Further evidence of an association between adolescent bipolar disorder with smoking and substance use disorders: A controlled study

Abstract

Although previous work suggests that juvenile onset bipolar disorder increases risk for substance use disorders and cigarette smoking, the literature on the subject is limited. We evaluated the association of risk for substance use disorders and cigarette smoking with bipolar disorder in adolescents in a case–control study of adolescents with bipolar disorder (n = 105, age 13.6 ± 2.5 years [mean]; 70% male) and without bipolar disorder (“controls”; n = 98, age 13.7 ± 2.1 years; 60% male). Rates of substance use and other disorders were assessed with structured interviews (KSADS-E for subjects younger than 18, SCID for 18-year-old subjects). Bipolar disorder was associated with a significant age-adjusted risk for any substance use disorder (hazard ratio[95% confidence interval] = 8.68[3.02 25.0], χ² = 16.06, p < 0.001, df = 1), alcohol abuse (7.66 [2.20 26.7], χ² = 10.2, p = 0.001, df = 1), drug abuse (18.5 [2.46 139.10], χ² = 8.03, p = 0.005, df = 1) and dependence (12.1 [1.54 95.50], χ² = 5.61, p = 0.02, df = 1), and cigarette smoking (12.3 [2.83 53.69], χ² = 11.2, p < 0.001, df = 1), independently of attention deficit/hyperactivity disorder, multiple anxiety, and conduct disorder (CD). The primary predictor of substance use disorders in bipolar youth was older age (BPD − SUD versus BPD + SUD, logistic regression: χ² = 89.37, p < 0.001). Adolescent bipolar disorder is a significant risk factor for substance use disorders and cigarette smoking, independent of psychiatric comorbidity. Clinicians should carefully screen adolescents with bipolar disorder for substance and cigarette use.

Introduction

A growing literature documents that many seriously disturbed children are afflicted with bipolar disorder (BPD) (Birmaher and Axelson, 2006). Juvenile BPD in its various forms affects from 1 to 4% of pediatric groups (Lewinsohn et al., 1995) with up to one-fifth of psychiatrically referred children and adolescent psychiatric outpatients manifesting BPD (Weller et al., 1986, Wozniak et al., 1995). The literature also documents the concurrent, face, and predictive validity of BPD in childhood (Biederman et al., 2003). Recent work suggests that pediatric onset BPD may represent a unique developmental type of BPD characterized by a chronic course, mixed presentations, and high levels of severe irritability (Carlson, 1984, Wozniak et al., 1995, Biederman et al., 2003, Geller et al., 2004, Axelson et al., 2006, Birmaher and Axelson, 2006, Birmaher et al., 2006, Geller et al., 2006). For instance, two ongoing multisite, National Institute of Mental Health (NIMH) funded studies show that children and adolescents with BPD maintain a functionally impaired status characterized by a highly relapsing and remitting course (Birmaher, 2004, Geller et al., 2004, Birmaher et al., 2006, Geller et al., 2006). BPD is a substantial cause of psychiatric morbidity among youth including high rates of hospitalization, disruption of the family environment, and psychosocial disability (Akiskal et al., 1985, Wozniak et al., 1993, Weller et al., 1995, West et al., 1996, Geller et al., 2002a, Geller et al., 2002b, Birmaher and Axelson, 2006).

Systematic studies of BPD children have found high rates of attention deficit/hyperactivity disorder (ADHD), anxiety disorders (panic, and obsessive-compulsive disorder) (Strober et al., 1998, Geller et al., 1995, Wozniak et al., 1995, West et al., 1996, Geller et al., 1998a, Geller et al., 1998b, Geller et al., 2000, Geller et al., 2006), and conduct disorder (CD) (Geller et al., 1995, Kovacs and Pollock, 1995, Biederman et al., 1997a, Carlson et al., 1998, Geller et al., 2000). Among the most concerning comorbidities in juvenile onset BPD is the link with cigarette smoking and substance use disorders (SUD; including drug or alcohol abuse or dependence). Recent epidemiological data suggests that SUD occurs in up to 15% of the adult population (Kessler et al., 2005) with a 1-year prevalence of 1.4% and 0.6% for drug abuse and dependence (Compton et al., 2007); and 4.7% and 3.8% for alcohol abuse and dependence (Grant et al., 2004). These data also show the frequent onset of both alcohol and drug use disorders during adolescence (Grant et al., 2004, Kessler et al., 2005, Compton et al., 2007).

Emerging data suggest a bi-directional over-representation of BPD and SUD across the lifecycle. About half of referred and community samples of adults with BPD have a lifetime history of SUD (Reich et al., 1974, Himmelhoch, 1979, Winokur et al., 1995, Strakowski et al., 1998, Merikangas et al., 2007). Likewise, an excess of BPD has also been reported in SUD samples (Rounsaville et al., 1982, Gawin and Kleber, 1986, Weiss et al., 1988, Regier et al., 1990, Rounsaville et al., 1991). Data from studies of BPD adults also suggest that the risk for SUD is particularly high in those adults who had the onset of their BPD prior to age 18 years (Dunner and Feinman, 1995, Perlis et al., 2004, Fleck et al., 2006, Goldstein and Levitt, 2006, Lin et al., 2006). For instance, Lin et al. (2006) showed that earlier onset BPD was associated with a higher risk for SUD in adults than later onset (e.g. adult onset) BPD. Similarly, McElroy and colleagues showed an association between early onset BPD, mixed mood symptoms and SUD (McElroy et al., 2001).

A limited literature exists suggesting that juvenile onset BPD may be a major risk factor for SUD. For instance, an excess of SUD has been reported in adolescents with BPD (Wills et al., 1995, Young et al., 1995, West et al., 1996, Biederman et al., 1997a, Wilens et al., 1997a, Wilens et al., 2004, Birmaher and Axelson, 2006) and BPD appears over-represented in youth with SUD (Wills et al., 1995, Young et al., 1995, West et al., 1996, Wilens et al., 1997a, Wilens et al., 1997b, Biederman et al., 1997b, Weinberg and Glantz, 1999, Deas and Brown, 2006). However, the lack of controls, retrospective nature of the adult studies, and small sample sizes in some of these studies limits their interpretabilty.

One important potential confound in disentangling the relationship of BPD and SUD is psychiatric comorbidity. One of the most frequent comorbidities in BPD is conduct disorder (CD) (Kovacs and Pollock, 1995, Wozniak et al., 1995, Faraone et al., 1997) (Birmaher and Axelson, 2006). Since CD is a well-known risk factor for early onset SUD (Tarter et al., 1990, Brook et al., 1995, Whitmore et al., 1997, Carlson et al., 1998), a thorough examination of putative associations between BPD and SUD requires careful evaluation of the influence of comorbid CD. For instance, while some work has suggested that CD accounts for SUD in BPD adults (Carlson et al., 1998) we previously reported that the association between BPD and SUD in youth was independent of CD (Wilens et al., 1999). Another potential confounder in evaluating SUD risk in BPD is ADHD. High rates of ADHD have consistently been reported in samples of children and adolescents with BPD (Wozniak et al., 1995, Geller et al., 2002a, Geller et al., 2002b); and ADHD has been reported to be a risk factor for SUD in young adults (Wilens et al., 1997a, Molina and Pelham, 2001). Similarly, anxiety disorders within BPD have also been reported to be linked independently to an elevated risk for SUD (Dilsaver et al., 2006). Examination of specific psychiatric comorbidities in the manifestation of SUD will provide useful information as to the contribution of BPD itself and potential mechanism(s) of SUD risk.

Characterizing the risk and nature of the relationship between BPD and SUD in the young is of particular clinical scientific and public health importance. BPD is an increasingly recognized prevalent and persistent disorder affecting children and adolescence (Weller et al., 1995, Wozniak et al., 1995, Geller and Luby, 1997, Brady et al., 1998, Geller et al., 1998a, Geller et al., 1998b, Geller et al., 2004, Birmaher et al., 2006), that commonly onsets prior to SUD (Stowell and Estroff, 1992, West et al., 1996, Biederman et al., 1997b, Wilens et al., 1999). Also, persistent BPD into adulthood is associated with SUD (Dunner and Feinman, 1995, Strakowski et al., 1998) and BPD is treatable (Pavuluri et al., 2004, Kowatch et al., 2005). Thus, efforts at improving the understanding of the nature of the association between BPD and SUD in the young can lead to further refinements in efforts aimed at mitigating this risk.

To this end, this study's main aim was to re-examine the association between BPD and SUD in adolescents. To this end we examined findings from an ongoing, controlled, longitudinal family-based study of adolescents with BPD attending to developmental factors, correlates of BPD, and psychiatric comorbidity. Based on our previous findings, we hypothesized that adolescents with BPD will be at higher risk for SUD than non-mood disordered adolescents, and that the association between BPD and SUD would be independent of psychiatric comorbidity with ADHD, conduct and multiple anxiety disorders.