John L. Moulton

Age of Methylphenidate Treatment Initiation in Children with ADHD and Later Substance Abuse: Prospective Follow-Up into Adulthood

OBJECTIVE Animal studies have shown that age at stimulant exposure is positively related to later drug sensitivity. The purpose of this study was to examine whether age at initiation of stimulant treatment in children with attention deficit hyperactivity disorder (ADHD) is related to the subsequent development of substance use disorders. METHOD The authors conducted a prospective longitudinal study of 176 methylphenidate-treated Caucasian male children (ages 6 to 12) with ADHD but without conduct disorder. The participants were followed up at late adolescence (mean age=18.4 years; retention rate=94%) and adulthood (mean age=25.3; retention rate=85%). One hundred seventy-eight comparison subjects also were included. All subjects were diagnosed by blinded clinicians. The Cox proportional hazards model included the following childhood predictor variables: age at initiation of methylphenidate treatment, total cumulative dose of methylphenidate, treatment duration, IQ, severity of hyperactivity, socioeconomic status, and lifetime parental psychopathology. Separate models tested for the following four lifetime outcomes: any substance use disorder, alcohol use disorder, non-alcohol substance use disorder, and stimulant use disorder. Other outcomes included antisocial personality, mood, and anxiety disorders. RESULTS There was a significant positive relationship between age at treatment initiation and non-alcohol substance use disorder. None of the predictor variables accounted for this association. Post hoc analyses showed that the development of antisocial personality disorder explained the relationship between age at first methylphenidate treatment and later substance use disorder. Even when controlling for substance use disorder, age at stimulant treatment initiation was significantly and positively related to the later development of antisocial personality disorder. Age at first methylphenidate treatment was unrelated to mood and anxiety disorders. CONCLUSIONS Early age at initiation of methylphenidate treatment in children with ADHD does not increase the risk for negative outcomes and may have beneficial long-term effects.

Lifetime criminality among boys with attention deficit hyperactivity disorder: a prospective follow-up study into adulthood using official arrest records.

This study investigates the relationship between childhood attention deficit hyperactivity disorder (ADHD) and later criminality. White boys (n=207, ages 6-12) with ADHD, free of conduct disorder, were assessed at ages 18 and 25 by clinicians who were blind to childhood status. A non-ADHD group served as comparisons. Lifetime arrest records were obtained when subjects were 38 years old for subjects who resided in New York State throughout the follow-up interval (93 probands, 93 comparisons). Significantly more ADHD probands than comparisons had been arrested (47% vs. 24%), convicted (42% vs. 14%), and incarcerated (15% vs. 1%). Rates of felonies and aggressive offenses also were significantly higher among probands. Importantly, the development of an antisocial or substance use disorder in adolescence completely explained the increased risk for subsequent criminality. Results suggest that even in the absence of comorbid conduct disorder in childhood, ADHD increases the risk for developing antisocial and substance use disorders in adolescence, which, in turn, increases the risk for criminal behavior in adolescence and adulthood.

Persistence of Attention-Deficit/Hyperactivity Disorder into adulthood: What have we learned from the prospective follow-up studies?

Objectives: Longitudinal studies of children with Attention-Deficit/Hyperactivity Disorder (ADHD) into adolescence have all reported high rates of ADHD. However, findings from studies into adulthood are inconsistent. This article reviews factors that may account for disparate rates found in adult follow-ups, and recommends optimal methodologies for prospective studies of children with ADHD in particular and childhood mental disorders in general. Method: Follow-up studies of children with ADHD into adulthood are critically reviewed to identify factors that influence adult ADHD prevalence estimates. Results: Four factors are identified: (1) ascertainment procedure, (2) attrition rate, (3) reporting source, and (4) disorder criteria. Conclusions: Estimates of the proportion of children with ADHD who will experience symptoms of the childhood syndrome in adulthood are likely to vary considerably, as a function of multiple factors. Several recommendations are made for designing future follow-up investigations.

Does stimulant treatment place children at risk for adult substance abuse? A controlled, prospective follow-up study.

The sensitization hypothesis posits a neuroadaptation model in which exposure to stimulants results in dopamine system alterations that, in turn, increase sensitivity to the reinforcing effects of the previously experienced drug. This study examines whether stimulant treatment in childhood confers increased risk for substance use and abuse in later life, as the model predicts. Children, ages 7-12 years, with developmental reading disorders but no other psychiatric diagnoses were randomly assigned to methylphenidate treatment (n = 43) or matching placebo (n = 66) for 12-18 weeks. At 16-year follow-up (mean age 26 years), 94% of probands and 129 normal comparisons were evaluated by trained clinicians who were blind to group and treatment status. There were no significant differences between groups on the prevalence of substance use disorder (abuse or dependence) for any of the seven drug categories studied. There were no significant group differences among substance abusers regarding age at onset, duration, or number of episodes of substance abuse and dependence. Significantly more normals (60%) than treated (46%) and untreated probands (41%) ever used stimulants in adolescence or adulthood. Findings from this randomized trial contradict the notion that stimulant treatment in childhood leads to substance use or abuse in later life. The sensitization hypothesis is not supported.

Relationship Between Separation Anxiety Disorder, Parental Panic Disorder, and Atopic Disorders in Children: A Controlled High-Risk Study

OBJECTIVE To test the hypotheses that rates of atopic disorders are elevated in offspring of parents with panic disorder (PD) and in children with separation anxiety disorder (SAD). METHOD Rates of atopic disorders were assessed in 343 offspring (aged 6-17 years) of parents with PD, nonpanic psychiatric disorders, and no psychiatric disorder. Lifetime history of atopic disorders was determined by parental responses to a clinician-administered questionnaire assessing medical treatment for asthma and allergies. Logistic regression analyses assessed the association between atopic disorders and parental PD, and between atopic disorders and probable or definite childhood SAD. Analyses controlled for age, sex, socioeconomic status, and treatment for other medical illnesses. RESULTS Increased rates of atopic disorders were found in offspring of parents with PD (odds ratio [OR] = 2.56, 95% confidence interval [CI] = 1.27-5.16, p = .009) and in children with SAD (OR = 2.71, 95% Cl = 1.22-6.03, p = .015). Associations remained significant when both parental PD and SAD were included in the model, suggesting that each contributed independently to increased rates of atopy. The interaction of parental PD and child SAD was not significant. CONCLUSIONS Atopic disorders in children are associated with parental PD and with childhood SAD. Results do not appear to support that having both childhood SAD and a parent with PD confers increased risk for atopic disorders above and beyond either condition alone.

Anxiety sensitivity among children of parents with anxiety disorders: a controlled high-risk study

We investigated whether parental anxiety was related to anxiety sensitivity (AS) in offspring. Subjects were 261 offspring (aged 6-17 years) of parents with lifetime DSM-IV anxiety and/or mood disorders, and 79 offspring of parents with no lifetime anxiety, mood, or psychotic disorder. Parents and offspring were interviewed by blind clinicians. Children were administered the Child Anxiety Sensitivity Index (CASI). There were no significant differences between CASI scores of the offspring of parents with anxiety and/or mood disorders, and offspring of comparison parents. We conclude that parental anxiety or mood disorder does not predispose offspring to high anxiety sensitivity.