Recent Clinical Findings From Longitudinal Studies

June 1, 2008

There is substantial comorbidity with oppositional defiant disorder (ODD) and conduct disorder (CD) in children with attention-deficit/hyperactivity disorder (ADHD). It is important to determine the effect of comorbid ODD and CD on the clinical course in youth with ADHD. Biederman and associates1 recently published clinical findings from a 10-year prospective, longitudinal study of boys with ADHD, following them into early adulthood.

Comorbidity and course of ADHD

There is substantial comorbidity with oppositional defiant disorder (ODD) and conduct disorder (CD) in children with attention-deficit/hyperactivity disorder (ADHD). It is important to determine the effect of comorbid ODD and CD on the clinical course in youth with ADHD. Biederman and associates1 recently published clinical findings from a 10-year prospective, longitudinal study of boys with ADHD, following them into early adulthood.

At the start of the study, there were 140 boys with ADHD and a control group of 120 boys without ADHD. The study population was obtained from pediatric and psychiatric clinics. Participants were assessed at 1-year, 4-year, and 10-year follow-up. Retention in the study was good, with 112 patients (80%) in the ADHD group and 105 patients (88%) in the control group assessed at 10-year follow-up. The mean age of patients was 11 years at baseline.

Age at onset of ODD and CD was earlier in boys with ADHD: the mean age at onset of ODD was 5 years compared with 10 years in the control group; the mean age at onset of CD was 9 years in boys with ADHD compared with 14 years in the control group.

It was found that in youths with ADHD and ODD, the risk of ODD and major depressive disorder increased significantly at 10-year follow-up. In youths with ADHD and ODD and CD, the risk of psychoactive substance use disorders (alcohol and drug abuse or dependence) and bipolar disorder increased significantly at 10-year follow-up. Increased risk of CD and antisocial personality disorder was found in both groups; however, the risk was significantly higher in those who had ODD and CD than in those with ODD alone.

The youths with ADHD and ODD and CD were significantly more likely to be expelled from school, be convicted of a crime, or be fired from a job by 10-year follow-up. These youths were also likely to have had sex before 16 years. Increased risk of moving violations was found in the ADHD alone and in the ADHD with ODD and CD groups compared with the control group. Interestingly, ADHD in the absence of ODD or CD did not predict antisocial outcomes; however, the investigators recommended caution in interpreting this result because the sample size for ADHD alone was small.

Based on these findings, it was estimated that ODD would persist in 11% of the adolescents with ADHD and ODD by age 25. In the group of adolescents with ADHD and ODD and CD it was estimated that 33% would continue to have ODD at age 25.

The authors concluded that in boys with ADHD, the clinical course varies depending on whether they have comorbid ODD or comorbid ODD and CD. In the long term, there were significantly more adverse consequences for youths with ADHD who had both ODD and CD; ODD was more persistent in this group. There was greater psychiatric morbidity and adverse psychosocial sequelae with the presence of CD. The authors noted that CD and not ODD results in significant adverse outcomes for youth with ADHD and comorbid ODD and CD. In addition, ODD alone increases the long-term risk of major depression.

Executive function deficits in ADHD

A longitudinal study of youths with ADHD was conducted to determine whether executive function deficits persist into young adulthood.2 A sample of 85 males aged 9 to 22 years with ADHD was followed over years into young adulthood. The mean age of patients at the first neuropsychological assessment was 14 years. At follow-up, the mean age of these patients was 21 years, with a range of 16 to 30 years. The mean time from the first assessment to the follow-up assessment was 7 years.

Assessments of neuropsychological functioning included measures of sustained attention/vigilance, organization and planning, interference control, response inhibition, set shifting and categorization, selective attention and visual scanning, verbal and visual learning, and memory. Executive function deficits were considered to be present in those who had impairment in 2 or more of these neuropsychological measures, which was defined as 1.5 standard deviations from the mean of the controls' scores.

It was found that 69% of the adolescents with executive function deficits at first assessment had such deficits at the 7-year follow-up. Forty- four of 59 patients (75%) without executive function deficits at first assessment did not have deficits at the 7-year follow-up. Therefore, the investigators concluded that executive function deficits are relatively stable in youths with ADHD. These results have important implications for early intervention to reduce the likelihood of future academic or occupational problems.

Early indicators of bipolar disorder

The results from a longitudinal study designed to identify earlier indicators of bipolar disorder were recently reported.3 The study sample consisted of high-risk offspring (n = 127) from families in which 1 parent had a diagnosis of bipolar disorder. The comparison group consisted of offspring (n = 61) of parents with no psychi- atric diagnosis.

The mean age at first assessment was approximately 16 years; the mean age at last assessment was 20 years in high-risk offspring. The mean length of follow-up was about 4 years, with an upper range of 9 years. A significant finding from the study was that high-risk offspring who had no psychiatric disorders in childhood or mid-adolescence remained well at the follow-up assessment. In adolescents who had a previous diagnosis of depression, 33% (3 of 9) met criteria for bipolar disorder at follow-up assessment. Antecedent anxiety and sleep disorders also increased the likelihood of a subsequent mood disorder. Of 40 offspring with anxiety and/or sleep disorders, 12 had subsequent bipolar disorder and 12 had a depressive disorder. Only offspring of parents whose illness did not respond to lithium had elevated rates of antecedent ADHD before a diagnosis of bipolar disorder.

At the time of follow-up assessment, 26 (21%) high-risk offspring met criteria for bipolar spectrum disorder. In the majority of cases (81%), the index episode was depression. The mean age at onset of the index mood episode was 15 years. In those offspring who had an index episode of depression, there was a mean interval of 3 years before the first manic or hypomanic episode, although the range was wide, from 1 to 13 years.