Association Between Stimulant Treatment and Substance Use Through Adolescence Into Early Adulthood.

Importance: Possible associations between stimulant treatment of attention-deficit/hyperactivity disorder (ADHD) and subsequent substance use remain debated and clinically relevant. Objective: To assess the association of stimulant treatment of ADHD with subsequent substance use using the Multimodal Treatment Study of ADHD (MTA), which provides a unique opportunity to test this association while addressing methodologic complexities (principally, multiple dynamic confounding variables). Design, Setting, and Participants: MTA was a multisite study initiated at 6 sites in the US and 1 in Canada as a 14-month randomized clinical trial of medication and behavior therapy for ADHD but transitioned to a longitudinal observational study. Participants were recruited between 1994 and 1996. Multi-informant assessments included comprehensively assessed demographic, clinical (including substance use), and treatment (including stimulant treatment) variables. Children aged 7 to 9 years with rigorously diagnosed DSM-IV combined-type ADHD were repeatedly assessed until a mean age of 25 years. Analysis took place between April 2018 and February 2023. Exposure: Stimulant treatment of ADHD was measured prospectively from baseline for 16 years (10 assessments) initially using parent report followed by young adult report. Main Outcomes and Measures: Frequency of heavy drinking, marijuana use, daily cigarette smoking, and other substance use were confidentially self-reported with a standardized substance use questionnaire. Results: A total of 579 children (mean [SD] age at baseline, 8.5 [0.8] years; 465 [80%] male) were analyzed. Generalized multilevel linear models showed no evidence that current (B [SE] range, -0.62 [0.55] to 0.34 [0.47]) or prior stimulant treatment (B [SE] range, -0.06 [0.26] to 0.70 [0.37]) or their interaction (B [SE] range, -0.49 [0.70] to 0.86 [0.68]) were associated with substance use after adjusting for developmental trends in substance use and age. Marginal structural models adjusting for dynamic confounding by demographic, clinical, and familial factors revealed no evidence that more years of stimulant treatment (B [SE] range, -0.003 [0.01] to 0.04 [0.02]) or continuous, uninterrupted stimulant treatment (B [SE] range, -0.25 [0.33] to -0.03 [0.10]) were associated with adulthood substance use. Findings were the same for substance use disorder as outcome. Conclusions and Relevance: This study found no evidence that stimulant treatment was associated with increased or decreased risk for later frequent use of alcohol, marijuana, cigarette smoking, or other substances used for adolescents and young adults with childhood ADHD. These findings do not appear to result from other factors that might drive treatment over time and findings held even after considering opposing age-related trends in stimulant treatment and substance use.

Substance use through adolescence into early adulthood after childhood-diagnosed ADHD: findings from the MTA longitudinal study.

BACKGROUND: Inconsistent findings exist regarding long-term substance use (SU) risk for children diagnosed with attention-deficit/hyperactivity disorder (ADHD). The observational follow-up of the Multimodal Treatment Study of Children with ADHD (MTA) provides an opportunity to assess long-term outcomes in a large, diverse sample. METHODS: Five hundred forty-seven children, mean age 8.5, diagnosed with DSM-IV combined-type ADHD and 258 classmates without ADHD (local normative comparison group; LNCG) completed the Substance Use Questionnaire up to eight times from mean age 10 to mean age 25. RESULTS: In adulthood, weekly marijuana use (32.8% ADHD vs. 21.3% LNCG) and daily cigarette smoking (35.9% vs. 17.5%) were more prevalent in the ADHD group than the LNCG. The cumulative record also revealed more early substance users in adolescence for ADHD (57.9%) than LNCG (41.9%), including younger first use of alcohol, cigarettes, marijuana, and illicit drugs. Alcohol and nonmarijuana illicit drug use escalated slightly faster in the ADHD group in early adolescence. Early SU predicted quicker SU escalation and more SU in adulthood for both groups. CONCLUSIONS: Frequent SU for young adults with childhood ADHD is accompanied by greater initial exposure at a young age and slightly faster progression. Early SU prevention and screening is critical before escalation to intractable levels.

Does Congenital Heart Disease Affect Neurodevelopmental Outcomes in Children with Down Syndrome?

OBJECTIVE: The impact that congenital heart disease (CHD) has on the neurodevelopment of children with Down syndrome (DS) is unknown and potentially has implications for targeted early intervention. This study assessed the relationship between CHD that required surgery in the first year of life and neurodevelopmental, behavioral and emotional functioning outcomes in children with DS. METHODS: A retrospective chart review of 1092 children (0-18 years) with DS who visited a single institution from 8/08-8/13 was performed. Children who underwent at least one of nine neurodevelopmental (cognitive, language, developmental) or academic tests were included in the analysis (N = 178). Cohort was age-divided into infants/toddlers (0-2 years), preschoolers (3-5 years), and school age/adolescent (6-18 years). Test scores of children with DS who underwent cardiac surgery in the first year of life were compared to children with DS without CHD. T test, chi-square and Mann Whitney U tests were used where appropriate. RESULTS: Infants/toddlers with cardiac surgery had lower scores for receptive (P = .01), expressive (P = .021) and composite language (P < .001) compared to those with no CHD. Preschoolers with cardiac surgery had lower language scores and lower visual motor scores, although not statistically significant. In school age children with cardiac surgery there were no differences in IQ scores, language scores, or academic achievement scores compared to those without CHD. Also at school-age there was no difference in the incidence of ADHD, executive function or on internalizing and externalizing behavior scores. CONCLUSION: Children with DS undergoing cardiac surgery during the first year demonstrated poorer neurodevelopmental outcomes as infants/toddler but had no difference at school age compared to children with DS without CHD. These results will guide early interventions to optimize neurodevelopmental outcomes in children with DS and will help with family counseling after CHD repair.

The impact of ADHD persistence, recent cannabis use, and age of regular cannabis use onset on subcortical volume and cortical thickness in young adults.

BACKGROUND: Both Attention Deficit Hyperactivity Disorder (ADHD) and chronic cannabis (CAN) use have been associated with brain structural abnormalities, although little is known about the effects of both in young adults. METHODS: Participants included: those with a childhood diagnosis of ADHD who were CAN users (ADHD_CAN; n=37) and non-users (NU) (ADHD_NU; n=44) and a local normative comparison group (LNCG) who did (LNCG_CAN; n=18) and did not (LNCG_NU; n=21) use CAN regularly. Multiple regressions and MANCOVAs were used to examine the independent and interactive effects of a childhood ADHD diagnosis and CAN group status and age of onset (CUO) on subcortical volumes and cortical thickness. RESULTS: After controlling for age, gender, total brain volume, nicotine use, and past-year binge drinking, childhood ADHD diagnosis did not predict brain structure; however, persistence of ADHD was associated with smaller left precentral/postcentral cortical thickness. Compared to all non-users, CAN users had decreased cortical thickness in right hemisphere superior frontal sulcus, anterior cingulate, and isthmus of cingulate gyrus regions and left hemisphere superior frontal sulcus and precentral gyrus regions. Early cannabis use age of onset (CUO) in those with ADHD predicted greater right hemisphere superior frontal and postcentral cortical thickness. DISCUSSION: Young adults with persistent ADHD demonstrated brain structure abnormalities in regions underlying motor control, working memory and inhibitory control. Further, CAN use was linked with abnormal brain structure in regions with high concentrations of cannabinoid receptors. Additional large-scale longitudinal studies are needed to clarify how substance use impacts neurodevelopment in youth with and without ADHD.

ADHD and cannabis use in young adults examined using fMRI of a Go/NoGo task.

Children diagnosed with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for substance abuse. Response inhibition is a hallmark of ADHD, yet the combined effects of ADHD and regular substance use on neural networks associated with response inhibition are unknown. Task-based functional Magnetic Resonance Imaging (fMRI) data from young adults with childhood ADHD with (n = 25) and without (n = 25) cannabis use ≥ monthly in the past year were compared with a local normative comparison group (LNCG) with (n = 11) and without (n = 12) cannabis use. Go/NoGo behavioral and fMRI data were evaluated for main and interaction effects of ADHD diagnosis and cannabis use. ADHD participants made significantly more commission errors on NoGo trials than controls. ADHD participants also had less frontoparietal and frontostriatal activity, independent of cannabis use. No main effects of cannabis use on response inhibition or functional brain activation were observed. An interaction of ADHD diagnosis and cannabis use was found in the right hippocampus and cerebellar vermis, with increased recruitment of these regions in cannabis-using controls during correct response inhibition. ADHD participants had impaired response inhibition combined with less fronto-parietal/striatal activity, regardless of cannabis use history. Cannabis use did not impact behavioral response inhibition. Cannabis use was associated with hippocampal and cerebellar activation, areas rich in cannabinoid receptors, in LNCG but not ADHD participants. This may reflect recruitment of compensatory circuitry in cannabis using controls but not ADHD participants. Future studies targeting hippocampal and cerebellar-dependent function in these groups may provide further insight into how this circuitry is altered by ADHD and cannabis use.

Association of attention-deficit/hyperactivity disorder and conduct disorder with early tobacco and alcohol use.

BACKGROUND: The association of attention-deficit/hyperactivity disorder (ADHD) and conduct disorder (CD) with tobacco and alcohol use has not been assessed in a young adolescent sample representative of the U.S. population. METHODS: Data are from the 2000-2004 National Health and Nutrition Examination Survey, a cross-sectional sample representative of the U.S. population. Participants were age 12-15 years (N=2517). Exposure variables included diagnosis of ADHD and CD, and counts of ADHD and CD symptoms based on caregiver responses to the Diagnostic Interview Schedule for Children. Primary outcomes were adolescent-report of any use of tobacco or alcohol and age of initiating use. Multivariate logistic regression and Cox proportional hazard models were conducted. RESULTS: Adolescents with ADHD+CD diagnoses had a 3- to 5-fold increased likelihood of using tobacco and alcohol and initiated use at a younger age compared to those with neither disorder. Having ADHD alone was associated with an increased likelihood of tobacco use but not alcohol use. Hyperactive-impulsive symptom counts were not independently associated with any outcome, while every one symptom increase in inattention increased the likelihood of tobacco and alcohol use by 8-10%. Although participants with a diagnosis of CD alone (compared to those without ADHD or CD) did not have a higher likelihood of tobacco or alcohol use, for every one symptom increase in CD symptoms the odds of tobacco use increased by 31%. CONCLUSIONS: ADHD and CD diagnoses and symptomatology are linked to higher risk for a range of tobacco and alcohol use outcomes among young adolescents in the U.S.

Impact of ADHD and cannabis use on executive functioning in young adults.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) and cannabis use are each associated with specific cognitive deficits. Few studies have investigated the neurocognitive profile of individuals with both an ADHD history and regular cannabis use. The greatest cognitive impairment is expected among ADHD Cannabis Users compared to those with ADHD-only, Cannabis use-only, or neither. METHODS: Young adults (24.2 ± 1.2 years) with a childhood ADHD diagnosis who did (n=42) and did not (n=45) report past year ≥ monthly cannabis use were compared on neuropsychological measures to a local normative comparison group (LNCG) who did (n=20) and did not (n=21) report past year regular cannabis use. Age, gender, IQ, socioeconomic status, and past year alcohol and smoking were statistical covariates. RESULTS: The ADHD group performed worse than LNCG on verbal memory, processing speed, cognitive interference, decision-making, working memory, and response inhibition. No significant effects for cannabis use emerged. Interactions between ADHD and cannabis were non-significant. Exploratory analyses revealed that individuals who began using cannabis regularly before age 16 (n=27) may have poorer executive functioning (i.e., decision-making, working memory, and response inhibition), than users who began later (n=32); replication is warranted with a larger sample. CONCLUSIONS: A childhood diagnosis of ADHD, but not cannabis use in adulthood, was associated with executive dysfunction. Earlier initiation of cannabis use may be linked to poor cognitive outcomes and a significantly greater proportion of the ADHD group began using cannabis before age 16. Regular cannabis use starting after age 16 may not be sufficient to aggravate longstanding cognitive deficits characteristic of ADHD.

Association of tobacco and lead exposures with attention-deficit/hyperactivity disorder.

OBJECTIVE: The study objective was to determine the independent and joint associations of prenatal tobacco and childhood lead exposures with attention-deficit/hyperactivity disorder (ADHD), as defined by current diagnostic criteria, in a national sample of US children. METHODS: Data are from the 2001-2004 National Health and Nutrition Examination Survey, a cross-sectional, nationally representative sample of the US population. Participants were 8 to 15 years of age (N = 2588). Prenatal tobacco exposure was measured by report of maternal cigarette use during pregnancy. Lead exposure was assessed by using current blood lead levels. The Diagnostic Interview Schedule for Children was used to ascertain the presence of ADHD in the past year, on the basis of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. RESULTS: A total of 8.7% (95% confidence interval [CI]: 7.3%-10.1%) of children met criteria for ADHD. Prenatal tobacco exposure (adjusted odds ratio [aOR]: 2.4 [95% CI: 1.5-3.7]) and higher current blood lead concentrations (aOR for third versus first tertile: 2.3 [95% CI: 1.5-3.8]) were independently associated with ADHD. Compared with children with neither exposure, children with both exposures (prenatal tobacco exposure and third-tertile lead levels) had an even greater risk of ADHD (aOR: 8.1 [95% CI: 3.5-18.7]) than would be expected if the independent risks were multiplied (tobacco-lead exposure interaction term, P < .001). CONCLUSIONS: Prenatal tobacco and childhood lead exposures are associated with ADHD in US children, especially among those with both exposures. Reduction of these common toxicant exposures may be an important avenue for ADHD prevention.