Pediatric Bipolar Disorder

Introduction

The recognition, diagnosis, and treatment of pediatric bipolar disorder have undergone a number of changes over the last 30 years in the field of child and adolescent psychiatry. In a review of the history of pediatric bipolar disorder, Glovinsky noted descriptions of mania and melancholy that go all the way back to ancient Greece. However, it was the French in the 1670s who described melancholicus mania, which evolved into the folie circulaire in 1854 under the team at the La Salpetriere hospital. Kraepelin in Germany described manic depressive illness. The US definition of bipolar disorder did not become prominent until the 1950s, and the concept of bipolar disorder in children did not become widely recognized until decades later when child psychiatry separated from psychoanalysis and embraced the field of biologic psychiatry. While people did have clinical descriptions of bipolar disorder in isolated children in the literature, the first case series was a 1920s collection of 10 children out of 5000 consecutive admissions. After Kanner’s 1935 textbook, little was said in American psychiatry until much later in the century due to the psychoanalytic influence on the field. Even today with excellent diagnostic criteria and treatment protocols for both medication and therapy, controversy surrounds the diagnosis of pediatric bipolar disorder. The field has ranged over the last 30 years from underdiagnosis in the 1990s to increasing awareness and then claims of overdiagnosis. Several authors have examined this controversy and claim that children with chronic irritability are misdiagnosed as bipolar when they actually have disruptive mood disorder with dysthymia (see Chapter 4 ). One review by James and colleagues compared the rates of diagnosis at discharge in England and the United States from 2000 to 2010 in pediatric patients aged 1–19 years. The rates of pediatric bipolar disorder at discharge were 12.5-fold higher in the United States, whereas adult bipolar rates were 7.2-fold higher and other pediatric diagnoses at discharge were 3.9-fold higher in England. The authors postulated the difference was due to disparate diagnostic practices between the two countries.

Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition Definition

In Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition ( DSM-5 ), to meet criteria for bipolar disorder one must have met criteria for at least one manic episode. This includes an elevated, expansive, or irritable mood for most of the day nearly every day for at least a week or for any duration if hospitalized. While in the altered mood state, one must have at least three or four (if mood is primarily irritable) of the following symptoms: inflated self-esteem or grandiosity, decreased need for sleep (not insomnia), more talkative or pressured speech, flight of ideas or racing thoughts, distractibility, increase in goal-directed activity or psychomotor agitation, and excessive involvement in activities that have a high potential for painful consequences. The mood must cause impairment in social or occupational (school for kids) functioning or require hospitalization or have psychotic features. The episode cannot be due to the effects of a substance or another medical condition. One departure from DSM-IV-TR is that if mania merges with antidepressant treatment (medication or electroconvulsive therapy (ECT)) and persists at full syndromal level after the effects of treatment are gone, the individual is in a real manic episode and meets criteria for bipolar I disorder (BPI). Hypomania has the same criteria but requires only 4 days of symptoms without hospitalization, the mood and functioning changes are observable by others, and the functioning is not severely disturbed. If a person with suspected hypomania has psychotic features, they are by definition manic and not hypomanic.

Several symptoms of bipolar disorder can overlap with more common childhood disorders, such as attention deficit hyperactivity disorder (ADHD). To help clinicians distinguish pediatric bipolar disorder from the much more common childhood disorder, Dr Barbara Geller and colleagues conducted a large study comparing the frequency of different DSM-IV symptoms in both disorders. They determined that five cardinal symptoms were much more common in youth with bipolar disorder than in those with ADHD or normal controls. These cardinal symptoms were elation, grandiosity, flight of ideas/racing thoughts, decreased need for sleep, and hypersexuality. They noted that irritability, hyperactivity, accelerated speech, and distractibility were common in both groups.

Differential Diagnosis

The differential diagnosis of bipolar disorder in children and adolescents is similar to that seen in adults. It is described in both DSM-5 and Kaplan and Sadock’s Synopsis of Psychiatry . The differential includes multiple medical and psychiatric illnesses, including the effects of prescription medications (steroids, antiepileptic drugs, antidepressants, stimulants); illicit drugs (ketamine, phencyclidine, amphetamines, lysergic acid diethylamide); medical illnesses (lupus, brain tumor, hyperthyroidism); and psychiatric differential, including psychotic disorders, oppositional defiant disorder, conduct disorder, anxiety disorders, ADHD, mood disorders due to a medical condition, and substance-induced mood disorder.

Epidemiology and Genetics

The prevalence of BPI in the general population is approximately 1% and when one expands to the bipolar spectrum (bipolar II [BPII] and cyclothymia) the rate increases to 4%–6% of the population. The majority of adult patients remember a pediatric onset, including prepubertal episodes. In examining adults with bipolar disorder using retrospective interviews, approximately 30% had a very early onset and 40% had an adolescent onset. A metaanalysis of pediatric bipolar disorder yielded a rate of 1.8% of the US population.

Bipolar disorder runs in families and having a parent or sibling with the disease increases the risk. The risks of bipolar disorder range from 15%–30% with one affected parent to 50%–75% when both parents have the disorder. For siblings and dizygotic twins the rate is similar, from 15% to 25%, whereas the concordance rates in monozygotic twins range from 60% to 80%.

One large genetic investigation examined participants from the Treatment of Early Age Mania (TEAM) study and adult samples of those with early-onset bipolar disorder versus normal controls in a genetic risk score analysis. They examined 8 candidate SNPs in the 69 TEAM subjects, 732 adult patients with early-onset BPI, and 776 controls and found that the CACNA1C (calcium channel, voltage-dependent, L type, α 1C subunit) haplotype was associated with early-onset bipolar disorder. The same group examined brain-derived neurotrophic factor and found an association with the rs6265 minor allele in the TEAM and early-onset bipolar groups.

Common Comorbidity

A variety of illnesses can cooccur with bipolar disorder in adults and children. Some of the more common comorbid psychiatric disorders include ADHD, anxiety disorders, substance use disorders (SUD), and alcohol dependence. A recent review of 167 studies between 1990 and 2014 noted that pediatric bipolar disorder had common comorbidities, including anxiety disorders (54%), followed by ADHD (48%), disruptive behavior disorders (oppositional defiant disorder or conduct disorder) (31%), and SUD (31%). The team also noted that having comorbid anxiety disorder or ADHD had a negative impact on symptoms and clinical course, neurocognitive profile, and overall functioning. The youth with both bipolar disorder and ADHD did respond in controlled trials to both stimulants and atomoxetine over placebo.