Research on prepubertal bipolar disorder

On April 27, 2000, the National Institute of Mental Health (NIMH) Developmental Psychopathology and Prevention Research Branch, in collaboration with the Child and Adolescent Treatment and Preventive Intervention Research Branch, convened a small roundtable meeting to discuss possible approaches to outstanding issues for research on prepubertal bipolar disorder.

The major questions were:

• How early can bipolar disorder be diagnosed?
• What is the predictive value of the early manifestations of bipolar illness in children (before puberty) in adolescents?
• What is the risk/benefit ratio of treating children and adolescents with "prodromal" symptoms? Which treatments should be considered? For how long?
• What is the potential impact of early treatment on course of illness?

Participants

Joseph Biederman, M.D., Boris Birmaher, M.D., Gabrielle Carlson, M.D., Kiki Chang, M.D., Barbara Geller, M.D., Kenneth Kendler, M.D., Robert Kowatch, M.D., David Kupfer, M.D., and Elizabeth Weller, M.D. NIMH participants were Wayne Fenton, M.D., Kimberly Hoagwood, Ph.D., Steven Hyman, M.D., Doreen Koretz, Ph.D., Ellen Leibenluft, M.D., Richard Nakamura, Ph.D., Editha Nottelmann, Ph.D., Ellen Stover, Ph.D., Benedetto Vitiello, M.D., and Gemma Weiblinger.

Meeting Summary

Open-ended discussion centered on two inter-related issues: (a) clinical assessment for treatment disposition and (b) definition of phenotype for resolving questions of nosology (the treatment questions remain to be addressed). Relevant to both is ascertainment (whether clinic-based, school-based, or community- or population-based) with specification of inclusion and exclusion criteria.

There was general agreement that a diagnosis of bipolar disorder, using DSM criteria, is possible in prepubertal children. Children seen in clinics fall into two categories: (1) those who clearly have a bipolar disorder (because they meet DSM-IV criteria for Bipolar I or II) and (2) those who may be bipolar, but do not fit the adult phenotype defined in DSM-IV. That is, some children meet full criteria for Bipolar-I or Bipolar-II, as currently defined; and children who do not meet full criteria, but suffer from mood disturbances and symptoms of bipolar disorder and are severely impaired, currently receive a diagnosis of "Bipolar-NOS." One estimate was that approximately 40% of children presenting at clinics with bipolar disorder are likely to be in the first category and approximately 60% in the second category.

Discussion resulted in agreement on two basic definitions:

• a narrow phenotype that adheres strictly to Bipolar-I and Bipolar-II criteria; and
• a broader phenotype that encompasses more heterogeneity, basically Bipolar-NOS, and includes children who do not quite meet criteria, but still are severely impaired by symptoms of mood instability.

Narrow phenotype: Consensus on the narrow phenotype was that it can be diagnosed with available psychiatric assessment instruments; e.g., the semi-structured K-SADS. For clear communication, however, it was suggested that it should be important to establish thresholds for boundaries between bipolar disorder subtypes (Bipolar-I, Bipolar-II, cyclothymia), as homogeneity is essential for biological and genetic research.

Broader phenotype: Currently, severely impaired children with impairing mood disturbance, but not meeting full DSM-IV criteria for Bipolar I or II, are not included in research studies because of the perceived uncertainty of their diagnosis. Still, there is a need to study these children because of their significant impairment. They should be included in appropriate research protocols. In general, it was agreed that "Bipolar-NOS" could be used as a "working diagnosis" for advancing research on this broader phenotype, as long as the children are well described (with particular attention to symptoms of ADHD). As available diagnostic instruments may not generate a reliable and replicable diagnosis of Bipolar-NOS, it was recommended that careful assessment include all of the behaviors that are impairing, giving consideration when relevant to the frequency with which they occur as well as to severity; e.g.,

Aggressiveness, agitation, explosiveness

Irritability

Mood lability (fluctuation independent of input)

Thought disorder (paranoia, misinterpretation of social cues)

Communication disorder (pragmatic language disorder than can look like flight of ideas;

receptive and expressive language disorder than can interfere with the accurate performance and interpretation of structured interviews)

Cognitive ability/cognitive impairment (significantly low IQ, reading disabilities)