It May Be Time to Rethink Bipolar Classification in Youth

Various manifestations of childhood bipolar disorder, even those that don't meet full DSM-IV diagnostic criteria, are part of broader continuum of bipolar illness, according to a study of more than 400 children and adolescents.

The Course and Outcome of Bipolar Youth (COBY) study compared similarities and differences among subjects with bipolar disorder I (BP-I), bipolar disorder II (BP-II), and bipolar disorder not otherwise specified (BP-NOS).

David Axelson, M.D., an assistant professor of psychiatry at Western Psychiatric Institute and Clinic at the University of Pittsburgh Medical Center, and colleagues recruited 438 children and adolescents aged 7 to 17 years, 11 months (mean, 12.7 years) at medical centers at Brown University, the University of California at Los Angeles, and the University of Pittsburgh.

The subjects met DSM-IV criteria for BP-I or BP-II, or for the investigators' standards for BP-NOS. Those BP-NOS standards applied to subjects who lacked at least one required symptom, did not have a major depressive episode, or had a sufficient number and types of manic symptoms the duration of which fell short of DSM-IV criteria.

“BP-NOS in the DSM-IV is an extremely broad definition that is useful in clinical work because it predicts response in the future course of the illness,” said Barbara Gracious, M.D., director of the Laboratory for Mood Disorders in Children and Adolescents and director of child and adolescent psychiatry and assistant professor of psychiatry, obstetrics and gynecology, and pediatrics at the University of Rochester Medical Center.“ But for research, you need more specific criteria. Spelling those out in the study allows other psychiatrists to compare them with their own patients.”

The question facing the COBY researchers, Gracious told Psychiatric News, is “whether these are different but related disorders or are they manifestations of different points in the development of the disease?”

Study participants were evaluated with elements of the Schedule for Affective Disorders and Schizophrenia for School-Age Children (KSADS) in semistructured interviews and by interviewing the child's primary caregiver about the caregiver's psychiatric history as well as that of the subject's first- and second-degree relatives.

About 58 percent of the children met criteria for BP-I, 7 percent for BP-II, and 35 percent for BP-NOS. Subjects with BP-NOS had lower rates of lifetime history of psychosis, psychiatric hospitalization, psychotropic medication treatment, and suicide attempts than did those with BP-I. Subjects with BP-I had more of the seven DSM-IV criteria for manic or hypomanic episodes, at mild or higher severity, and had higher KSADS Manic Rating Scale scores than those with BP-NOS.

“During the most serious lifetime episode of manic symptoms, subjects with BP-I on average met one more DSM-IV manic symptom criterion compared with subjects with BP-NOS,” wrote Axelson and colleagues.“ The symptoms were more intense, and functional impairment was more severe in the BP-I group.”

However, youth with BP-NOS and those with BP-I shared similar age of onset, duration of illness, rates of comorbid diagnoses and prior major depressive episodes, family-history characteristics, and types of manic symptoms that were present during the most serious lifetime episode.

There were “few detectable differences” between participants with BP-II and those with BP-I and BP-NOS.

The primary reason that patients with BP-NOS did not achieve full diagnostic status was because they did not meet DSM-IV duration criteria. Those criteria call for seven consecutive days of manic symptoms in a manic or mixed episode or four consecutive days for a hypomanic episode.

“Most children and adolescents with BP-NOS have similar, albeit less severe, presentations as youth with BP-I disorder and have similar comorbidity and family histories,” they said. These similarities indicate that BP-NOS reflects a phenotype on the same continuum as BP-I among young people.

The COBY researchers are continuing to follow their subjects. Their preliminary observations indicate that many subjects with BP-NOS eventually meet DSM-IV standards for BP-I.

Some BP-NOS patients may progress to BP-I or BP-II, some may not change much, and some may have depression and conduct problems, said Gracious. Axelson's study was an important step forward, but only further genetic studies will tease out the differences, because bipolar disorders are not single-gene diseases, she said.

“This kind of research is extremely important for child psychiatry, but it's hard to get funding and hard to keep the patient population,” said Gracious. “Bipolar disorder in children wasn't even discussed until the 1990s. Studies that began then are only now starting to report results. You need a 15- to 20-year follow-up, but foundations and NIMH don't work that way. Researchers need to reapply for grants every two or three years.”

Still, she is hopeful that the mechanisms of bipolar disorder will become better known and that treatment, and possibly even prevention, will advance to permit these young patients to lead functional lives.

The COBY study was supported by the National Institute of Mental Health.

“Phenomenology of Children and Adolescents With Bipolar Spectrum Disorders” is posted at<http://archpsyc.ama-assn.org/cgi/content/full/63/10/1139>.▪