Many children and adolescents with manic/hypomanic symptoms do not meet the full DSM-IV criteria for bipolar I (BP-I) or bipolar II (BP-II) disorder and are instead classified as "bipolar not otherwise specified" (BP-NOS). A recent phenomenology study of pediatric bipolar patients found only small differences between those classified as BP-NOS and those who meet the full BP-I criteria. These few differences mostly focused on duration and severity of manic/hypomanic symptoms. Lead author David Axelson, MD, Assistant Professor of Psychiatry at the University of Pittsburgh School of Medicine–Western Psychiatric Institute and Clinic, and colleagues wrote, "To our knowledge, this is the first report on the systematic assessment and comparison of children and adolescents with BP-I, BP-II, and BP-NOS." Their findings were published in the October issue of Archives of General Psychiatry.

The researchers evaluated data collected at the initial intake assessment of the Course and Outcome of Bipolar Youth (COBY) study. Patients ages 7 through 17 were enrolled in the COBY study at Brown University (n = 144), the University of California at Los Angeles (n = 90), or the University of Pittsburgh Medical Center (n = 204). The majority of participants (65.5%) were recruited from outpatient programs, and the rest from inpatient units (14.8%), advertisements (14.2%), and other sources (5.5%). Investigators interviewed the children and their parents or primary caregivers using the Schedule for Affective Disorders and Schizophrenia for School-age Children (KSADS) and other measures of family history and functional impairment.

COBY investigators used DSM-IV criteria to diagnose BP-I and BP-II disorder. Patients were classified as BP-NOS if they did not meet DSM-IV criteria for BP-I or BP-II disorder but had experienced a period of elevated, expansive, or irritable mood, along with:

Two symptoms of mania (three, if mood was only irritable).

A change in functioning.

Mood symptoms lasting for at least four hours within a 24-hour period.

Symptoms occurring on at least four days (not necessarily consecutive) in their lifetime.

MANY SIMILARITIES, FEW DIFFERENCES

Many similarities between patients classified with BP-NOS and BP-I disorders emerged, including age at onset, duration of illness, comorbidities, types of manic symptoms, history of suicidal ideation, and lifetime rates of major depressive episodes. In fact, nearly all (96.6%) of the BP-NOS patients met the DSM-IV mania symptom criteria during their most severe mood episode if the symptom threshold was set to be at least mild severity, and 61.2% met the symptom criteria if the symptom threshold was set at a moderate severity. Most of the BP-NOS patients failed to meet the full criteria for BP-I disorder only because their symptoms did not meet the DSM-IV criterion of lasting for at least seven consecutive days for manic or mixed episodes or four days for hypomanic episodes. The COBY investigators commented, "Whether the duration criteria for manic or hypomanic episodes are appropriate for pediatric populations remains an empirical question for which the longitudinal component of the COBY study may provide some answers."

There were a few significant differences between the BP-I and BP-NOS groups. The BP-I patients had significantly higher rates of moderate to severe symptoms across all symptom categories and were more likely to exhibit hypersexuality and a decreased need for sleep. During the most severe episode, BP-I patients met, on average, one criterion more from the DSM-IV for manic or hypomanic episodes. The BP-NOS group had lower scores on the Mania Rating Scale of the KSADS during their most severe episode, less functional impairment during their most severe episode and in the month prior to intake, and lower rates of attempted suicides. BP-NOS patients were also less likely to have a history of psychosis, psychiatric hospitalization, or treatment with psychotropic medication.

A SIMILAR STORY FOR BIPOLAR II

The COBY study also looked at bipolar II (BP-II) disorder, but this group was small (n = 30), limiting the study’s ability to characterize and compare these patients. However, the authors noted that "overall there were few detectable differences between the subjects with BP-II [disorder] and the subjects with either BP-I or BP-NOS [disorder]." Demographic analysis showed that subjects in the BP-II group were older (in late puberty or postpubertal), had a later age at symptom onset, and were more likely to be female (60%). The BP-II group also had a higher rate of anxiety disorders than the other two groups and more suicide attempts among first-degree relatives compared with the BP-NOS group. In comparison with BP-I disorder, BP-II disorder was associated with lower rates of functional impairment and hospitalization.

A CAVEAT FOR DIAGNOSIS

Dr. Axelson told NeuroPsychiatry Reviews that this initial report from the COBY study is valuable because "it helps us understand that there are likely to be children and adolescents with bipolar disorder who do not meet the current DSM-IV criteria for a manic or hypomanic episode." However, he cautioned clinicians about how they apply this knowledge in clinical practice. Dr. Axelson noted, "The criteria for inclusion into the BP-NOS group was set intentionally low for research purposes so that we could enroll a broad spectrum of youth with manic symptomatology. They should not be used as clinical diagnostic criteria for youth with manic symptoms at this time." He added, "However, I think it is safe to say that clinicians should keep bipolar disorder in mind as a strong possibility in youth who have repeated, distinct, but relatively short episodes of clear manic symptomatology."

SOME ANSWERS, MORE QUESTIONS

The COBY authors concluded, "The fact that the subjects with BP-NOS [disorder] differed from those with BP-I [disorder] primarily on duration and severity of manic symptoms, but not on the fundamental phenomenology of manic symptoms, comorbid disorders, or family history, provides preliminary evidence that many of these subthreshold pediatric cases have a phenotype that is on the same continuum as that of youth with BP-I [disorder]." In discussing this issue further with NeuroPsychiatry Reviews, Dr. Axelson said, "We do not know enough yet to know whether these short periods of mania or hypomania [in BP-NOS patients] are an early manifestation of bipolar disorder, a milder variant, or whether in some cases they are not truly indicative of a bipolar disorder. Personally, I suspect that it is a combination of all three of these possibilities." There is some evidence, according to Dr. Axelson, that many adults with bipolar disorder have brief episodes of manic symptoms during the overall course of the illness, on the order of one to three days.

The prospective portion of the COBY study is ongoing. Dr. Axelson concluded, "The COBY study is a great resource to help answer many questions about the course and outcome of pediatric bipolar disorder, as we have the opportunity to follow these children and adolescents for five to nine years." Dr. Axelson expects COBY to shed light on whether most young persons with "subthreshold" bipolar symptoms go on to have clear bipolar disorder in late adolescence and early adulthood and to "provide some clues as to factors that are associated with conversion to a full threshold bipolar phenotype." Finally, he said, "We also plan to look at factors associated with a positive outcome versus a more difficult course of illness."

—Lauren Cerruto

Suggested Reading
Angst J, Gamma A, Benazzi F, et al. Toward a re-definition of subthreshold bipolarity: epidemiology and proposed criteria for bipolar-II, minor bipolar disorders and hypomania. J Affect Disord. 2003;73:133-146.
Axelson D, Birmaher B, Strober M, et al. Phenomenology of children and adolescents with bipolar spectrum disorders. Arch Gen Psychiatry. 2006;63:1139-1148.
Birmaher B, Axelson D, Strober M, et al. Clinical course of children and adolescents with bipolar spectrum disorders. Arch Gen Psychiatry. 2006;63:175-183.
Kowatch RA, Youngstrom EA, Danielyan A, Findling RL. Review and meta-analysis of the phenomenology and clinical characteristics of mania in children and adolescents. Bipolar Disord. 2005;7:483-496.

Return to table of contents