Eric Mick

Young adult outcome of attention deficit hyperactivity disorder: a controlled 10-year follow-up study

BACKGROUND Our objective was to estimate the lifetime prevalence of psychopathology in a sample of youth with and without attention deficit hyperactivity disorder (ADHD) through young adulthood using contemporaneous diagnostic and analytic techniques. METHOD We conducted a case-control, 10-year prospective study of ADHD youth. At baseline, we assessed consecutively referred male, Caucasian children with (n=140) and without (n=120) DSM-III-R ADHD, aged 6-18 years, ascertained from psychiatric and pediatric sources to allow for generalizability of results. At the 10-year follow-up, 112 (80%) and 105 (88%) of the ADHD and control children, respectively, were reassessed (mean age 22 years). We created the following categories of psychiatric disorders: Major Psychopathology (mood disorders and psychosis), Anxiety Disorders, Antisocial Disorders (conduct, oppositional-defiant, and antisocial personality disorder), Developmental Disorders (elimination, language, and tics disorder), and Substance Dependence Disorders (alcohol, drug, and nicotine dependence), as measured by blinded structured diagnostic interview. RESULTS The lifetime prevalence for all categories of psychopathology were significantly greater in ADHD young adults compared to controls, with hazard ratios and 95% confidence intervals of 6.1 (3.5-10.7), 2.2 (1.5-3.2), 5.9 (3.9-8.8), 2.5 (1.7-3.6), and 2.0 (1.3-3.0), respectively, for the categories described above. CONCLUSIONS By their young adult years, ADHD youth were at high risk for a wide range of adverse psychiatric outcomes including markedly elevated rates of antisocial, addictive, mood and anxiety disorders. These prospective findings provide further evidence for the high morbidity associated with ADHD across the life-cycle and stress the importance of early recognition of this disorder for prevention and intervention strategies.

Is ADHD a Risk Factor for Psychoactive Substance Use Disorders? Findings From a Four-Year Prospective Follow-up Study

ABSTRACT Objective To evaluate whether attention-deficit hyperactivity disorder (ADHD) is a risk factor for psychoactive substance use disorders (PSUD), attending to issues of psychiatric comorbidity, family history, and adversity. Method Using assessments from multiple domains, the authors examined 140 ADHD and 120 normal control subjects at baseline and 4 years later. Drug and alcohol abuse and dependence were operationally defined. Results No differences were detected in the rates of alcohol or drug abuse or dependence or in the rates of abuse of individual substances between the groups; both ADHD and control probands had a 15% rate of PSUD. Conduct and bipolar disorders predicted PSUD, independently of ADHD status. Family history of substance dependence and antisocial disorders was associated with PSUD in controls but less clearly so in ADHD probands. Family history of ADHD was not associated with risk for PSUD. ADHD probands had a significantly shorter time period between the onsets of abuse and dependence compared with controls (1.2 years versus 3 years, p Conclusions Adolescents with and without ADHD had a similar risk for PSUD that was mediated by conduct and bipolar disorder. Since the risk for PSUD has been shown to be elevated in adults with ADHD when compared with controls, a sharp increase in PSUD is to be expected in grown-up ADHD children during the transition from adolescence to adulthood.

Case-Control Study of Attention-Deficit Hyperactivity Disorder and Maternal Smoking, Alcohol Use, and Drug Use During Pregnancy

OBJECTIVE To address the putative association between attention-deficit hyperactivity disorder (ADHD) and prenatal exposure to maternal cigarette smoking, drugs of abuse, and alcohol attending to potential confounding by familial ADHD, maternal depression, conduct disorder, and indicators of social adversity in the environment. METHOD A retrospective, hospital-based, case-control study was conducted with 280 ADHD cases and 242 non-ADHD controls of both genders. The case and control children and their relatives were systematically assessed with structured diagnostic interviews. Logistic regression analysis was used to determine the adjusted effect of prenatal exposure to substance use and ADHD. RESULTS ADHD cases were 2.1 times (95% confidence interval = 1.1-4.1;p = .02) more likely to have been exposed to cigarettes and 2.5 times (95% confidence interval = 1.1-5.5; p = .03) more likely to have been exposed to alcohol in utero than were the non-ADHD control subjects. Adjustment by familial psychopathology, Rutters indicators of social adversity, and comorbid conduct disorder did not account for the effect of prenatal exposure to alcohol or the products of cigarettes. CONCLUSIONS ADHD may be an additional deleterious outcome associated with prenatal exposure to alcohol independently of the association between prenatal exposure to nicotine and smoke products and other familial risk factors for the disorder.

Pharmacotherapy of attention-deficit/hyperactivity disorder reduces risk for substance use disorder.

Objective. To assess the risk for substance use disorders (SUD) associated with previous exposure to psychotropic medication in a longitudinal study of boys with attention-deficit/hyperactivity disorder (ADHD). Methods. The cumulative incidence of SUD throughout adolescence was compared in 56 medicated subjects with ADHD, 19 nonmedicated subjects with ADHD, and 137 non-ADHD control subjects. Results. Unmedicated subjects with ADHD were at a significantly increased risk for any SUD at follow-up compared with non-ADHD control subjects (adjusted OR: 6.3 [1.8–21.6]). Subjects with ADHD medicated at baseline were at a significantly reduced risk for a SUD at follow-up relative to untreated subjects with ADHD (adjusted OR: 0.15 [0.04–0.6]). For each SUD subtype studied, the direction of the effect of exposure to pharmacotherapy was similar to that seen for the any SUD category. Conclusions. Consistent with findings in untreated ADHD in adults, untreated ADHD was a significant risk factor for SUD in adolescence. In contrast, pharmacotherapy was associated with an 85% reduction in risk for SUD in ADHD youth.

Attention-Deficit Hyperactivity Disorder and Juvenile Mania: An Overlooked Comorbidity?

OBJECTIVE To evaluate the psychiatric, cognitive, and functional correlates of attention-deficit hyperactivity disorder (ADHD) children with and without comorbid bipolar disorder (BPD). METHOD DSM-III-R structured diagnostic interviews and blind raters were used to examine psychiatric diagnoses at baseline and 4-year follow-up in ADHD and control children. In addition, subjects were evaluated for cognitive, academic, social, school, and family functioning. RESULTS BPD was diagnosed in 11% of ADHD children at baseline and in an additional 12% at 4-year follow-up. These rates were significantly higher than those of controls at each assessment. ADHD children with comorbid BPD at either baseline or follow-up assessment had significantly higher rates of additional psychopathology, psychiatric hospitalization, and severely impaired psychosocial functioning than other ADHD children. The clinical picture of bipolarity was mostly irritable and mixed. ADHD children with comorbid BPD also had a very severe symptomatic picture of ADHD as well as prototypical correlates of the disorder. Comorbidity between ADHD and BPD was not due to symptom overlap. ADHD children who developed BPD at the 4-year follow-up had higher initial rates of comorbidity, more symptoms of ADHD, worse scores on the CBCL, and a greater family history of mood disorder compared with non-BPD, ADHD children. CONCLUSIONS The results extend previous results documenting that children with ADHD are at increased risk of developing BPD with its associated severe morbidity, dysfunction, and incapacitation.

Molecular Genetics of Attention Deficit Hyperactivity Disorder

Although twin studies demonstrate that ADHD is a highly heritable condition, molecular genetic studies suggest that the genetic architecture of ADHD is complex. The handful of genome-wide linkage and association scans that have been conducted thus far show divergent findings and are, therefore, not conclusive. Similarly, many of the candidate genes reviewed here (ie, DBH, MAOA, SLC6A2, TPH-2, SLC6A4, CHRNA4, GRIN2A) are theoretically compelling from neurobiological systems perspective but available data are sparse and inconsistent. However, candidate gene studies of ADHD have produced substantial evidence implicating several genes in the etiology of the disorder, with meta-analyses supportive of a role of the genes coding for DRD4, DRD5, SLC6A3, SNAP-25, and HTR1B in the etiology of ADHD.

Genetics of Attention Deficit Hyperactivity Disorder

Results of behavioral genetic and molecular genetic studies have converged to suggest that both genetic and nongenetic factors contribute to the development of attention deficit hyperactivity disorder (ADHD). Family, twin, and adoption studies provide compelling evidence that genes play a strong role in mediating susceptibility to ADHD. In contrast to a handful of genome-wide scans conducted thus far, many candidate gene studies of ADHD have produced substantial evidence implicating several genes in the etiology of the disorder. Yet, even these associations are small and consistent with the idea that the genetic vulnerability to ADHD is mediated by many genes of small effects. These small effects emphasize the need for future candidate gene studies to implement strategies that will provide enough statistical power to detect such small effects.

Clinical correlates of ADHD in females : Findings from a large group of girls ascertained from pediatric and psychiatric referral sources

OBJECTIVE The scientific literature about attention-deficit hyperactivity disorder (ADHD) is based almost exclusively on male subjects, and girls with ADHD may be underidentified and undertreated. The aim of this study was to examine clinical correlates of ADHD in females using comprehensive assessments in multiple domains of functioning. METHOD Subjects were 140 girls with ADHD and 122 comparison girls without ADHD ascertained from pediatric and psychiatric referral sources of the same age and social class. Subjects were assessed with structured diagnostic interviews, psychometric tests assessing intellectual functioning and academic achievement, as well as standardized assessments of interpersonal, school, and family functioning by raters who were blind to clinical diagnosis. RESULTS Compared with female controls, girls with ADHD were more likely to have conduct, mood, and anxiety disorders; lower IQ and achievement scores; and more impairment on measures of social, school, and family functioning. CONCLUSIONS These results extend to girls previous findings in boys indicating that ADHD is characterized by prototypical core symptoms of the disorder, high levels of comorbid psychopathology, and dysfunction in multiple domains. These results not only support findings documenting phenotypic similarities between the genders but also stress the severity of the disorder in females.

Meta-analysis of genome-wide association studies of attention-deficit/hyperactivity disorder

OBJECTIVE Although twin and family studies have shown attention-deficit/hyperactivity disorder (ADHD) to be highly heritable, genetic variants influencing the trait at a genome-wide significant level have yet to be identified. As prior genome-wide association studies (GWAS) have not yielded significant results, we conducted a meta-analysis of existing studies to boost statistical power. METHOD We used data from four projects: a) the Childrens Hospital of Philadelphia (CHOP); b) phase I of the International Multicenter ADHD Genetics project (IMAGE); c) phase II of IMAGE (IMAGE II); and d) the Pfizer-funded study from the University of California, Los Angeles, Washington University, and Massachusetts General Hospital (PUWMa). The final sample size consisted of 2,064 trios, 896 cases, and 2,455 controls. For each study, we imputed HapMap single nucleotide polymorphisms, computed association test statistics and transformed them to z-scores, and then combined weighted z-scores in a meta-analysis. RESULTS No genome-wide significant associations were found, although an analysis of candidate genes suggests that they may be involved in the disorder. CONCLUSIONS Given that ADHD is a highly heritable disorder, our negative results suggest that the effects of common ADHD risk variants must, individually, be very small or that other types of variants, e.g., rare ones, account for much of the disorders heritability.

A large, double-blind, randomized clinical trial of methylphenidate in the treatment of adults with attention-deficit/hyperactivity disorder

BACKGROUND The few controlled studies of methylphenidate (MPH) in adults with attention deficit/hyperactivity disorder (ADHD) have reported equivocal results. A previous, pilot study by our group suggested that these results were due to inadequate dosing. METHOD We conducted a randomized, 6-week, placebo-controlled, parallel study of MPH in 146 adult patients with DSM-IV ADHD using standardized instruments for diagnosis, separate assessments of ADHD, depressive and anxiety symptoms, and a robust average oral daily dose of 1.1 mg/kg/day. RESULTS We found a marked therapeutic response for the MPH treatment of ADHD symptoms that exceeded the placebo response (76% vs. 19%). Treatment was safe and well tolerated. Response to MPH was independent of socioeconomic status, gender, and lifetime history of psychiatric comorbidity. CONCLUSIONS These results confirm that robust doses of MPH are effective in the treatment of adult ADHD.