Prepubertal and early adolescent bipolar I disorder: Review of diagnostic validation by Robins and Guze criteria

The phenomenology of pediatric bipolar disorder is a controversial topic in the field of child psychiatry. The first National Institute of Mental Health-funded study in the field, Phenomenology and Course of Pediatric Bipolar Disorders, selected a conservative phenotype for credibility in a contentious field. To address the problems of differentiation of mania from attention-deficit/hyperactivity disorder (ADHD) and of the ubiquitous manifestation of irritability across child psychiatry diagnoses, a prepubertal and early adolescent bipolar 1 disorder phenotype (PEA-BP) was defined by DSM-IV bipolar 1 disorder (manic or mixed phase) with elation and/or grandiosity as one criterion. This criterion avoided diagnosing mania by symptoms that overlapped with those of ADHD (e.g., hyperactivity, distractibility) and ensured that subjects had at least 1 of the cardinal symptoms of mania (i.e., elation or grandiosity). This definition was analogous to the requirement that DSM-IV major depressive disorder include at least I of the cardinal symptoms of depression (i.e., sad mood or anhedonia). Subjects were 93 children with a mean +/- SD age of 10.9 +/- 2.6 years. Validation of the phenotype was shown according to Robins and Guze criteria: unique symptoms that did not overlap with those of ADHD, stability of the diagnosis (did not become ADHD or other disorders on follow-up) as shown by a 4-year prospective longitudinal study, significantly higher familial aggregation of bipolar disorder in relatives of PEA-BP versus ADHD and healthy control probands, and family-based linkage disequilibrium of the brain-derived neurotrophic factor Va166 allele in PEA-BP probands. Furthermore, PEA-BP resembled the most severe adult bipolar disorder, manifested by a chronic, ultradian-cycling, mixed manic, psychotic course. A conservatively defined child mania phenotype met the Robins and Guze criteria for establishing diagnostic validity in psychiatric illness. Continuities between PEA-BP and adult bipolar disorder and relationships of PEA-BP to other descriptions of child mania are discussed.