Elsevier

Biological Psychiatry

Volume 48, Issue 11, 1 December 2000, Pages 1037-1044
Biological Psychiatry

Original article
Parsing the association between bipolar, conduct, and substance use disorders: a familial risk analysis

https://doi.org/10.1016/S0006-3223(00)00906-9Get rights and content

Abstract

Background: Bipolar disorder has emerged as a risk factor for substance use disorders (alcohol or drug abuse or dependence) in youth; however, the association between bipolar disorder and substance use disorders is complicated by comorbidity with conduct disorder. We used familial risk analysis to disentangle the association between the three disorders.

Methods: We compared relatives of four proband groups: 1) conduct disorder + bipolar disorder, 2) bipolar disorder without conduct disorder, 3) conduct disorder without bipolar disorder, and 4) control subjects without bipolar disorder or conduct disorder. All subjects were evaluated with structured diagnostic interviews. For the analysis of substance use disorders, Cox proportional hazard survival models were utilized to compare age-at-onset distributions.

Results: Bipolar disorder in probands was a risk factor for both drug and alcohol addiction in relatives, independent of conduct disorder in probands, which was a risk factor for alcohol dependence in relatives independent of bipolar disorder in probands, but not for drug dependence. The effects of bipolar disorder and conduct disorder in probands combined additively to predict the risk for substance use disorders in relatives.

Conclusions: The combination of conduct disorder + bipolar disorder in youth predicts especially high rates of substance use disorders in relatives. These findings support previous results documenting that when bipolar disorder and conduct disorder occur comorbidly, both are validly diagnosed disorders.

Introduction

In recent years, a focus on bipolar disorder (BPD) as a risk factor for substance use disorders (SUDs; alcohol or drug abuse or dependence) in youth has emerged as a clinical and public health concern. A prospective study of children and adolescents with and without attention-deficit/hyperactivity disorder (ADHD) found that early-onset BPD predicted subsequent SUD independently of ADHD (Biederman et al 1997). Similarly, an excess of SUDs has been reported in studies of adolescents with BPD or prominent mood lability and dyscontrol (Biederman et al 1997, West et al 1996, Wilens et al 1997a, Wills et al 1995, Young et al 1995. West et al (1996) reported that 40% of inpatient adolescents with BPD suffered from SUDs. Likewise, we reported that psychiatrically referred adolescent outpatients with SUDs were more likely than those without SUDs to have comorbid BPD (Wilens et al 1997a).

But understanding the association between BPD and SUDs is complicated by the fact that BPD is frequently comorbid with conduct disorder (CD; Biederman et al 1998b, Faraone et al 1997b, Geller et al 1994, Kovacs and Pollock 1995, Kutcher et al 1989, Wozniak et al 1995a) and CD is a well-documented risk factor for SUDs in youth Bukstein et al 1989, Bukstein et al 1992, DeMilio 1989, Hovens et al 1994, Kaminer 1991, McKay et al 1991, McKay et al 1992, West et al 1996, Wilens et al 1997a.

One approach to addressing this issue is the use of data from families (Faraone et al 1999). Since BPD, CD, and SUD are known to be familial conditions, examining their familial patterns of aggregation and coaggregation can disentangle the associations among them. Although several studies have shown a familial association between BPD and SUD and between CD and SUD Dunner et al 1979, Maier and Merikangas 1996, Morrison 1975, Penick et al 1978, Raskin and Miller 1993, no studies examined the three-way associations between BPD, CD, and SUD.

A better understanding of the links among SUDs, CD, and BPD is of high scientific, clinical, and public health relevance. Clinically, the identification of BPD in SUD youth may permit the use of appropriate treatments targeting the underlying mood disorder. Scientifically, the delineation of a subtype of SUDs linked to mood disorders in the young may lead to the identification of a more homogeneous subgroup of SUD youth with distinct pathophysiology, course, family history, outcome, and treatment response. Considering the extreme severity of juvenile BPD, its co-occurrence with SUDs seriously complicates an already compromised life situation. Moreover, if some of the antisocial behaviors of youth with BPD and CD can be attributed to BPD, this might identify a subset of youth that could be triaged out of the juvenile justice system.

The purpose of this study was to disentangle the association between BPD, CD, and SUD using familial risk analysis (Faraone et al 1999). We tested three hypotheses: 1) BPD in probands is a risk factor for SUD in relatives, independent of comorbid CD in probands; 2) CD in probands is a risk factor for SUD in relatives, independent of comorbid BPD in the probands; and 3) in comorbid cases, the effects of BPD and CD in probands combine additively to predict the risk for SUDs in relatives (i.e., relatives in the comorbid proband group are at greatest risk for SUDs, but no more than what we would expect from the risks imparted by the individual disorders in the probands).

Section snippets

Subjects

We pooled data from two samples of youth with DSM-III-R BPD and their first-degree relatives. The first sample comprised 29 youths with BPD and their 99 first-degree relatives ascertained through a longitudinal study of ADHD that had assessed 128 ADHD probands and their 434 relatives as well as 107 non-ADHD probands (control subjects) and their 354 relatives Biederman et al 1996, Faraone et al 1997a. The second sample comprised 16 consecutively referred BPD children and their 46 first-degree

Sociodemographic characteristics

Table 1shows the sociodemographic characteristics of the sample. The mean ages of probands with CD+BPD (13.3 years) and probands with BPD (10.9 years) were significantly lower than those of the CD probands and control subjects (16.6 and 15.3 years, respectively). Consequently, the mean age of parents of CD+BPD probands (39.2 years) was significantly lower than the mean age of parents of the control probands (42.2 years). Also, the mean ages of the siblings of probands with CD+BPD (14.2 years)

Discussion

Using familial risk analysis we examined the three-way association between CD, BPD, and SUD. We found strong support for hypothesis one: after accounting for CD in probands, BPD in probands was a risk factor for SUDs in relatives, including both drug and alcohol addiction. We found weaker support for hypothesis two: after accounting for BPD in probands, CD in probands was a risk factor for alcohol dependence in relatives but not for drug dependence, independent of comorbid BPD in the probands.

Acknowledgements

This work was supported in part by Grants No. ROIMH57934-01 (SVF) and No. ROI MH41314-07 (JB) from the National Institute of Mental Health, Bethesda, Maryland.

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