to examine neurocognitive measures (IQ, academic achievement, attention, memory, executive functions) in abstinent adolescents with CUD, while controlling for demographic, psychopathology, and poly-substance confounders.We investigated neurocognitive performance in three groups: adolescents with CUD after successful first treatment and in full remission (n?=?33); controls with psychiatric disorders without substance use disorder history (n?=?37); and healthy adolescents (n?=?43).Adolescents with psychiatric disorders, regardless of CUD status, performed significantly worse than the healthy adolescents in academic achievement. No group differences were seen in IQ, attention, memory, or executive functions. Lower academic achievement was positively associated with younger age of CUD onset, regular cannabis use, and maximum daily use. In the CUD group, lifetime nicotine use episodes were negatively associated with IQ. Lower overall neurocognitive function was associated with younger age of onset of regular cannabis use and relapse within the 1 year follow-up.Verifiably, abstinent adolescents with CUD history did not differ from the two comparison groups, suggesting that previously reported neurocognitive deficits may be related to other factors, including residual drug effects, preexisting cognitive deficits, concurrent use of other substances (e.g., nicotine), or psychopathology. Adolescents with CUD may not be vulnerable to THC neuropsychological deficits once they achieve remission from all drugs for at least 30 days.
Project description:In this report, we present the first regional quantitative analysis of age-related differences in the heritability of cortical thickness using anatomic MRI with a large pediatric sample of twins, twin siblings, and singletons (n = 600, mean age 11.1 years, range 5-19). Regions of primary sensory and motor cortex, which develop earlier, both phylogenetically and ontologically, show relatively greater genetic effects earlier in childhood. Later developing regions within the dorsal prefrontal cortex and temporal lobes conversely show increasingly prominent genetic effects with maturation. The observation that regions associated with complex cognitive processes such as language, tool use, and executive function are more heritable in adolescents than children is consistent with previous studies showing that IQ becomes increasingly heritable with maturity(Plomin et al. 1997: Psychol Sci 8:442-447). These results suggest that both the specific cortical region and the age of the population should be taken into account when using cortical thickness as an intermediate phenotype to link genes, environment, and behavior.
Project description:OBJECTIVE:Self-harm is associated with violent offending. However, little is known about young people who engage in "dual-harm" behavior. The authors investigated antecedents, clinical features, and life characteristics distinguishing dual-harming adolescents from those who self-harm only. METHODS:Participants were from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative U.K. cohort of 2,232 twins born in 1994 and 1995. Self-harm in adolescence was assessed through interviews at age 18. Violent offending was assessed using a computer questionnaire at age 18 and police records through age 22. Risk factors were assessed between ages 5 and 12. Adolescent mental health, victimization, personality functioning, and use of support services were measured at age 18. RESULTS:Self-harm was associated with violent crime (odds ratio=3.50, 95% CI=2.61-4.70), even after accounting for familial risk factors. Dual harmers had been victims of violence from childhood and exhibited lower childhood self-control and lower childhood IQ than self-only harmers. Dual harmers experienced higher rates of concurrent psychotic symptoms and substance dependence. They also exhibited distinct personality styles characterized by resistance to change and by emotional and interpersonal lability. However, dual harmers were not more likely than self-only harmers to have contact with mental health services. CONCLUSIONS:Dual harmers have self-control difficulties and are immersed in violence from a young age. A treatment- rather than punishment-oriented approach is indicated to meet these individuals' needs. Connecting self-harming adolescents with delinquency-reduction programs and transdiagnostic approaches that target self-regulation may reduce harmful behaviors. Preventing childhood maltreatment and implementing strategies to reduce victimization exposure could mitigate risk for both internalized and externalized violence.
Project description:Recent reports show that fewer adolescents believe that regular cannabis use is harmful to health. Concomitantly, adolescents are initiating cannabis use at younger ages, and more adolescents are using cannabis on a daily basis. The purpose of the present study was to test the association between persistent cannabis use and neuropsychological decline and determine whether decline is concentrated among adolescent-onset cannabis users. Participants were members of the Dunedin Study, a prospective study of a birth cohort of 1,037 individuals followed from birth (1972/1973) to age 38 y. Cannabis use was ascertained in interviews at ages 18, 21, 26, 32, and 38 y. Neuropsychological testing was conducted at age 13 y, before initiation of cannabis use, and again at age 38 y, after a pattern of persistent cannabis use had developed. Persistent cannabis use was associated with neuropsychological decline broadly across domains of functioning, even after controlling for years of education. Informants also reported noticing more cognitive problems for persistent cannabis users. Impairment was concentrated among adolescent-onset cannabis users, with more persistent use associated with greater decline. Further, cessation of cannabis use did not fully restore neuropsychological functioning among adolescent-onset cannabis users. Findings are suggestive of a neurotoxic effect of cannabis on the adolescent brain and highlight the importance of prevention and policy efforts targeting adolescents.
Project description:OBJECTIVE:Cannabis use, particularly at an early age, has been linked to suicidal thoughts and behavior, but minimal work has examined the association between cannabis use and lifetime nonsuicidal self-injury (NSSI). The current study aims to characterize the overlap between lifetime and early cannabis use and NSSI and to examine genetic and environmental mechanisms of this association. METHOD:Adult male and female twins from the Australian Twin Registry (N = 9,583) were used to examine the odds of NSSI associated with lifetime cannabis use and early cannabis use (i.e., <17 years of age). These associations were also examined within monozygotic (MZ) twins discordant for cannabis use and MZ twins discordant for early cannabis use. Analyses were replicated in an independent sample of female twins (n = 3,787) accounting for the age at onset of cannabis use and NSSI. RESULTS:Lifetime cannabis use (odds ratio [OR] = 2.84, 95% CI [2.23, 3.61]) and early cannabis use were associated with increased odds of NSSI (OR = 2.15, 95% CI [1.75, 2.65]), and this association remained when accounting for covariates. The association was only significant, however, in MZ twin pairs discordant for early cannabis use (OR = 3.20, 95% CI [1.17, 8.73]). Replication analyses accounting for the temporal ordering of cannabis use and NSSI yielded similar findings of nominal significance. CONCLUSIONS:Results suggest that NSSI is associated with cannabis involvement via differing mechanisms. For lifetime cannabis use, the lack of association in discordant pairs suggests the role of shared genes and family environment. However, in addition to such shared familial influences, person-specific and putatively causal factors contribute to the relationship between early cannabis use and NSSI. Therefore, delaying the onset of cannabis use may reduce exposure to influences that exacerbate vulnerabilities to NSSI.
Project description:BACKGROUND AND AIMS:Individual differences in DSM-IV personality disorders (PDs) are associated with increased prevalence of substance use disorders. Our aims were to determine which combination of PDs trait scores best predict cannabis use (CU) and cannabis use disorder (CUD), and to estimate the size and significance of genetic and environmental risks in PD traits shared with CU and CUD. DESIGN:Linear mixed-effects models were used to identify PD traits for inclusion in twin analyses to explore the genetic and environmental associations between the traits and cannabis use. SETTING:Cross-sectional data were obtained from Norwegian adult twins in a face-to-face interview in 1999-2004 as part of a population-based study of mental health. PARTICIPANTS:Subjects were 1419 twins (?age = 28.2 years, range = 19-36) from the Norwegian Institute of Public Health Twin Panel with complete PD and cannabis data. MEASUREMENTS:PD traits were assessed using DSM-IV criteria. Life-time CU and CUD were based on DSM-IV abuse and dependence criteria, including withdrawal and craving. FINDINGS:After adjusting for age and sex, antisocial [? = 0.23, 95% confidence interval (CI) = 0.19-0.28] and borderline PDs (? = 0.20, 95% CI = 0.14-0.26) were associated strongly with CU. Antisocial (? = 0.26, 95% CI = 0.21-0.31) and borderline PDs (? = 0.12, 95% CI = 0.06-0.18) were also linked strongly to CUD. Genetic risks in antisocial and borderline PD traits explained 32-60% of the total variance in CU and CUD. Dependent and avoidant PDs explained 11 and 16% of the total variance in CU and CUD, respectively. CONCLUSIONS:Individual differences in the liability to cannabis use and cannabis use disorder appear to be linked to genetic risks correlated with antisocial and borderline personality disorder traits.
Project description:The main objective of this prospective longitudinal study was to investigate bidirectional associations between adolescent cannabis use (CU) and neurocognitive performance in a community sample of 294 young men from ages 13 to 20 years. The results showed that in early adolescence, and prior to initiation to CU, poor short-term and working memory, but high verbal IQ, were associated with earlier age of onset of CU. In turn, age of CU onset and CU frequency across adolescence were associated with (a) specific neurocognitive decline in verbal IQ and executive function tasks tapping trial and error learning and reward processing by early adulthood and (b) lower rates of high-school graduation. The association between CU onset and change in neurocognitive function, however, was found to be accounted for by CU frequency. Whereas the link between CU frequency across adolescence and change in verbal IQ was explained (mediated) by high school graduation, the link between CU frequency and tasks tapping trial and error learning were independent from high school graduation, concurrent cannabis and other substance use, adolescent alcohol use, and externalizing behaviors. Findings support prevention efforts aimed at delaying onset and reducing frequency of CU.
Project description:Multiple forms of drug abuse/dependence frequently co-occur with problem/pathological gambling (PPG). The current study examines the extent to which genetic and environmental factors contribute to their co-occurrence.Bivariate models investigated the magnitude and correlation of genetic and environmental contributions to problem/pathological gambling and its co-occurrence with nicotine dependence, cannabis abuse/dependence and stimulant abuse/dependence.Computer-assisted telephone interviews in the community.Participants were 7869 male twins in the Vietnam Era Twin Registry, a USA-based national twin registry.Life-time DSM-III-R diagnoses for problem/pathological gambling, nicotine dependence, cannabis abuse/dependence and stimulant abuse/dependence were determined using the Diagnostic Interview Schedule.All drug-use disorders displayed additive genetic and non-shared environmental contributions, with cannabis abuse/dependence also displaying shared environmental contributions. Both genetic [genetic correlation rA ?=?0.22; 95% confidence interval (CI)?=?0.10-0.34] and non-shared environmental components (environmental correlation rE ?=?0.24; 95% CI?=?0.10-0.37) contributed to the co-occurrence of problem/pathological gambling and nicotine dependence. This pattern was shared by cannabis abuse/dependence (rA ?=?0.32; 95% CI?=?0.05-1.0; rE ?=?0.36; 95% CI?=?0.16-0.55) but not stimulant abuse/dependence (SAD), which showed only genetic contributions to the co-occurrence with problem/pathological gambling (rA ?=?0.58; 95% CI?=?0.45-0.73).Strong links between gambling and stimulant-use disorders may relate to the neurochemical properties of stimulants or the illicit nature of using 'hard' drugs such as cocaine. The greater contribution of environmental factors to the co-occurrence between problem/pathological gambling and 'softer' forms of drug abuse/dependence (cannabis, tobacco) suggest that environmental interventions (perhaps relating to availability and legality) may help to diminish the relationship between problem/pathological gambling and tobacco- and cannabis-use disorders.
Project description: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.