National Institute of Mental Health (NIMH)
Workshop on Prepubertal Bipolar Disorder
March 10 - 11, 1997 • Bethesda, MD
Agenda
| Monday, March 10 |
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| 8:30 a.m. | Welcome Steven Hyman, M.D., Director, NIMH David Shore, M.D., Acting Director, DCTR, NIMH Peter Jensen, M.D.,Chief, CADRB, DCTR, NIMH |
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| 8:45 a.m. | Orientation to Workshop Editha Nottelmann, Ph.D., CADRB, DCTR, NIMH |
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| Chair, Day 1 Editha Nottelmann, Ph.D. |
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| Overviews |
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| 9:00 a.m. | Features of prepubertal, adolescent, adult bipolar disorder Gabrielle Carlson, M.D., SUNY at Stony Brook |
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| 9:25 a.m. | Discussion |
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| 9:35 a.m. | A model for the study of child and adolescent psychopathology:
Its utility with bipolar disorder, ADHD, ODD, CD, and emotional lability Dennis Cantwell, M.D., UCLA |
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| 10:20 a.m. | Discussion |
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| 10:45 a.m. | Development of emotion regulation in early childhood: Typical
and atypical development Pamela Colt, Ph.D., Pennsylvania State University |
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| 11:10 a.m. | Discussion |
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| 11:20 a.m. |
What is known and not known about childhood temper tantrums |
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| 11:45 a.m. | Discussion |
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| 1:00 p.m. | Can we identify temperamental and other early indicators of
bipolarity? Implications for prepubertal bipolar disorder Hagop Akiskal, M.D., UCSD |
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| 1:25 p.m. | Discussion |
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| 1:35 p.m. | Genetic anticipation in bipolar disorder Melvin McInnis, M.D., Johns Hopkins University |
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| 2:00 p.m. | Discussion |
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| Case Presentations |
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| 2:15 p.m. | Elizabeth Weller, M.D., University of Pennsylvania |
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| 2:45 p.m. | Discussion |
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| 2:55 p.m. | Adelita Segovia, M.D., Washington University |
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| 2:25 p.m. | Discussion |
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| 3:50 p.m. | Gabrielle Carlson, M.D., SUNY at Stony Brook |
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| 4:20 p.m. | Discussion |
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| 4:30 p.m. | General Discussion of Overview and Case Presentations Special Considerations in the Assessment of Prepubertal Bipolar Disorder |
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| 5:30 p.m. | Adjourn |
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| 7:00 p.m. | Optional Group Dinner Alfio's, 4515 Willard Avenue, Chevy Chase |
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| Tuesday, March 11 |
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| Chair, Day 2 Peter Jensen, M.D. |
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| Data Presentations |
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| 9:00 a.m. | Controlled study of prepubertal bipolar disorder Barbara Geller, M.D., Washington University |
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| 9:25 a.m. | Discussion |
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| 9:40 a.m. | Overlap of bipolar disorder and ADHD Joseph Biederman, M.D., Massachusetts General Hospital |
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| 10:15 a.m. | Discussion |
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| 10:45 a.m. | Young referred boys with DICA-P diagnoses of mania: CBCL profiles
and comorbid disorders Gabrielle Carlson, M.D., Jan Loney, Ph.D., Helen Salisbury, Robert Volpe, Mary Ferguson, and Todd Lefkowitz, SUNY at Stony Brook |
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| 11:10 a.m. | Discussion |
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| 11:25 a.m. | Young referred boys with DICA-P diagnoses of mania: Observed
behavior Jan Loney, Ph.D., Gabrielle Carlson, M.D., Helen Salisbury, Robert Volpe, Mary Ferguson, and Todd Kashdan, SUNY at Stony Brook |
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| 11:50 a.m. | Discussion |
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| 12:05 p.m. | Check-Out and Working Lunch |
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| 1:05 p.m. | Premorbid functioning in adolescent onset bipolar disorder Stan Kutcher, M.D., Dalhousie University, Halifax, Nova Scotia |
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| 1:30 p.m. | Discussion |
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| 1:45 p.m. | Juvenile Bipolar Disease: Course, genetics, and therapeutics Michael Strober, Ph.D., UCLA |
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| 2:10 p.m. | Discussion |
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| 2:25 p.m. | General Discussion of Data (and Case) Presentations Where are the gaps? |
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| 3:10 p.m. | Overall Wrap-Up Discussion Research agenda for early-onset bipolar disorder: Next steps Research dissemination |
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| 4:00 p.m. | Adjourn |
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Other Materials
Journal of Affective Disorders 51 (1998) 75-76
Editorial
The childhood roots of bipolar disorder
This November issue is dedicated to the proceedings of a 1997 conference on childhood bipolarity that took place at the National Institute of Mental Health, Bethesda. This conference and its predecessor, which took place in 1993, also under the auspices of the National Institute of Mental Health, represent landmarks in clinical research on the childhood origins of bipolar disorder. This issue addresses at great length and in depth the diagnostic dilemmas involved, especially confounding boundary problems with attention deficit hyperactivity and conduct disorders. Although treatment was not the main focus of the conference, the use of lithium and mood stabilizers does receive some attention.
Is bipolar disorder recognizable in childhood? Are its manifestations "typical" and do they conform to the classical description of the illness in adults? The last question assumes that there is a classical picture in adult manic depression and that most patients conform to it. Clinical reality is otherwise: the diagnosis is made in adults only when clinicians look for the disorder and are able to observe it in spite of confounding personality, anxious and substance abuse comorbidity. I submit that the situation is analogous in childhood, with perhaps more boundary problems. This may be more apparent than real, because only more recently child clinicians have begun to take the task of diagnosis seriously. Nonetheless, developmental issues might lead to greater diagnostic challenges. These issues receive extensive consideration in light of research data generated by an elite group of child psychiatrists and psychologists, many of whom are pioneers in the emerging field of childhood bipolarity. They describe, in this issue, the psychotic excited stages of the illness, often with mixed and rapid cycling features. Euphoric episodic mania can be encountered, but is distinctly less prevalent than the former more erratic dysphoric picture.
As an adult psychiatrist working in a mood clinic, I was privileged to listen to mothers who often complained that their children exhibited affective, behavioral, and rhythm problems that neither pediatricians nor child clinicians took seriously (Akiskal et al., 1985). What they described in their children paralleled their own experience: extreme fluctuating temperamentality, moodiness, instability, unexplained intermittent periods of depression, philosophical brooding about life and death, sudden suicidal urges, irregularities in sleep, appetite and sexual drives (including dating), unevenness in school performance and social life; many were talented, but dilettantes at best. As Kraepelin had described a century ago, these temperamental features often preceded by years more discrete episodes, but could also exist in the absence of the major episode manifestations of manic depressive illness. Like most diseases of mankind, bipolar manifestations characteristically arise imperceptibly from a background of what, in retrospect, appear to be at the one extreme end of the normal. "Explosive" onsets are often superimposed, again largely in retrospect, on such a prepared ground. In medical psychology, temperament is the concept that refers to genetically determined emotional response biases that provide such a predisposing terrain for affective disorders. The genetics of the major affective disorders, including bipolar disorders, might largely coincide with the polygenic inheritance of affective temperamental traits. A major challenge for child psychiatry is to describe how development impacts on the phenotypic expression of the genetic liability to temperamental moodiness. One of the advantages of this conceptual framework to understanding the development of childhood bipolarity is that predisposing temperament and clinical manifestations of affective illness represent a continuum. Both are described in affective language: affective traits, which represent extremes on a continuum with normality on the one hand, merge with the affective symptoms and behavioral disturbances of the clinical syndromes.
This issue is dedicated to one of the giants of child psychiatry in the modern era: Dennis Cantwell, who died a few weeks after attending this conference. At this conference I had the privilege to present a paper on the putative temperamental foundations of bipolar disorder in juvenile subjects. It is with a mixture of fond memories and sadness that I write these lines, as I reminisce about what proved to be my last conversation with Denny. Actually, he subsequently wrote me a brief note, expressing his interest to collaborate on the use of our affective temperament instrument in the study of juvenile bipolarity. That is in part the excuse for publishing in the present issue a special article, in which my Italian collaborators and I explore questions on the very stability of these temperamental measures in juvenile subjects in a non-patient population.
The question of temperament provides a bridge with the previous issue of the Journal of Affective Disorders (October, 1998) which was entirely dedicated to the role of personality factors in mood disorders.
References
Akiskal, H.S., Downs, J., Jordan, P., et al., 1985. Affective disorders in the referred children and younger siblings of manic-depressives: Mode of onset and prospective course. Arch gen Psychiatry. 42, 996-1003.
Hagop S. Akiskal, M.D.
University of California at San Diego
VA Psychiatry Service (116A)
3350 La Jolla Village Drive
San Diego, CA 92161 USA
Tel: 619-552-8585, x2226
Fax: 619-534-8598
E-Mail: hakiskal @ucsd.edu
Journal of Affective Disorders 51 (1998) 77-80
Introduction
Current issues in childhood bipolarity
Introduction
Current issues in childhood bipolarity
Editha D. Nottelmann (corresponding author: tel +1-301-443-9734; e-mail enottelm@nih.gov),
Peter S. Jensen, NIMH, 5600 Fishers Lane, Room 18C-17, Rockville, MD 20857, USA
Dedication: We dedicate this special issue to Dennis P. Cantwell, M.D. (1939-1997). Dr. Cantwell, who participated in the workshop on which this special issue is based, had also planned to contribute a paper. He died on 14 April 1997, shortly after many of us met him for the last time on March 10th and 11th. We continue to miss him.
1. Introduction
Five years ago the National Institute of Mental Health (NIMH) held a workshop on bipolar affective disorder in children and adolescents. Its purpose was to begin to explore, in the context of a life-span perspective, what is known about bipolarity in children and adolescents and to set directions for future research. Papers based on that meeting were published in a special section of the Journal of the American Academy of Child and Adolescent Psychiatry (vol. 34 (6), pp. 705-763).
With support from the National Institutes of Health (NIH) Office of Rare Diseases, the NIMH recently (March 1997) convened another workshop focusing on bipolar disorder in children. Its purpose was to bring together clinical researchers who study mood disorders in young children and to examine and discuss assessment phenomenology, diagnosis, and treatment of prepubertal bipolar disorder. Although still controversial, the emerging thinking in North America is that manic symptoms seen prior to adolescence or mid-puberty are a manifestation of an early onset form of bipolar disorder (cf. Geller and Luby, 1997). Most notably, prepubertal bipolar disorder is being diagnosed with increasing frequency in children who also have a diagnosis of attention deficit hyperactivity disorder (ADHD).
Support for the workshop from the NIH Office of Rare Diseases reflects the fact that early onset bipolar disorder, extrapolating from our best estimates for all depressive disorders, has a very low prevalence rate. From community studies we know that the rate of depressive disorders in children and adolescents ranges from 1.8 to 13.3%; in most studies, the rates are below 5% (Nottelmann and Jensen, 1995a). As the number of depressed subjects in any individual study tends to be small and confidence intervals around the prevalence estimates, in consequence, to be wide, the rate of depression in the general population of children and adolescents, in fact, has been estimated to be as low as 2-3% (Angold and Costello, 1995). Bipolar disorder occurs at a much lower rate. For ADHD, community study prevalence rates for children and adolescents tend to be higher, ranging from 0.2 to 17.1%; in most studies, they are below 11% (Nottelmann and Jensen, 1995a). Using rates on the conservative side for depressive disorders and ADHD of 5 and 11%, as well as on the high side of 13.3 and 17.1%, respectively, the expected rate of comorbidity between depressive disorders and ADHD, therefore, should be between 0.5 and 2.3% (see Caron and Rutter, 1991). The comorbidity rate between bipolar disorder and ADHD should be a vanishingly small fraction at the low end of that range. It is one of the issues in the ongoing controversy surrounding assessment, phenomenology, diagnosis and treatment of prepubertal bipolar disorder. Not at issue, as the following papers indicate, is that children who present with manic symptoms are seriously ill, whether in the context of ADHD or of other psychiatric disorders.
Discussion of symptoms of prepubertal mania was informed by presentations by Hagop Akiskal, Joseph Biederman, Dennis Cantwell, Gabrielle Carlson, Pamela Cole, Barbara Geller, Stan Kutcher, Jan Loney, Melvin McInnis, Michael Potegal, Adelita Segovia, Michael Strober, and Elizabeth Weller. The papers included in this special issue cover most of the proceedings of the workshop. Five papers compare children with ADHD with children with manic symptoms: three (Biederman et al.; two by Geller et al.) present how they differ from each other; two (Carlson et al.; Carlson; Loney et al.) also examine these differences in the context of comorbidities with other externalizing disorders. The data presented by Kutcher et al. suggest that the majority of youngsters with adolescent-onset bipolar disorder, in contrast to children with earlier onset of symptoms of mania, have had good premorbid functioning. Finally, three papers report on lithium treatment: Geller et al., of prepubertal children with depression, considered at risk for bipolar disorder because of their family history; Kafantaris et al. and Strober et al., of bipolar adolescents with and without a childhood psychiatric history. Following these papers, Carlson provides an overview of issues specific to juvenile bipolar disorder and commentary on issues raised by this collection of papers. In part, it reflects the discussions that were held at the workshop. In addition to data-based presentations, case reports were made at the meeting, and two case reports are appended.
The research recommendations resulting from the earlier workshop on bipolar disorder continue to be relevant (Nottelmann and Jensen, 1995b). Directions for future research that specifically apply to investigations of prepubertal mania, resulting from last year's workshop, are summarized below. Predominant are assessment issues, including the need for new diagnostic criteria, for new measures of factors that affect children's functioning as well as for children's functioning itself, and for new instruments that discriminate ADHD from bipolar disorder. Also discussed was the need for treatment, genetic, and biologic studies.
1.1. Diagnostic criteria
It is seen as essential that the diagnosis of prepubertal bipolar disorder is made only by the most experienced clinicians. A distinction should be made between bipolar I and bipolar II. Lifetime diagnosis is critical, and templates or prototype narratives, in addition to ascertainment of presence or absence of symptoms, should be the best tools for obtaining useful information about onset, 'course,' 'episode,' and 'cycle' and their relation to comorbid disorders and environmental influences. The question was raised whether it would be useful to create a bipolar III subcategory for prepubertal illness with less distinct episodes than more typically seen in postpubertal adolescence and adulthood.
1.2. Measures of child and family functioning
There was general agreement that it is not enough to assess children's symptomatology, but that we need to learn more about children's general functioning and about the socioenvironmental context in which they are being raised. Children's functioning should be assessed in multiple domains and in multiple settings with multiple methods. Nonstandard methods include, for example, the use of actimeters and time sampling for behavioral observations. Risk and protective factors need to be explored. Family assessment should go beyond diagnostic family histories. Current family functioning and the amount of care that family members are receiving are important as well. Substance use disorders should be documented.
1.3. Discrimination of other psychopathology from bipolar disorder
A need was expressed for better tools for discriminating ADH from bipolar disorder: rating scales with non-overlapping symptomatology. Geller et al. have begun the process by adding to the K-SADS items for the assessment of mania (cf. their paper on prepubertal and young adolescent bipolarity versus ADHD, this volume). A new instrument, Childrens' Interview for Psychiatric Syndromes (ChIPS), developed by the Weller team (Fristad et al., submitted, a,b,c; Rooney et al., submitted, a,b) which has a child as well as a parent version, holds promise for discriminating between ADHD and mania by providing non-overlapping questions. These instruments will, of course, need to distinguish mania from other disorders in which mood elements are a significant feature. While ADHD is most conspicuous in this respect, other disorders and even 'normal' emotionality need to be discriminated. In the latter instance, child-friendly dimensional scales should be developed for mood lability, as they have been for depression and ADHD.
1.4. Biological and treatment studies
There is a dearth of good basic psychopharmacological studies on early onset bipolar disorder. Pharmacological dissection provides one approach to validating diagnoses from outside the diagnostic system; anatomical and functional neuro-imaging may furnish another for making differential diagnoses and breaking out meaningful subgroups (cf. Cantwell, 1995; Jensen et al., 1997). The advantage of doing biological and treatment studies in children and adolescents is that they are less likely to have 'scars' from long-term use of medication or a long-term course of illness. As it is extremely difficult to do double-blind placebo-controlled studies with severely ill children, open label or contrasting treatment studies should be considered. It was suggested that it would be useful first to examine systematically in children the pharmacological agents that work in adults, dosing properly, following through carefully, tracking side effects and symptoms and outcome. Then unique treatments, including 5HT2D agents, should be examined to find out if they have more promise. There was mention also of a study of thyroid indices in bipolar adolescents that had findings similar to studies in adults and that biological studies like that should also be done with children. To be addressed longitudinally is the question of whether what occurs biologically and genetically changes during development, as certain biological systems and/or genes are activated or inactivated.
1.5. Genetic studies
As the social environment has a large role in the lives of children, genetic studies should include examination of environmental as well as genetic factors. In addition to the study of families of child probands, and an understanding of child psychopathology in adults with bipolar disorder, it should be useful to piggyback onto existing studies of adult bipolar probands by studying their offspring. Another genetic study strategy would be to collect data on siblings. Important in such studies would be to use a dimensional approach in the assessment of symptoms in order to identify cases that do not meet criteria for diagnoses, but are likely to do so at a later follow-up period.
In a sense, for childhood bipolar disorder, we stand at the threshold of a major period of scientific growth, search, and discovery. This is a time of excitement and the opening of new vistas, which in many ways harkens back to the late 1960s/early 1970s, when our field began to look with fresh eyes (sharpened by studies of adults) at the phenomenon of depression in children. Unfortunately, it took a long period of research and discovery--almost three decades--to win general acceptance of the phenomenon of childhood depression among researchers and clinicians (though there may still be a few skeptical hold-outs in the general health sector). As clinicians and scientists, we can diagnose it reliably and, most importantly, mounting data suggest that we can treat and prevent it. Even sectors of the general public are increasingly eager to understand childhood depression and embrace more sophisticated, evidentiary-based approaches to its diagnosis and treatment.
As this special section attests, with prepubertal bipolar disorder, we have a much better headstart than we did with major depression in childhood. After three decades of public health investments in research and discovery, we now have (1) more open minds to the possibilities of serious childhood psychiatric illnesses, (2) better diagnostic instruments, (3) new neuroscientific and statistical tools, and (4) more sophisticated research questions, all of which can and should be employed to examine the vexing problems surrounding childhood bipolar disorder. So, as readers and writers alike for this special section, we can say we were there "for the kickoff." Given this head start, is it too much for us to expect a few 'touchdowns' within a single decade?
References
Angoid, A., Costello, E.J., 1995. The epidemiology of depression in children and adolescents. In: Goodyer, I.M. (Ed.), The Depressed Child and Adolescent: Developmental and Clinical Perspectives. Cambridge University Press, Cambridge, pp.127-147.
Cantwell, D.P., 1995. Child psychiatry: introduction and overview. In: Kaplan, H.I., Sadock, B.J. (Eds.), Comprehensive Textbook of Psychiatry/IV. Williams & Wilkins, Baltimore, MD, pp. 2151-2154.
Caron, C., Rutter, M., 1991. Comorbidity in child psychopathology: Concepts, issues and research strategies. J. Child Psychol. Psychiatry 32, 1063-1080.
Fristad, M.A., Rooney, M.T., Weller, E.B., Weller, R.A., Salmon, P. Study III: Reliability and validity of the P-ChIPS (Childen's Interview for Psychiatric Syndromes--Parent Version) (in press).
Fristad, M.A., Cummins, J., Verducci, J.S., Rooney, M.T., Weller, E.B., Weller, R.A. Study IV: Children's Interview for Psychiatric Syndromes (ChIPS)--Revised Psychometrics for DSM-IV (in press).
Fristad, M.A., Glickman, A.R., Verducci, J.S., Teare, M., Weller, E.B., Weller R.A. Study V: Children's Interview for Psychiatric Syndromes (ChIPS)--Psychometrics in two community samples (in press).
Geller, B., Luby, J., 1997. Child and adolescent bipolar disorder: Review of the past 10 years. J. Am. Acad. Child Adolesc. Psychiatry 36, 1168-1176.
Jensen, P.S., Martin, D., Cantwell, D.P., 1997. Comorbidity in ADHD: Implications for research, practice, and DSM-V. J. Am. Acad. Child Adolesc. Psychiatry 36, 1065-1079.
Nottelmann, E.D., Jensen, P.S., 1995a. Comorbidity of disorders in children and adolescents: Developmental perspectives. In: Ollendick, T.H., Prinz, R.J. (Eds.), Advances in Clinical Child Psychology, vol. 17. Plenum Press, New York, pp. 109-155.
Nottelmann, E.D., Jensen, P.S., 1995. Introduction (Special Section, 'Bipolar Affective Disorder in Children and Adolescents'). J. Am. Acad. Child Adolesc. Psychiatry 34, 705-708.
Rooney, M.T., Fristad, M.A., Weller, E.B., Weller, R.A., Salmon, P. Study I: Development and criterion validity of ChIPS (Children's Interview for Psychiatric Syndromes) (in press)
Rooney, M.T., Fristad, M.A., Weller, E.B., Weller, R.A., Salmon, P. Study II: Reliability and validity of the DSM-III-R ChIPS (Children's Interview for Psychiatric Syndromes) (in press).
The Journal of Affective Disorders Special Issue on Current Issues in Childhood Bipolarity is on file in the Office of Rare Diseases. It can also be obtained from any library and from the National Institute of Mental Health, Drs. Editha D. Nottelmann and Peter S. Jensen, 5600 Fisher Lane, Room 18C-17, Rockville, MD 20857.
