Researchers Refine Criteria for Childhood Bipolar Disorder

The intramural debate on the differential diagnosis of bipolar disorder in children and adolescents is unlikely to find a quick resolution. Part of the reason is the complexity of symptom presentation in these children and the frequent overlap with other disorders, said Boris Birmaher, M.D., who chaired a session on the topic at the annual meting of the American Academy of Child and Adolescent Psychiatry in Chicago last October.

“In bipolar, symptoms fluctuate and appear in addition to a child's other psychiatric disorders,” said Birmaher, a professor of psychiatry, director of the child and adolescent anxiety program, and co-director of the child and adolescent bipolar services at the University of Pittsburgh's Western Psychiatric Institute and Clinic.

Hundreds of potential comorbidities make everything murkier, he said. Not just psychopathology, but also family and neighborhood environments may affect the child. Even terminology that might apply to adults becomes more difficult with children. “Grandiosity” among adults may seem clear, but how does it manifest in children, who normally have an imagination not always constrained by what adults call reality? What limitations are imposed by a child's abilities to express emotions and cognitions?

Birmaher noted the discussion among practitioners on the relative significance of irritability and elation or grandiosity as hallmarks of the disorder—a topic taken up by Jeffrey Hunt, M.D., of Bradley Hospital in East Providence, R.I., and an associate professor of psychiatry and human behavior and the Warren Alpert Medical School of Brown University.

As part of the ongoing Course and Outcome of Bipolar Youth (COBY) study, Hunt studied the presence of irritation versus elation as symptoms of pediatric bipolar disorder. Prior information on the topic was contradictory, with different researchers concluding that one was more common than the other, he said. COBY is a longitudinal, multisite study of children ages 7 to 17 years, 11 months. Data were collected on 446 patients from 2000 to 2006. Continuing follow-up in the study is funded through July 2011.

Hunt studied data from the 413 patients for whom follow-up data were available. Of those, 36 individuals exhibited irritability only, 54 had only elation as a symptom, and 271 had both. Individuals in the irritable group were two years younger on average than those in the other groups but had no differences in comorbidities. Members of the “both” group were more impaired.

Hunt found, at 12-month follow-up, that the number of irritable-only patients remained stable but the elation-only cohort had developed some irritability. There were no differences in bipolar category B symptoms and no specific comorbidities associated with these differences. About 20 percent of the children in all three groups relapsed into mania. However, only 14 percent of those in the irritable group relapsed into depression compared with 47 percent of those in the elation cohort.

“This suggests that at 12 months of follow-up, irritability may be a stable phenotype,” he said. The episodic nature of irritability differentiated its presence in bipolar disorder from ordinary childhood behavior. “Future research should include subjects with episodic irritability, follow patients for longer periods of time, and incorporate neuropsychological and neuroimaging testing.”

“The key to diagnosis is the episodic nature of the illness,” said Ellen Liebenluft, M.D., of the National Institute of Mental Health.“ You don't diagnose mania with DSM-IV; you diagnose a manic episode.”

In effect, each child serves as his or her own control. The clinician must ask if the child is more manic or elated than at some previous time. Bipolar B criteria must have occurred at the same time as the episode, but some symptoms have to be worse than at other times, she said.

However, some cases exhibit a chronic presentation, with no discernable episodes, sometimes with overlapping ADHD symptoms, as well. She refers to this pattern of behavior as severe mood dysregulation (SMD).

“SMD does not have a good home in DSM-IV,” she said.“ The data suggest that SMD is not a developmental phenotype of bipolar disorder. It predicts anxiety and depression in adults, but not necessarily bipolar disorder.”

Bipolar children and SMD children share some attributes, she said. Both have difficulty identifying facial emotions, while children with major depression and anxiety respond to faces more like healthy controls. Functional MRI testing reveals that ADHD children have increased left amygdala activation while SMD children have lower activation. Bipolar children exhibit no change in the test “but that may be due to a Type II [false negative] error,” she said.

The reduced activation of the amygdala may mean that these children are depressed or are at increased risk for depression, she said. “It also raises the issue of where do emotional disorders end and behavioral disorders begin? We don't know, but we have to look more closely at the boundary between the two.”

Tina Goldstein, Ph.D., of the Western Psychiatric Institute and Clinic, examined data from the 413 patients in the COBY study. Of the group, 53 attempted suicide, mostly in the first year of follow-up. The most common means of harm was cutting, followed by overdoses of household chemicals. About 57 percent of those who attempted suicide said they were ambivalent about dying, but 41 percent said they had a moderate to severe intent to kill themselves. She said that the suicide attempts of 37 percent of the patients were preceded by a significant life event, like family conflict, death in the family, or a romantic breakup.

Youth with bipolar disorder are at higher risk for suicide, Goldstein reiterated. Clinicians should assess for risk factors, like a history of suicide attempts, comorbid anxiety, mixed bipolar episodes, or a family history of suicidality.

“Treat suicidality itself separately from Axis I diagnoses,” said Goldstein. She is now conducting an open trial of dialectica-behavioral therapy developed originally for borderline personality disorder to see if it will reduce suicidality in the COBY population. ▪