The results of this follow-up (average 10 years) study of two cohorts of children to examine early predictors for later SUD partially support our hypotheses. Our results support the hypothesis that ADHD is a risk for later SUD and the major predictive importance of early CD on subsequent SUD in ADHD youth. However, we failed to demonstrate significant associations between familiality, baseline cognitive, non-CD psychiatric, treatment, subtype, or academic dysfunction and later SUD in our ADHD youth. Persistent ADHD was associated with later SUD. These longitudinal findings support and add to the literature the importance of ADHD as a risk factor for later cigarette smoking, drug, and alcohol use disorders.
Our findings support the hypothesis that ADHD itself is a risk for subsequent SUD. In our sample, ADHD was associated with both an earlier onset and a higher risk for SUD. These data support previous retrospective findings in adults with ADHD37
and prospective child studies.12, 14–18
For example, in 5- and 8-year follow-up studies, more alcohol use was shown among hyperactive and largely conduct disordered ADHD adolescents compared to non-ADHD controls.18
Molina et al.14
reported that comorbid disruptive symptoms and the severity of ADHD were associated specifically with increased SUD risk. Our data also show that when controlling for CD, ADHD continued to be significantly associated with SUD.
Our findings showing that CD with or without ADHD is a risk factor for SUD are well supported in the literature. For instance, Brook et al.5
and Crowley et al.38
have shown that independent of ADHD status, CD in children remains a major risk factor for subsequent SUD. Likewise, Mannuzza et al.12
have shown the importance of CD in ADHD and later SUD throughout adolescence and into adulthood. As part of the NY longitudinal study, Lampert and colleagues showed that delinquency in ADHD was related to SUD.39
Molina et al,17
as part of the multimodal treatment of ADHD three-year follow-up study reported that delinquent behavior in ADHD resulted in an increased risk for substance use. These aggregate studies are particularly noteworthy in that CD can be diagnosed early in life. In our sample, 30% of our Children with ADHD at their baseline assessment already manifested CD that subsequently increased their risk for SUD by almost three fold.
In the current data, we found that mood disorders predicted drug use disorders, but not overall SUD, alcohol use disorders, or cigarette smoking. These findings partially support our previous work in ADHD and controls in which major depression was not associated with SUD; yet, bipolar disorder was associated with SUD.13, 37, 40
Unlike our previous report that found a significant association between bipolar and SUD through the five-year follow-up of boys with ADHD,13
the current analysis used baseline data on combined mood disorders (due to our small sample size of bipolar subjects (N=26)) to predict later SUD. Emerging data strongly support the role of early bipolar disorder in later SUD41
Contrary to our hypothesis, we also failed to find significant associations between indices of academic underachievement or cognitive dysfunction and later SUD in our ADHD group. These findings are at odds with an older literature indicating the importance of academic achievement and later substance use.23
Likewise, some studies have shown that adults with SUD manifest cognitive dysfunction at higher rates than those without SUD;42, 43
however, the directionality of causality remains unclear. Our findings are consistent with other studies that largely show cognitive deficits to be directly related to the pernicious effects of SUD. For instance, a number of studies have shown impaired cognitive or neuropsychological functioning in individuals with ongoing SUD; these deficits normalized with the cessation of SUD,43, 44
suggesting that these subjects had normal executive functioning prior to the effects of the substances of abuse. Moreover, we have recently shown that neuropsychologically defined executive functioning deficits in midadolescence do not predict SUD five years later.45
While the discrepancies between our findings and those above are not clear, it may be that our classification of academic and cognitive functioning may not have been sensitive enough to examine more subtle effects on later SUD. Alternatively, it may be that ADHD itself creates a risk factor for SUD that exceeds that of further academic and cognitive dysfunction (ceiling effect) or that neuropsychological/executive functioning deficits are not causal, but more a result of SUD.
We did not find that the subtype of ADHD nor ADHD symptom count predicted later SUD. However, we did find that the persistence of ADHD (e.g. presence of ADHD at 10 year follow-up) was associated with a robust 3 fold increased risk for SUD. Our findings are similar to Molina et al 14
, who as part of a longitudinal study reported that persistent ADHD was associated with later SUD. We failed to find that medication (largely stimulant) or psychotherapy at baseline predicated SUD at the 10 year follow-up. These findings from this combined sample of males and females with ADHD extend previous findings in the 10 year sample of males 46
in which we reported no increase or decrease in SUD associated with stimulant treatment.16
As we previously speculated, the lack of protective effects of treatment on later SUD previously reported in mid adolescence 47, 48
may be related to the sample maturing through the age of risk for SUD, the inconsistent use of treatment (as evidenced by ADHD symptoms at follow-up related to SUD), offspring individuation and loss of parental monitoring, familial link of ADHD and SUD 49
, or the combination. Further studies examining the developmental influence of treatment, treatment persistence and adequacy on later SUD is necessary.
As we have reported previously,49
we found higher rates of SUD in our ADHD families. However, among children with ADHD, family history of SUD was not a predictor of subsequent SUD. While a rich literature has demonstrated the familial nature of SUD,50
and that familial SUD is associated with early onset SUD in offspring,51–53
the current findings showed no effects of familial SUD on the development of SUD within ADHD. Although the reasons for this finding remain unclear, it may be that in our middle class sample, parents with SUD histories were sensitive to substance use and monitored emergent SUDs in their offspring. It may also be that ADHD and related comorbidity created a ceiling effect for the development of SUD, limiting the additive effects of family history. Alternatively, it may be that while providing follow-up of 10 to 11 years, our group of ADHD at a mean age of 20.38 ± 4.55 years is still not fully through the age of risk for SUD in ADHD.37
We also found that familial ADHD did not increase the risk for subsequent SUD. In fact, we found familial ADHD offered a protective effect against subsequent alcohol use disorder in our ADHD youth. Our findings are noteworthy given that we have previously shown that ADHD is linked to SUD in families.49
Our findings may be related to ADHD parents being attentive to the diagnosis and treatment of ADHD (and SUD) in their offspring. For instance, in these samples at 4- to 5-year follow-up, we have previously shown that treatment of ADHD may reduce or delay the onset of both cigarette smoking54
in adolescence. The aggregate family findings are reassuring in that neither ADHD nor SUD in a family member consistently increase the risk for SUD, although in the current study, we only examined baseline predictors of subsequent SUD.
Results from the current data have important clinical relevance when assessing subsequent SUD risk in children with a mean age of 11 years. For instance, children with ADHD, and in particular, those with comorbid CD, require enhanced monitoring for SUD and its antecedents. Family histories of either ADHD or SUD do not increase the risk for subsequent SUD. Similarly, ADHD subtype, social, cognitive, and academic dysfunction in Children with ADHD do not appear to further increase the risk for SUD. While early treatment of ADHD does not increase or decrease later SUD, persistent ADHD is associated with a substantially increased risk for SUD. Education for families of children with ADHD can help focus surveillance and early intervention that may reduce the subsequent development of SUD.
There are a number of methodological limitations to the current study. We utilized self and parent reports by structured interview for SUD instead of objective testing. We have previously shown that structured interview reports appear more sensitive and specific for establishing SUD in this population compared to urine toxicological testing.55
We may have missed important interval events as we were focused on examining baseline and subsequent SUD at the 10- to 11-year follow-up. Future studies should examine both moderators and mediators of subsequent SUD. Our sample of subjects with SUDs was relatively small, thereby limiting our power for sub-analyses and ability to adequately control for confounders. We chose not to control for multiple comparisons. Using the Bonferroni adjustment alters the statistical inference of a study from the testing of a number of specific hypotheses to a test of the universal null hypotheses.56, 57
This method increases the Type II error rate56, 57
and raises the issue of the amount of tests to be included in the adjustment.56
Our ADHD sample available for follow-up was largely middle class and Caucasian, thus limiting the generalization. Our sample at follow-up may not have been through the full age of risk for SUD.
Despite these limitations, our findings replicate previous work, highlighting that childhood ADHD is a risk factor for SUD, and CD within ADHD continues to be a very important determinant of subsequent SUD. Future studies examining the pathway to SUD in this age group and older samples are necessary to shed more light on potential mechanisms of SUD development in ADHD.