and risk for suicide in youth has been previously reported by Brent et al. (1988), highlighting the long-held notion that bipolar disorder in youth is associated with not only high levels of morbidity but also mortality.

Lewinsohn, Klein, and Seeley (1995) studied 1,709 adolescents (14 to 18 years) randomly selected from nine senior high schools, representative of urban and rural districts in western Oregon. The lifetime prevalence of bipolar disorder (primarily bipolar disorder II and cyclothymia) was approximately 1.0%. An additional 5.7% of the sample reported experiencing a distinct period of abnormally elevated mood, expansive or irritable, although they never met the criteria for bipolar disorder per se. Both groups exhibited significant functional impairment and high rates of comorbidity (anxiety and disruptive behavior), suicide attempts, and mental health service utilization. The prevalence, age of onset, phenomenology, and course of bipolar disorder did not differ by gender. In a follow-up study, they found that less than 1.0% of adolescents with depression switched to bipolar disorder by age 24 (Lewinsohn, Rohde, Seeley, Klein, & Gotlib, 2000). The bipolar disorder and subsyndromal bipolar disorder subgroups both had elevated rates of antisocial and other personality symptoms. Both groups showed significant impairment in psychosocial functioning and had higher mental health treatment utilization. In general, adolescents with bipolar disorder showed significant continuity across developmental periods and adverse outcomes during young adulthood. Adolescent subsyndromal bi polar disorder was also associated with adverse outcomes in adulthood, but not with increased incidence of bipolar disorder, which questions the relationship of subsyndromal bipolar disorder in children and adolescents to true adulthood bipolar disorder.

A study from Bavaria, Germany, on a sample of 3,021 adolescents and young adults age 14 to 24 found a lifetime prevalence of 1.4% for bipolar I disorder and 0.4% for bipolar II disorder (Wittchen, Nelson, & Lachner, 1998). Ninety-four percent of the youth with either bipolar disorder considered themselves socially and economically impaired.

A 5-year follow-up of over 500 students of ages 20–24 years in Helsinki, Finland, found a 1-month prevalence rate of bipolar I of 0.2%. However, when bipolar II and bipolar-NOS were added, the prevalence rates were 0.9/100. In summary, the epidemiologic studies of adolescents and adults show an early age of onset of bipolar disorder and prevalence in adolescents close to what is found in studies of adults.

The symptomatic overlap of childhood mania with ADHD is one major source of diagnostic controversy. Rates of ADHD range from 60% to 90% in pediatric patients with mania (Borchardt & Bernstein, 1995; Geller et al., 1995; West, McElroy, Strakowski, Keck, & McConville, 1995;

Wozniak, Biederman, Kiely, et al., 1995). Although the rates of ADHD in samples of youth with mania are universally high, the age at onset modifies the risk for comorbid ADHD. For example, while Wozniak, Biederman, Kiely, et al. (1995) found that 90% of children with mania also had ADHD, West et al. (1995) reported that only 57% of adolescents with mania had comorbid ADHD. Examining further developmental aspects of pediatric mania, Faraone, Biederman, Wozniak, et al., (1997) found that adolescents with childhood-onset mania had the same rates of comorbid ADHD as manic children (90%), and that both these groups had higher rates of ADHD than adolescents with adolescent-onset mania (60%). Most recently, Sachs, Baldassano, Truman, & Guille (2000) reported that among adults with bipolar disorder, a history of comorbid ADHD was only evident in those subjects with onset of bipolar disorder before 19 years of age. The mean onset of bipolar disorder in those with a history of childhood ADHD was 12.1 years (Sachs et al., 2000). Similarly, Chang, Steiner, and Ketter (2000) studied the offspring of patients with bipolar disorder and found that 88% of manic children had comorbid ADHD and that the onset of mania in adults with bipolar disorder and a history of ADHD was 11.3 years of age. These findings suggest that age of onset of mania, rather than chronological age at presentation, may be the critical developmental variable that identifies a highly virulent form of the disorder that is heavily comorbid with ADHD.

Although ADHD has a much earlier onset than pediatric mania, the symptomatic and syndromatic overlap between pediatric mania and ADHD raises a fundamental question—namely, do children presenting with symptoms suggestive of mania and ADHD have ADHD, mania, or both? One method to address these uncertainties has been to examine the transmission of comorbid disorders in families (Faraone & Tsuang 1995; Faraone, Tsuang, & Tsuang, 1999). If ADHD and mania are associated because of shared familial etiologic factors, then family studies should find mania in families of ADHD patients and ADHD in families of manic patients. Studies that examined rates of ADHD among the offspring of adults with bipolar disorder all found higher rates of ADHD among these children than in controls (Faraone, Biederman, Mennin, & Russell, 1998).

Wozniak, Biederman, Mundy, et al. (1995) used familial risk analysis to examine the association between ADHD and mania within families of manic children. They found that relatives of children with mania were at high risk for ADHD that was indistinguishable from the risk in relatives of children with ADHD and no mania. However, mania and the comorbid condition of mania plus ADHD selectively aggregated among relatives of manic youth compared with those with ADHD and comparison children (Wozniak, Biederman, Mundy, et al., 1995). Almost identical findings were obtained in two independently defined family studies of ADHD probands with and without comorbid mania (Faraone, et al., 1998; Faraone, Biederman & Monuteaux, 2001). Taken together, this pattern of transmission in families suggests that mania in children might be a familiarly distinct subtype of either bipolar disorder or ADHD.

Like ADHD, CD is also strongly associated with pediatric mania. This has been observed separately in studies of children with CD, ADHD, and mania. Kovacs and Pollak (1995) reported a 69% rate of CD in a referred sample of manic youth and found that the presence of comorbid CD heralded a more complicated course of mania. Kutcher et al. (1989) found that 42% of hospitalized youths with mania had comorbid CD. The Zurich longitudinal study found that hypomanic cases had more disciplinary difficulties at school and more thefts during their juvenile years than did other children (Wicki & Angst, 1991). These reports are consistent with the well-documented comorbidity between CD and major depression (Angold and Costello 1993), because pediatric depression often presages mania (Geller, Fox, & Clark, 1994; Strober and Carlson, 1982). It is not surprising that mania and CD are also frequently comorbid.

Biederman et al. (1999) (Biederman, Faraone, Hatch, et al., 1997) investigated the overlap be

tween mania and CD in a consecutive sample of youth referred for treatment. They found a striking similarity in the features and age of onset of mania, regardless of comorbid CD. Whether or not CD was present, mania presented with a predominantly irritable mood, a chronic course, and was mixed with symptoms of major depression. Only two manic symptoms differed between those with versus without CD: “physical restlessness” and “poor judgment” were more common in the mania-with-CD group than in the mania-only group. Similarly, there were few differences in the frequency of CD symptoms between CD youth with and without comorbid mania. Nevertheless, it is important to assess for both diagnoses because delinquency and mania require different treatment strategies.

Although anxiety is frequently overlooked in studies of mania, pediatric studies of youth with panic disorder and youth with mania document a bidirectional overlap. Biederman, Faraone, Marrs, et al. (1997) found that subjects with panic disorder and agoraphobia had very high rates of mania (52% and 31%), which were greater than those observed among psychiatric controls (15%). Wozniak, Biederman, Kiely, et al. (1995) and Bowen, South, & Hawkes (1994) reported significantly more panic and other anxiety disorders in children with mania. These findings indicate that mania at any age is frequently comorbid with severe anxiety that requires additional clinical and scientific scrutiny.

There is an extensive and bidirectional overlap between mania and substance use disorders (SUD) in youth (Biederman, Wilens, et al., 1997; West et al., 1996; Wilens, Bierderman, Abrantes, Spencer, & Thomas, 1997b) as well as in adults. Juvenile-onset mania may be a risk factor for SUD. For example, a prospective study of children and adolescents with and without ADHD found that early-onset mania was a risk factor for SUD independently of ADHD (Biederman, Wilens, et al., 1997). Similarly, controlled studies in adults show that mania is often an antecedent and is strongly associated with SUD (Wilens et al., 1997b). Mania has also been shown to be overrepresented among youth with SUD (West et al., 1996; Wilens, Biederman, Abrantes, Spencer, & Thomas, 1997a).

Wilens et al. (1999) found that mania significantly increased the risk for SUD independently of conduct disorder. Furthermore, they reported that the risk for SUD was carried by those subjects with an adolescent-onset form of mania. While this may be consistent with the notion that, like adults, adolescents self-medicate manic symptoms with substances of abuse (Khantzian, 1997), it is also consistent with the hypothesis that child and adolescent onset mania are etiologically distinct forms of the disorder with different risk profiles and natural courses.