Manivel Rengasamy, M.D. Boris Birmaher, M.D. Pediatric bipolar II disorder (BD II) is characterized by episodes of hypomania alternating with episodes of major depression, consistent with DSM-5 BD II criteria for adults (American Psychiatric Association 2013). In this chapter, we provide relevant background information on pediatric bipolar I disorder (BD I), bipolar disorder not otherwise specified (BD NOS), and cyclothymic disorder, given the paucity of specific research focused on pediatric BD II and the similarities in demographics, comorbid disorders, course, and outcome among the different subtypes of bipolar disorder in pediatric populations. We draw on the adult BD II literature to highlight differences between pediatric and adult populations. We use the term youth to refer to children and adolescents. Significant psychosocial, psychiatric, and medical burden associated with BD II in adults has been discussed previously, including elevated suicide risk, comorbid substance use, poor psychosocial outcomes, and lower quality of life (see Part I, “Recognition,” in this volume). Pediatric bipolar spectrum disorders are associated with similar burdens and rank fourth among causes of disabilities among adolescents (Birmaher 2018; Gore et al. 2011). Because research on pediatric bipolar disorder remains in its infancy, studies on pediatric BD II are sparse. The historical characterization of BD II as a “less severe” form of the disease coupled with the fact that the 4-day minimum duration for hypomania required by DSM-5 is not met by many youth may also contribute to the limited number of studies that have been conducted on this topic. As we will describe, pediatric BD II appears to be associated with comparable disease burden as pediatric BD I, based on the adult literature and emerging pediatric literature. In youth, BD I is associated with elevated risk of legal charges, substance use disorders, interpersonal problems (e.g., peer and family relationships), dysfunction with mood regulation, psychiatric comorbidities, cardiometabolic risk, and neurocognitive deficits, compared with the general population (Birmaher 2018; Goldstein et al. 2017). The Course and Outcome of Bipolar Youth (COBY) study recruited 244 BD I youth, 28 BD II youth, and 141 youth with an operationalized criterion for BD NOS (Axelson et al. 2011). The youth were followed for 16 years, and diagnostic and biopsychosocial measures were obtained at approximately 2-year intervals. At baseline, youth with BD I and BD II showed similar rates of psychosocial impairment (e.g., domains of work, interpersonal interactions, satisfaction) (Goldstein et al. 2009) and onset of substance use (Goldstein et al. 2013). At 4-year follow-up, no differences were observed in prospectively examined suicide attempts (Goldstein et al. 2012) or nonsuicidal self-injurious behavior (Esposito-Smythers et al. 2010) between those with BD I and BD II, although individuals with BD II spent a greater amount of time in syndromal depressive episodes. Unlike depression, hypomania in BD II is often associated with improved psychosocial functioning, which is likely secondary to elevations in mood, productivity, and increased sociability (Birmaher 2018), although this has not been confirmed in studies of youth with bipolar spectrum disorders. Although presence of hypomania is required to make the diagnosis of BD II, youth with this diagnosis surprisingly spend less time in hypomania compared with their BD I counterparts (Birmaher et al. 2009a). Studies estimate the combined prevalence for pediatric BD I and BD II between 1.8% and 2.9% (Merikangas et al. 2010; Van Meter et al. 2011). A National Comorbidity Survey analysis of a smaller clinical reappraisal sample suggested a 2.8% lifetime prevalence of adolescent BD II, which is similar to the prevalence estimated by a large prospective community study (Kessler et al. 2009; Tijssen et al. 2010). Subsyndromal bipolar symptoms may exist in up to 6.7% of the population, 30% of whom may eventually convert to BD II (Axelson et al. 2011; Merikangas et al. 2011). Additionally, up to 40%–60% of adolescents with bipolar spectrum disorders may present with a depressive index episode, suggesting that current prevalence studies restricted to adolescents may underestimate the true prevalence of BD II (Birmaher et al. 2009a; Lewinsohn et al. 1995). BD II is defined by periods of hypomania lasting at least 4 days, alternating with major depressive episodes. Criteria for BD II have been discussed previously (see Chapter 2, “Diagnosing Bipolar II Disorder”). Growing evidence from the adult literature suggests that short-duration episodes of hypomania lasting <4 days are associated with psychosocial impairment and outcomes comparable to those of full-duration episodes (Angst et al. 2003). Consistent with this viewpoint, the ICD-10 only requires a duration of “at least several days” in order for criteria for an episode of hypomania to be met (World Health Organization 1992). Similar findings are noted in youth. Epidemiological studies suggest that greater than 50% of youth with bipolar spectrum diagnoses have presentations that meet DSM-IV criteria for BD NOS. Prospective studies of bipolar disorder such as COBY show similar rates of psychosocial impairment, suicide attempts, and family history of bipolar disorder in youth with bipolar disorder not otherwise specified (NOS) as compared with youth with BD I or BD II (Axelson et al. 2006; Van Meter et al. 2011), suggesting that short-duration hypomanias are associated with poor outcomes in youth. If the DSM-5 criteria for hypomania were revised to include shorter-duration episodes, many more youngsters would likely meet criteria for BD II. A recent meta-analysis of 20 studies with 2,226 youth with bipolar spectrum disorders found that irritable mood, increased energy, distractibility, pressured speech, and grandiosity were among the most common symptoms found during manic episodes, with a prevalence of around 70%–80% (Van Meter et al. 2016a). Hypersexuality, hallucinations, and delusions were the least prevalent, present in less than 50% of the sample, with hallucinations and delusions being more specific to pediatric BD I. Although irritability is common in pediatric BD spectrum disorders, pure “irritable” hypomania (i.e., no mood elevation) is uncommon, likely existing in less than 15% of BD II patients (Hunt et al. 2009). In our clinical experience, the phenomenology of (hypo)manic episodes is largely stable across age ranges, although adolescents may have more psychotic symptomatology than younger children. No epidemiological studies have directly assessed the prevalence of specific symptoms during episodes of pediatric bipolar depression. In contrast to adults, youth with unipolar depression appear to present with lower self-esteem, greater somatic complaints, greater agitation, less diurnal symptom variation, and fewer vegetative symptoms (Carlson and Kashani 1988). In contrast to unipolar major depressive disorder (MDD), preliminary evidence suggests that pediatric bipolar depression is characterized by greater levels of sadness, irritability, hopelessness, subsyndromal mania symptoms, social withdrawal, suicidality, and nonsuicidal self-injurious behavior (Diler et al. 2017). Several instruments are designed to aid in diagnosis of pediatric bipolar disorder. The Kiddie Schedule for Affective Disorders and Schizophrenia for School-Aged Children—Present and Lifetime Version (KSADS-PL) is a commonly used clinician-rated research instrument that requires 2–3 hours for completion (Goldstein et al. 2017). A section of the KSADS has also been used to ascertain manic symptoms (Axelson et al. 2003). Self-reports may be also useful to screen for the presence of manic/hypomanic symptoms, including the Child Mania Rating Scale and the General Behavior Inventory (short form), with greater accuracy found when using parent reports (Youngstrom et al. 2015). Various patient-guided instruments, including mood diaries, mood “thermometers,” online forums/websites, mobile applications, and mood timelines, may also be useful in assessing historical or “real-time” symptomatology (Birmaher 2018). Accurate diagnosis is critical for establishing appropriate treatment and potentially limiting negative outcomes associated with BD II. Clinical assessment in youth involves collaboration with parents and teachers in addition to patients, given variability in symptoms described by these reporters (Goldstein et al. 2017). Peer- or teacher-reported collateral may provide valuable information regarding these symptoms, which parents may not recognize. Assessment of BD II in youth demands careful, comprehensive, and prospective evaluation of hypomanic and depressive symptom history (Birmaher 2018). Evaluation of psychiatric comorbidities, medical comorbidities, family history, school reports, and relevant psychosocial factors aid in diagnosis as well. Assessment of antidepressants, other medications, and other substance use is needed to rule out other causes of hypomania or depression. Challenges associated with achieving an accurate diagnosis of hypomania include difficulty in differentiating normal from grandiose thoughts and normal silly/talkative behaviors from impulsivity. These difficulties are compounded by poor retrospective recall in youth, cognitive and emotional immaturity in youth, poor insight in youth, and difficulty in eliciting relevant symptoms in an age-appropriate manner. Thus, false negatives and positives in diagnosis are often present, emphasizing the critical need for close longitudinal follow-up. Symptoms should be assessed retrospectively and prospectively, with longitudinal follow-up for several months (or even years). Furthermore, symptoms should occur concurrently in clear discrete episodes across multiple settings (e.g., at school and home). Additionally, symptoms should not be better explained by comorbid disorders and circumstances. If symptoms occur in the context of a comorbid disorder, the comorbid symptoms (e.g., hyperactivity in a child with ADHD) get worse. Lastly, the described symptoms should be present above and beyond the normative cognitive and emotional developmental stage of the youth and above the youth’s baseline (e.g., presence of comorbid disorder that manifests with symptoms that overlap with BD). Although youth may present to outpatient clinics with symptoms of mania, over 75% of these youth likely will not have symptoms that meet criteria for bipolar disorder, perhaps less than 1% will have symptoms that meet criteria for BD II, and 12% will have symptoms that meet criteria for BD NOS (Findling et al. 2010). Youth often receive a diagnosis of another psychiatric disorder that has symptoms that overlap with those of bipolar disorder but are chronic rather than episodic in nature, including ADHD (hyperactivity, distractibility), oppositional defiant disorder (ODD) (risk-taking behavior, irritability), and disruptive mood dysregulation disorder (DMDD)/dysthymia (irritability). Such findings emphasize the critical need for longitudinal follow-up and assessment of clear episodes of co-occurring symptom elevation above patient’s baseline symptomatology. Importantly, many of these disorders are comorbid with BD II, as will be discussed later. Pediatric antidepressant-induced hypomania is often described in the first 2–3 weeks of treatment or an antidepressant dose increase, with mania spectrum conversion rates of 5.4% and hypomania conversion rates of <2%, based on two large studies (Amitai et al. 2015). In one retrospective study, 58% of 82 youth diagnosed with a bipolar spectrum disorder experienced treatment-emergent mania (Faedda et al. 2004). Stimulants, atomoxetine, oral corticosteroids, androgenic steroids, and drugs of abuse (e.g., cannabis, 3,4-methylenedioxymethamphetamine [MDMA], cocaine) may be associated with substance-induced hypomania. However, an episode of medication or substance-induced hypomania does not warrant a BD II diagnosis (unless hypomania persists beyond the physiological effect of treatment), although it may identify youth at elevated risk for BD II. Also, clinicians need to assess if risky behavior (e.g., illicit drug use) precedes or follows hypomanic symptoms, while continuing to monitor for bipolar spectrum symptoms. Similarly, medical comorbidities need to be ruled out on the basis of presenting symptoms, including hyperthyroidism or traumatic brain injury. Other medical comorbidities that may cause symptoms of hypomania or depression include hypothyroidism, B12 or folate deficiency, hypercalcemia, neoplasms, epilepsy, multiple sclerosis, pheochromocytoma, systemic lupus erythematosus, HIV, and Wilson’s disease. Electroconvulsive therapy–induced hypomania may theoretically occur. Larry is a 13-year-old male with prior diagnoses of ADHD and MDD. However, parents now report troublesome behaviors at school, including talking with peers during classroom lectures. Parents report he did not have these behaviors previously, and there have been no acute stressors. On interview with parents, they report 2- to 4-day periods, occurring about once every 4 months for the past 2 years, characterized by Larry being excessively talkative. Friends report being unable to understand his actual words because of his increased speech rate. During these times, he is often silly and immature with parents. For instance, he will repeat “A wood chuck would chuck wood” for 20 minutes and find this very amusing. They also note that he thinks he should be his class president, despite never having had mentioned this before. Per teacher reports, although he sometimes is off-task at his school normally, he is much more easily distracted by events occurring outside his classroom during these periods. Larry reports feeling “super awesome happy” during these episodes; there is no significant drop in academic performance or lost friendships. Given a prior history of depressive episodes and recurrent episodes of hypomania that last the required 4 days, Larry is given a diagnosis of BD II.
11
Bipolar II Disorder in Childhood and Adolescence
Importance of Early Recognition
Epidemiology
Diagnosis
Phenomenology
Hypomanic Episodes
Hypomanic Episodes: Special Considerations for Youth
Depressive Episodes
Depressive Episodes: Special Considerations for Youth
Clinical Assessment
Instruments
General Guidelines
Diagnosing Pediatric Bipolar II Disorder
Differential Diagnosis of Pediatric Bipolar II Disorder
Specific Diagnoses That May Be Confounded With BD II
Substance-Induced Hypomania and General Medical Causes of Hypomania
Case Vignette: Child With a Diagnosis of BD II and Features of Elation
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