INTRODUCTION — Bipolar disorder in children and adolescents is characterized by recurrent episodes of elevated mood (mania or hypomania), which exceed what is expected for the child's developmental stage and are not better explained by other psychiatric and general medical conditions [1-4]. In addition, youth with bipolar disorder usually have recurrent episodes of major depression; however, depressive episodes are not necessary for making the diagnosis. Pediatric bipolar disorder severely affects normal development and psychosocial functioning and increases the risk for behavioral, academic, social, and legal problems, as well as psychosis, substance abuse, and suicide [1,2,5].

Pediatric bipolar disorder is usually characterized by psychiatric comorbid conditions, and many bipolar patients have multiple comorbid illnesses [6,7]. The presence of comorbidities in youth with bipolar disorder may hinder clinicians from recognizing bipolar disorder. Clinicians should identify and treat comorbidities because they may adversely affect response to treatment of bipolar disorder and the course of illness [6,8,9].

This topic describes the comorbid psychiatric and general medical illnesses that commonly occur in pediatric bipolar disorder. The epidemiology, pathogenesis, clinical features, assessment, diagnosis, and treatment of bipolar disorder in children and adolescents are discussed separately.

●(See "Pediatric bipolar disorder: Epidemiology and pathogenesis".)

●(See "Pediatric bipolar disorder: Clinical manifestations and course of illness".)

●(See "Pediatric bipolar disorder: Assessment and diagnosis".)

●(See "Pediatric bipolar disorder: Overview of choosing treatment".)

●(See "Pediatric bipolar major depression: Choosing treatment".)

●(See "Pediatric bipolar disorder and pharmacotherapy: General principles".)

●(See "Pediatric mania and second-generation antipsychotics: Efficacy, administration, and side effects".)

●(See "Pediatric bipolar disorder: Efficacy and core elements of adjunctive psychotherapy".)

DEFINITION OF BIPOLAR DISORDER — Bipolar disorder is characterized by episodes of mania (table 1) and/or hypomania (table 2); in addition, episodes of major depression (table 3) usually occur [4]. According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, published in 2013, the subtypes of bipolar disorder include bipolar I disorder, bipolar II disorder, cyclothymic disorder, and other specified bipolar disorder. The clinical features and diagnosis of these subtypes are described separately. (See "Pediatric bipolar disorder: Clinical manifestations and course of illness" and "Pediatric bipolar disorder: Assessment and diagnosis", section on 'Bipolar disorders'.)

PSYCHIATRIC COMORBIDITY — Pediatric bipolar disorder is usually associated with other psychiatric conditions (eg, anxiety disorders, substance abuse disorders, and attention deficit hyperactive disorder), and many bipolar patients have multiple comorbid illnesses [6,7]. Clinicians should identify and treat comorbidities because they may adversely affect response to treatment of bipolar disorder and the course of illness [6,8,9].

Comorbid psychiatric disorders in adults with bipolar disorder are discussed separately. (See "Bipolar disorder in adults: Clinical features", section on 'Psychiatric disorders'.)

Anxiety disorders — In youth with bipolar disorder, the prevalence of comorbid anxiety disorders ranges from approximately 40 to 66 percent, as indicated by nationally representative community surveys, as well as studies in clinical settings and studies of administrative claims databases [7,9-11]. The temporal sequence of bipolar disorder and co-occurring anxiety disorders is such that anxiety disorders typically arise prior to onset of the first manic episode [12-15].

A prospective observational study found that the prevalence of specific anxiety disorders in youth with bipolar disorder (n = 413) was as follows [16]:

●Separation anxiety disorder – 46 percent of patients

●Generalized anxiety disorder – 43 percent

●Social anxiety disorder – 28 percent

●Panic disorder – 20 percent

Some youth had more than one comorbid anxiety disorder.

Pediatric bipolar disorder mood episodes are more likely to recur in patients with comorbid anxiety disorders than patients without comorbidity, and mood symptoms persist longer in patients with comorbid anxiety disorders [16]. In addition, co-occurring anxiety disorders tend to persist; a five-year prospective study of children and adolescents with bipolar disorder found that among those with anxiety disorders during follow-up (n = 137), the average duration of the anxiety disorder was approximately one year [17].

The clinical features and diagnosis of pediatric anxiety disorders are discussed separately. (See "Anxiety disorders in children and adolescents: Epidemiology, pathogenesis, clinical manifestations, and course" and "Anxiety disorders in children and adolescents: Assessment and diagnosis".)

Attention deficit hyperactivity disorder — Among youth with bipolar disorder who present to clinical settings, approximately 50 percent have comorbid attention deficit hyperactivity disorder (ADHD) [9,18]. This estimate is based upon a meta-analysis of 20 observational studies that included youth with bipolar I disorder and other specified bipolar disorder (total n >2000, average age 11 years) [18], as well as a pooled analyses of 14 observational studies (number of patients not reported) [9]. Onset of ADHD typically predates onset of the first manic episode [12,13,19].

Among youth who are treated for bipolar disorder, comorbid ADHD is associated with poorer outcomes. As an example, a meta-analysis of five observational studies of children and adolescents with bipolar disorder (n = 273) found that treatment response was worse in youth with comorbid ADHD than youth without ADHD (relative risk 0.82, 95% CI 0.69-0.97) [20].

The clinical features and diagnosis of ADHD are discussed separately. (See "Attention deficit hyperactivity disorder in children and adolescents: Clinical features and diagnosis".)

Oppositional defiant disorder — In youth with bipolar disorder, the prevalence of comorbid oppositional defiant disorder is approximately 40 percent [18]. The clinical features of oppositional defiant disorder are described the table (table 4).

Conduct disorder — In children and adolescents with bipolar disorder, the prevalence of comorbid conduct disorder is roughly 30 percent [18]. The clinical features of conduct disorder are described in the table (table 4).

Substance use disorder — Studies in clinical settings and in the general population indicate that among adolescent (age ≥13 years) patients with bipolar disorder, the prevalence of comorbid substance use disorder is roughly 20 to 30 percent; in children (age <13 years) with bipolar disorder, the prevalence is 0 percent [9,10,21,22].

Bipolar disorder tends to emerge in youth prior to the onset of substance use disorders [22,23]. Beginning in adolescence, the rate of comorbid substance abuse progressively increases with age [24], such that substance use disorders occur more often in youth with bipolar disorder than in healthy controls and youth with other psychiatric disorders [22]. Comorbid substance use disorders commonly include cannabis and alcohol [21,23,25,26]. Suicide attempts, legal problems, and functional impairment are more common in youth with bipolar disorder plus substance use disorders, compared with youth with bipolar disorder alone [26,27]. In addition, time to recovery from depressive episodes worsens as the severity of substance use worsens [28]. A prospective observational study found that among adolescents with bipolar disorder who do not have a comorbid substance use disorder when they first present (n = 167), experimentation with alcohol at the start of the study was the single strongest predictor of later substance abuse, although experimentation with cannabis also predicted later substance abuse. Other risk factors for developing a substance use disorder include greater severity of hypomanic/manic symptoms; poor family functioning; lifetime history of alcohol use (experimentation), panic disorder, or oppositional defiant disorder; and family history of substance use disorder [21]. Among teens with three or more risk factors, 54.7 percent went on to develop substance abuse, compared with 14.1 percent of teens with zero to two risk factors. This study suggest that there may be a window of two to three years during which clinicians can attempt to prevent substance abuse in these youth by targeting these risk factors.

Other — Other less common comorbid disorders observed in pediatric bipolar disorder include autism spectrum disorder, obsessive compulsive disorder, and posttraumatic stress disorder [9,16,29-32]. In addition, some adolescents with bipolar disorder have comorbid symptoms of borderline personality disorder (eg, identity confusion, interpersonal problems, impulsivity, and emotional dysregulation) [33].

GENERAL MEDICAL COMORBIDITY — Youth with bipolar disorder appear to be at increased risk of comorbid general medical disorders, including cardiovascular disease, neurologic disorders, and respiratory disorders. One study of medical claims data found that in youth with bipolar disorder (n >800), treatment for comorbid chronic medical conditions occurred in approximately 75 percent [34]. Across multiple studies of claims data, roughly 25 to 33 percent of bipolar patients had multiple medical comorbidities [19,34]. In many instances, co-occurring general medical disorders predate onset of bipolar disorder [19].

The increased risk of comorbid general medial illnesses in youth with bipolar disorder may be due to biologic vulnerability and poorer access to medical care [34]. In addition, patients treated for bipolar disorder may receive greater monitoring of overall health, leading to detection of general medical problems that might not otherwise be observed.

Comorbid general medical disorders in adults with bipolar disorder is discussed separately. (See "Bipolar disorder in adults: Clinical features", section on 'General medical illnesses'.)

Cardiovascular — Bipolar disorder in adolescence may be associated with premature atherosclerosis and cardiovascular disease [35]. The mechanism appears to involve multiple systemic processes, including inflammation, oxidative stress, and autonomic dysfunction. Several traditional cardiovascular risk factors (eg, diabetes mellitus, sedentary lifestyle, and tobacco smoking) are more prevalent among adolescents with bipolar disorder compared with the general pediatric population. Although psychotropic medication may contribute to the elevated risk of cardiovascular disease, it appears that the association between bipolar disorder and cardiovascular disease is independent of medication effects. Based upon available data, the American Heart Association proposed in a 2015 statement that bipolar disorder be positioned alongside other pediatric diseases (chronic inflammatory disease, infection with the human immunodeficiency virus, Kawasaki disease, and nephrotic syndrome) that are considered moderate risk conditions for early cardiovascular disease [35]. Additional information about risk factors for pediatric atherosclerosis is discussed separately, as is the management of youth at risk for atherosclerosis (algorithm 1). (See "Overview of risk factors for development of atherosclerosis and early cardiovascular disease in childhood" and "Overview of the management of the child or adolescent at risk for atherosclerosis".)

Studies of medical claims data have found that the prevalence of cardiovascular disease was 40 to 100 percent greater in children and adolescents with bipolar disorder, compared with control groups:

●In one study of an administrative claims database that identified youth with bipolar disorder (n >800) and youth with other psychiatric disorders (n >21,000), youth with bipolar disorder were twice as likely to have comorbid cardiovascular disease (odds ratio 2.0, 95% CI 1.6-2.4) [34].

●A second study of medical claims identified youth with bipolar disorder (n >1800) and youth with no psychiatric disorders (n = 4500), and found that youth with bipolar disorder were 40 percent more likely to have comorbid cardiovascular disease (odds ratio 1.4, 95% CI 1.1-1.8), such as arrhythmias and congestive heart failure [19].

Excess weight and obesity — Many children and adolescents with bipolar disorder are overweight or obese, at rates comparable to those in the general population. Studies in both community and clinical samples of youth with bipolar disorder suggest that excess weight (body mass index 85th to <95th percentile) is observed in 20 to 25 percent, and that obesity (body mass index ≥95th percentile) occurs in approximately 17 percent:

●A nationally representative survey of adolescents in the United States (n >10,000) found that among those with bipolar disorder (n = 295), 21 percent were overweight and 17 percent were obese, which was comparable to the weight status of controls [36].

●An observational study of patients with pediatric bipolar disorder (n = 348) found that at study intake, 25 percent were overweight and 17 percent obese [37]. These rates were roughly comparable to published rates in the United States population.

●A retrospective study found that at study intake, obesity was present in 18 percent of adolescents with bipolar disorder [38].

A history of physical abuse in patients with pediatric bipolar disorder appears to be associated with excess weight or obesity [36,37].

Juvenile bipolar disorder is often treated with second generation antipsychotics, which can cause weight gain and may also be associated with diabetes. (See "Pediatric mania and second-generation antipsychotics: Efficacy, administration, and side effects", section on 'Weight gain'.)

Other disorders — Studies of medical claims data have found that the prevalence of neurologic, respiratory, and other chronic general medical disorders was greater in children and adolescents with bipolar disorder, compared with control groups. In addition, roughly 25 to 33 percent of patients had multiple medical comorbidities:

●In one study of an administrative claims database that identified youth with bipolar disorder (n >800) and youth with other psychiatric disorders (n >21,000), youth with bipolar disorder were more likely to have comorbid neurologic disorders, respiratory disorders, gastrointestinal and hepatic disorders, and female reproductive disorders [34]. Many youth with bipolar disorder had more than one comorbidity, and multiple medical comorbidities were observed in more youth with bipolar disorder than controls (36 versus 8 percent).  

●A second study of medical claims identified youth with bipolar disorder (n >1800) and youth with no psychiatric disorders (n = 4500), and found that the prevalence of epilepsy, migraine headaches, neurodevelopmental disorders (eg, intellectual disability), asthma, and endocrine disorders was greater in youth with bipolar disorder than controls [19]. Among children and adolescents with bipolar disorder, 28 percent had two or more comorbid illnesses.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Bipolar disorder".)

SUMMARY

●Bipolar disorder is characterized by episodes of mania (table 1) or hypomania (table 2), and often periods of major depression (table 3). The subtypes of bipolar disorder include bipolar I disorder, bipolar II disorder, cyclothymic disorder, and other specified bipolar disorder. (See "Pediatric bipolar disorder: Clinical manifestations and course of illness" and "Pediatric bipolar disorder: Assessment and diagnosis", section on 'Bipolar disorders'.)

●Pediatric bipolar disorder is usually characterized by psychiatric comorbid conditions, and many bipolar patients have multiple comorbid illnesses. Comorbidities may adversely affect response to treatment of bipolar disorder and the course of illness. The prevalence of common comorbidities is approximately as follows:

•Anxiety disorders – 40 to 66 percent of youth with bipolar disorder

•Attention deficit hyperactivity disorder – 50 percent

•Disruptive behavior disorders – 40 percent

•Conduct disorder – 30 percent

•Substance use disorder – 20 to 30 percent

(See 'Psychiatric comorbidity' above.)

●Youth with bipolar disorder appear to be at increased risk of comorbid general medical disorders, particularly cardiometabolic conditions. Comorbid chronic medical conditions may occur in approximately 75 percent bipolar patients, and roughly 25 to 33 percent of bipolar patients have multiple medical comorbidities (See 'General medical comorbidity' above.)