To our knowledge, this is the largest study to date examining SUD among adolescents with BP spectrum disorders, and the first to examine with adequate power the association of SUD with psychiatric comorbidities and the putative sequelae of SUD in this population. The lifetime prevalence of SUD among adolescents with BP was 16%, and did not differ significantly based on whether these adolescents experienced onset of BP in childhood or adolescence. Subjects with SUD were significantly older as compared to subjects without SUD. The most common substance of abuse/dependence was cannabis, followed by alcohol.
Compared to subjects without SUD, those with SUD were significantly less likely to be living with both biological parents. They had greater lifetime prevalence of suicide attempts and of sexual and physical abuse, although the latter findings were reduced to statistical trends after controlling for confounders. Twelve-month prevalence of self-reported trouble with police was significantly greater among subjects with SUD, and females with SUD were significantly more likely to report past-year pregnancy and abortion as compared to females without SUD (although this was reduced to a statistical trend in regression analyses). There were no significant between-group differences in lifetime prevalence of any other clinical characteristics or comorbidities, or in family history.
The finding of zero prevalence of SUD among children in the COBY study converges with previous findings (23
). The prevalence of SUD (16%) among adolescents with BP was in keeping with some previous studies (6
), but lower than that of other studies (8
). A study of adolescents hospitalized for mania reported a 39% prevalence of SUD (25
), whereas figures in outpatient samples have ranged from 18% to 32% (8
). The somewhat lower prevalence of SUD in the present study as compared to the 22% reported in a community sample of 14-18 year olds with BP (6
) may be explained by the older mean age in that study (16.6 vs 15.2 years). Given that few adolescents in COBY (19%) were inpatients at the time of referral, the higher prevalence of SUD in the study of adolescents hospitalized for mania could also be expected (25
The prevalence of SUD among adolescents in this study did not differ based on whether BP onset occurred in childhood or adolescence, contrary to two previous studies (8
). This discrepancy may relate to differences in ascertainment. Whereas COBY was designed to examine BP specifically, one previous study was derived from a sample originally recruited based on a diagnosis of ADHD (9
). Another study that specifically recruited BP subjects (8
) did not control for age, which may have confounded the results. Present findings are convergent with retrospective data from adults with BP which indicate that child-onset and adolescent-onset BP confer greater risk of SUD as compared to adult-onset BP, but that adolescent-onset BP does not confer greater risk of SUD compared to child-onset BP (26
One possible explanation for the differences between present and previous findings is that subjects with BP-II and BP-NOS were included in this study, whereas most previous studies include only subjects with BP-I. However, analyses were recalculated for BP-I subjects only, and both the prevalence and correlates of SUD were nearly identical to the findings for the combined sample. It is unlikely, therefore, that this methodologic difference accounts for these findings.
Only half of the SUD group (8% overall) demonstrated alcohol abuse/dependence. These findings contrast those of adults, among whom alcohol is the most common substance of abuse/dependence (1
), but converge with previous findings for adolescents (6
). Findings from epidemiologic studies suggest that drug abuse/dependence is more common than alcohol abuse/dependence among adolescents with BP (6
), whereas alcohol abuse/dependence is more common among young adults with BP (28
). This observation is important for developmentally-appropriate prevention and intervention strategies.
As hypothesized, subjects with conduct disorder had significantly increased prevalence of SUD. Previous studies have found that conduct disorder is a risk factor for SUD among adolescents in general (29
), and that comorbid conduct disorder does not fully account for the association between SUD and BP among adolescents (8
). However, to our knowledge, this is the first study to demonstrate that conduct disorder is associated with significantly increased prevalence of SUD among adolescents with BP.
The hypothesis that subjects with SUD would have increased BP severity was only partially supported. Suicide attempts were significantly more prevalent among subjects with versus without SUD. Ample literature attests to the increased rate of suicidality among youth with SUD (30
). Similarly, previous studies have shown that SUD is a significant risk factor for suicide attempts among adults with BP (4
). BP has been implicated as a putative risk factor for suicide among adolescents, and SUD is twice as common among suicide completers as compared to ideators/attempters (32
). A previous study based on the COBY study reported that the lifetime prevalence of SUD was 17% among attempters and 5% among non-attempters (19
). BP adolescents with SUD may be at increased risk for suicide attempts, as is the case among adults.
The presence of SUD was significantly associated with trouble with police, and this finding persisted after adjusting for the high prevalence of CD. These findings replicate those in studies of adults (5
). In a previous study of youth with comorbid BP (or MDD and BP predictors) and SUD, 52% reported a lifetime history of arrest (34
). Present findings demonstrate that conduct disorder does not confound the association between SUD and trouble with police. Albeit that legal difficulty may in some cases be a direct consequence of underage drinking, or of possession or distribution of illicit substances, it is important to consider that legal difficulty is a common proximal risk factor preceding adolescent suicide (35
SUD among females was associated with greater 12-month prevalence of pregnancy and abortion. Substance use among adolescent females has previously been associated with risky sexual behavior and adverse sexual/reproductive outcomes, especially when depression is present (13
). Adolescent females with BP and SUD may be at risk for these outcomes as well.
The absence of significant between-group differences in family history in the present study converges with findings from adults (39
) and youth (34
) with BP. The prevalence of comorbid mania and SUD among any first-degree relative was nearly two-fold greater among BP adolescents with SUD as compared to BP adolescents without SUD. Although this difference did not reach statistical significance, it does replicate the finding by Winokur and colleagues showing a trend toward increased alcoholism among BP relatives of BP probands with alcoholism as compared to BP relatives of non-alcoholic BP probands (39
). When BP-I subjects were analyzed separately, between-group differences in family history of mania and comorbid mania and SUD attained statistical significance. Future studies examining the contribution of BP-subtype to family history variables associated with proband SUD are indicated.
The methodologic limitations of this study must be considered when interpreting these findings. First, under-reporting of SUD may have occurred. Although adolescent subjects were interviewed separately from parents, at least one parent was closely involved in this study which may have lead to under-reporting of SUD. Urine toxicology was not collected to address possible duplicity. Such false negative cases would serve to diminish the between-group differences examined, and this may have decreased the apparent impact of SUD on youth with BP. Second, this naturalistic study did not examine certain treatment-related details such as dosage and adherence, and did not systematically collect data regarding SUD treatment. Third, this study focused on the association between lifetime SUD and other lifetime variables (e.g., hospitalization, suicidality), and therefore present findings likely under-estimate the impact of concurrent SUD on BD severity. Fourth, trouble with police was ascertained via self-report, and details regarding the nature of or reason for this trouble could not be determined. Finally, this study employed cross-sectional and retrospective methodology. As such, it could not be determined whether SUD onset antecedent or consequent to physical/sexual abuse and/or not living with both parents. Although these variables are considered here as putative risk factors for SUD, the direction of causality is uncertain as SUD could also potentially predispose to sexual/physical abuse and/or not living with both parents. Similarly, temporal priority of SUD with suicide attempts or hospitalizations could not be determined.
Despite the acknowledged limitations, the results of the present study may have important clinical implications. Adolescents with comorbid BP and SUD have an elevated risk of suicide attempts, trouble with police, and teenage pregnancy and abortion. These risks exceed what would be expected from other predictors such as conduct disorder and non-intact families. Although these findings require replication, extreme vigilance is warranted in the monitoring and management of SUD among adolescents with BP. The finding of relatively low alcoholism as compared to adults with BP is important because clinical and epidemiologic data suggest that the prevalence of alcoholism among these adolescents will increase approximately 7-fold by middle-adulthood (1
). Clearly this presents an important opportunity for secondary prevention and early intervention that cannot be ignored. Future large-scale studies are needed to examine the dynamic relationship between substance use and BP among adolescents longitudinally, in order to elaborate on previous findings based on smaller sample sizes (42
). Reports examining these topics in the COBY sample will be forthcoming. Targeted preventative strategies for averting SUD among adolescents with BP are urgently needed.