Adult Psychiatric Outcomes of Girls With Attention Deficit Hyperactivity Disorder: 11-Year Follow-Up in a Longitudinal Case-Control Study

Details of the study methods have been reported elsewhere (4, 8). Participants were from a longitudinal case-control family study of girls with and without ADHD. At baseline, we ascertained girls 6–17 years of age with (N=140) and without (N=122) DSM-III-R-defined ADHD from pediatric and psychiatric clinics. We excluded patients who had been adopted, those whose nuclear family was not available for study, and those who had major sensorimotor disabilities (paralysis, deafness, blindness), psychosis, autism, inadequate command of the English language, or a full-scale IQ below 80. All girls in the ADHD group met DSM-III-R criteria for ADHD at the time of the clinical referral, and all had active symptoms of the disorder at the time of recruitment. Participants were recruited irrespective of comorbid disorders.

In this study, we analyzed data on 96 girls with ADHD and 91 comparison girls from the original sample who completed a full follow-up assessment a mean of 11 years (range=8 to 14 years) after enrollment. Participants ranged from 15 to 30 years of age (mean=22.1 years, SD=3.3) at follow-up. Eighty-three (86%) of the girls in the ADHD group and 90 (99%) of those in the comparison group had reached age 18 by the 11-year follow-up. Participants provided written informed consent, and parents also provided consent for offspring under the age of 18 and for their report on their offspring. Adolescents provided written assent to participate. The human research committee at Massachusetts General Hospital approved this study.

We used the Structured Clinical Interview for DSM-IV (SCID) (11) supplemented with modules from the DSM-IV modified Schedule for Affective Disorders and Schizophrenia for School-Age Children–Epidemiologic Version (K-SADS-E) (12) to assess childhood diagnoses. The K-SADS-E was used for participants under age 18. We interviewed all participants and interviewed their mothers about their offspring. Of the 187 girls for whom a full diagnostic interview was conducted, the proportion for whom we had direct only, mother only, and both types of reports were 89%, 3%, and 8%, respectively (47%, 3%, and 50%, respectively, for the ADHD module). We combined data from direct and indirect interviews by considering a diagnostic criterion positive if it was endorsed in either interview.

Interviewers were blind to baseline ascertainment group, ascertainment site, and prior assessments. They had undergraduate degrees in psychology and were extensively trained. The principal investigator (J.B.) supervised them throughout the study. Kappa coefficients between interviewers and board-certified child and adult psychiatrists and licensed clinical psychologists have been reported elsewhere (8); the median kappa coefficient for individual disorders was 0.98.

We considered a disorder present if DSM-IV diagnostic criteria were unequivocally met. Diagnostic uncertainties were resolved by a committee of board-certified child and adult psychiatrists and child psychologists blind to the participant's ADHD status, referral source, and all other data. Diagnoses presented for review were considered positive only if diagnostic criteria were met to a clinically meaningful degree. We estimated the reliability of the diagnostic review process by computing kappa coefficients of agreement for clinician reviewers. Kappa coefficients between individual clinicians and the review committee have been reported elsewhere (8); the median kappa coefficient for individual disorders was 0.87. Participants were asked to describe the degree of impairment in daily functioning associated with each positive disorder on a three-level ordinal scale: minimal (little to no impairment), moderate (difficulties in daily life tasks), or severe (unable to perform essential daily tasks). To avoid false positive diagnoses, we diagnosed major depression only if it was associated with severe impairment. This is consistent with prior research (13) and comparable to what we did at prior assessments. Because there is not a similar precedent for bipolar disorder, we adopted a less stringent approach and made the diagnosis only when symptoms were associated with at least moderate impairment.

Persistent ADHD was defined as meeting full or subthreshold criteria for DSM-IV ADHD during the interval between the 5-year and 11-year assessments. Participants were defined as having subthreshold ADHD if they endorsed more than half of, but less than full, diagnostic criteria (i.e., four or five ADHD symptoms) but met all other diagnostic requirements (e.g., age at onset). Socioeconomic status was measured with the 5-point Hollingshead scale (14). To measure overall lifetime functioning, we used the DSM-IV Global Assessment of Functioning Scale (GAF) (12).

Analyses of demographic factors relied on Pearson chi-square tests and t tests for binary and dimensional variables, respectively. We examined psychopathology throughout the lifespan and within the past year (1-year prevalence), using a three-pronged strategy to avoid the inflated type I error rate that could result from multiple statistical testing. First, to decrease the initial number of tests, we aggregated diagnostic outcomes into composite categories: mood disorders comprised major depression and bipolar disorder; anxiety disorders comprised separation anxiety, panic disorder, agoraphobia, specific phobia, social phobia, generalized anxiety disorder, and obsessive-compulsive disorder (separation anxiety was not included in the analysis of 1-year outcomes); antisocial disorders comprised conduct disorder, oppositional defiant disorder, and antisocial personality disorder; developmental disorders comprised enuresis, encopresis, language disorder, and Tourette's/tic disorders (developmental disorders were not included in the analysis of 1-year prevalences); substance dependence comprised alcohol dependence, drug dependence, and nicotine dependence; and eating disorders comprised full or subthreshold anorexia nervosa and bulimia nervosa. These summary disorders were coded positive if any of the constituent diagnoses were endorsed, and negative otherwise.

Second, we conducted a set of six tests (the six composite diagnostic categories) that each compared the ADHD and comparison groups using Holm's sequential Bonferroni method (15) to correct for multiple testing and maintain a family-wise error rate of 0.05. Third, for any composite category that was significant, we tested each of the constituent diagnoses using Holm's method.

To estimate the lifetime prevalence of psychopathology, we used Cox proportional hazards survival models. For each disorder, lifetime history of any disorder was defined as positive if a positive response was given at any assessment (baseline, 5-year follow-up, or 11-year follow-up). These models used all available data for each participant, including those not assessed at the 11-year follow-up; thus, all 262 girls are included. We used the earliest age at onset in computing the survival time for case subjects and the age at the most recent interview as the time of censoring for noncase subjects. To estimate cumulative prevalence, we calculated Kaplan-Meier morbidity risks in the ADHD and comparison groups up to age 22 (the mean age of the sample). For the 1-year prevalence analysis, we used logistic regression to compare the ADHD and comparison groups. One-year prevalence was defined as positive if the participant met criteria for a given disorder in the year prior to the 11-year follow-up.

Of the 140 girls with ADHD and 122 comparison girls recruited at baseline, 96 (69%) and 91 (75%), respectively, were reassessed at the 11-year follow-up. The follow-up rate did not differ between the groups. There were no significant differences between girls successfully followed up and those lost to follow-up on socioeconomic status, age, race, GAF score, familial intactness, ascertainment source, or psychiatric outcomes (Table 1). At the 11-year follow-up, girls in the ADHD group were on average 1 year younger than comparison girls (Table 2). Survival models for lifetime disorders accounted for this difference in age, and age was used as a covariate in logistic regression models of 1-year prevalence. At the 11-year follow-up, 93% of the girls in the ADHD group had received some form of treatment for ADHD during their lives; 1% received counseling alone (N=1), 21% received medication alone (N=20), and 71% (N=68) received both counseling and medication. During the 1-year period before the 11-year follow-up assessment, 42% were receiving some form of treatment for the disorder; 17% (N=16) were receiving medication alone and 25% (N=24) were receiving both counseling and medication. Among the 96 girls in the ADHD group reascertained at the 11-year follow-up, the rate of full or subthreshold ADHD during the interval between the year 5 and year 11 assessments was 69% (N=66), and the rate of current (i.e., in the past month) full or subthreshold DSM-IV ADHD was 62% (N=60).

The risks for all six composite lifetime diagnostic categories were higher in the ADHD group than in the comparison group; hazard ratios were 6.8 (95% CI=3.7–12.6) for mood disorders, 2.1 (95% CI=1.6–2.9) for anxiety disorders, 7.2 (95% CI=4.0–12.7) for antisocial disorders, 3.2 (95% CI=2.0–5.3) for developmental disorders, 2.7 (95% CI=1.6–4.3) for substance dependence disorders, and 3.5 (95% CI=1.6–7.3) for eating disorders (Figure 1). All six composite categories remained statistically significant after controlling for baseline psychopathology for each of the other four categories.

ADHD girls had significantly higher lifetime prevalences of major depression, bipolar disorder, separation anxiety disorder, agoraphobia, social phobia, specific phobia, panic disorder, generalized anxiety disorder, oppositional defiant disorder, conduct disorder, antisocial personality disorder, Tourette's/tic disorders, language disorder, enuresis, encopresis, nicotine dependence, alcohol dependence, drug dependence, and bulimia nervosa (Table 3). However, when we corrected for other baseline psychopathology, the lifetime risks for encopresis, nicotine dependence, alcohol dependence, and drug dependence lost statistical significance.

The ADHD group had significantly higher 1-year prevalences of composite mood, anxiety, antisocial, and substance dependence disorders relative to the comparison group (Table 4). The 1-year prevalence of eating disorders was not significantly different between the ADHD and comparison groups (7% versus 3%, z=1.07, p=0.29). Except for substance dependence disorders (p=0.07), significant findings remained significant after controlling for all baseline psychopathology (i.e., baseline mood, anxiety, and antisocial disorders), including the baseline status of the disorder predicted at follow-up. Corrections for baseline psychopathology in this latter analysis did not include eating disorders or substance dependence at baseline because they were rare at baseline (N=5 and N=9, respectively).

Similar findings were observed for 1-year rates of individual disorders. The rates of major depression, agoraphobia, social phobia, oppositional defiant disorder, and nicotine dependence were higher in the ADHD group relative to the comparison group (Table 4). However, when findings were adjusted for baseline psychopathology (including the baseline status of the disorder predicted at follow-up), only agoraphobia remained statistically significant (p<0.001). The 1-year prevalences of composite psychiatric disorders were not associated with lifetime or 1-year medication use for ADHD.