The Psychobiology of Childhood: A Profile of Current Issues PDF
Preview The Psychobiology of Childhood: A Profile of Current Issues
The Psychobiology of Childhood The Psychobiology of Childhood A Profile of Current Issues Edited by Laurence L. Greenhill, M.D. Assistant Professor of Psychiatry Columbia University College of Physicians and Surgeons New York, New York Baron Shopsin, M.D. Associate Clinical Professor of Psychiatry New York University School of Medicine New York, New York MTP!!it'MITED International Medical Publisher Published in the UK and Europe by MTP Press Limited Falcon House Lancaster, England Published in the US by SPECTRUM PUBLICATIONS, INC. 175-20 Wexford Terrace Jamaica, NY 11432 Copyright © 1984 by Spectrum Publications, Inc. Softcover reprint of the hardcover 1st edition 1984 All rights reserved. No part of this book may be reproduced in any form, by photostat, microfilm, retrieval system, or any other means without prior written permission of the copyright holder or his licensee. ISBN-13: 978-94-011-6703-1 e-ISBN-13: 978-94-011-6701-7 DOl: 10.1007/978-94-011-6701-7 Contributors Michael G. Arnan, Ph.D .• MRC Senior Research Fellow, Department of Psychiatry, University of Auckland, New Zealand George M. Anderson, Ph.D .• Assistant Professor of Laboratory Medi cine, Yale University School of Medicine, New Haven, Connecticut Gerald L. Brown, M.D .• Staff Psychiatrist, Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland Dennis P. Cantwell, M.D .• Joseph-Campbell Professor of Child Psychiatry and Director of Residency Training in Child Psychiatry, Uni versity of California School of Medicine, Neuropsychiatric Institute, Los Angeles, California Donald J. Cohen, M.D. • Professor of Pediatrics and Psychiatry, Yale University, New Haven, Connecticut Michael H. Ebert, M.D .• Chief, Section on Experimental Therapeutics, Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Maryland John C. Fletcher, Ph.D .• Assistant for Bioethics, Office of the Director, Clinical Center, National Institutes of Health, Bethesda, Maryland Rachel Gittelman, Ph.D .• Director of Clinical Psychology, Psychiatric Institute, New York City; Professor of Clinical Psychology, Columbia College of Physicians and Surgeons, New York, New York Laurence L. Greenhill, M.D .• Assistant Professor of Psychiatry, Colum bia College of Physicians and Surgeons, New York, New York v vi PSYCHOBIOLOGY OF CHILDHOOD C.R. Lake, M.D., Ph.D .• Professor of Psychiatry and Phannacology, United Health Service, Bethesda, Maryland Dennis H. Langer, M.D., L.L.B .• Clinical Associate, Unit on Child hood Mental Illness, Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland Morton Levitt, Ph.D .• Research Scientist, Columbia College of Physi cians and Surgeons, New York, New York Jeffrey A. Mattes, M.D .• Research and Staff Psychiatrist, Carrier Foundation, Belle Mead, New Jersey; Assistant Clinical Professor of Psychiatry, UMD-Rutgers Medical School, Piscataway, New Jersey Linda E. Nee, M.S.W .• Clinical Research Social Worker, Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Maryland Judith L. Rapoport, M.D .• Chief, Section on Child Psychiatry, Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Maryland Bennett A. Shaywitz, M.D .• Director and Associate Professor, Depart ment of Pediatric Neurology, Yale University School of Medicine, New Haven, Connecticut Jovan Simeon, M.D .• Professor and Director, Child Psychiatry Research, Royal Ottawa Hospital, Ottawa, Ontario, Canada David A. Smith, M.D .• Resident, Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, North Carolina Herbert Weingartner, Ph.D .• Chief, Unit on Cognitive Studies, National Institute of Mental Health, Bethesda, Maryland Gabrielle Weiss, M.D .• Professor of Psychiatry, McGill University, Montreal Children's Hospital, Montreal, Quebec, Canada John S. Werry, M.D .• Professor of Psychiatry, University of Auckland, New Zealand J. Gerald Young, M.D .• Professor and Director of Child Psychiatry, Mt. Sinai Hospital, New York, New York Preface This volume was inspired by an annual meeting of the American Col lege of N europsychopharmacology held in Maui, Hawaii. A panel on psychobiological issues of childhood was held, with presentations devoted to antidepressant drug levels in depressed prepubertal children, re sponses of normal and hyperactive children to stimulant medication, and the vulnerability of the adolescent offspring of manic-depressive parents to affective illnesses. The session drew a large crowd, and it seemed appropriate to develop these topics in a book. Many of the authors in this volume attended that conference, and the book reflects the fact that psychobiological research in children has moved even further along than was envisioned at Maui. In keeping with developments in the field, this volume surveys key topics of interest, including nosological issues surrounding the attention deficit disorder of childhood, the ontology of neurotransmitter systems in the human brain, and the relation between child psychiatric disorders and sleep patterns. Other studies link the clinical effects of drugs with plasma DBH activity or with attentional measures. The side effects of drugs on growth are examined, as well as the ethical issues involved in doing research on children. These areas continue to be of vital interest. The first chapter in this book examines the concept of the hyperactive syndrome, or the Attention Deficit Disorder of Childhood. Gabrielle Weiss is critical of the medical model of the disorder, feeling that it fails to include vital social-interactive effects of this syndrome, in particular, its prevalence, multiple etiologies, treatment responses, or outcome in adolescence or adult life. Dr. Weiss's perspective is unique, based on her classic follow-up studies of hyperactive children into adulthood. She advocates a broader biopsychosocial perspective. Dennis Cantwell further examines this theme in chapter 3, where he defends the medical model as an ideal tool for research in child psychia- vii viii PSYCHOBIOLOGY OF CHILDHOOD try. He subdivides this approach into six phases, including clinical de scription, physical and neurological factors, laboratory studies, family studies, longitudinal natural history studies, and treatment studies. He then outlines an ideal study whose goal is the identification of diagnosti cally homogeneous subgroups within the broader definition of the Atten tion Deficit Disorder of Childhood. In so doing, Cantwell provides an excellent review and update of this field. He shows the reader how the six stages of medical model interact, as for example the drug responsiveness of a particular group seems to be linked to a particular type of visual evoked response pattern, suggesting a neurodevelopmentavetiology for this subgroup. Such conceptualization provides valuable cross-pollination for the development of new understandings in the field. Langer and his colleagues examine ethical issues in child research in chapter 2. Complexities arise in this area that researchers have not encountered previously. At what age can a child give assent to a proce dure, and when should his signature be obtained on a consent form as well as his parent's? Langer advocates research with child subjects, but only after a careful weighing of benefits against risk and the approval of a group of peer investigators on an institutional review board (IRB). The five recommendations of the American Academy of Pediatrics Commit tee on Drugs are reviewed in detail, including methods for determining benefits and risk, proper selection of subject groups and representative individuals for research, the methods for obtaining informed consent (here Langer suggests thirteen is the proper age for getting signed informed consent), the rules for payment for participation in research, withdrawal from the study, and the use of proper monitoring and follow up studies. This approach should provide an invaluable reference on ethics and the proper protection of human subjects for the investigator starting out in research in Pediatric Psychiatry. Gerald Young and associates take up a number of basic developmen tal issues in chapter 4, which concerns itself with a thorough review of the ontogeny of human central nervous system neurotransmitter sys tems. Patterns of increasing and decreasing neurotransmitter activity characterize the human brain throughout life, with serum DBH and NE increasing and DA decreasing. Receptor function and hormonal modula tion of the central nervous system throughout life is also outlined. In addition, certain psychopathological states such as pervasive develop mental disorder (autism) are examined to determine deviations in neuro transmitter ontogeny. The reader is also provided with a brief review of neurotransmitter studies related to sex differences and to the response to psychotropic medication. All in all, Dr. Young's chapter, with its 8 pages PREFACE ix of references, will be a valuable resource for the student and experienced researcher alike. Chapter 5 introduces a new research tool in child psychiatry, the polysomnographic recording of sleep stages and behaviors. Simeon pro vides a brief but comprehensive overview of the developmental phases of human sleep, from infancy through senescence, with an emphasis on childhood. Sleep patterns in children with associated psychological and neurological disorders are also reviewed. Parasomnias, both those consid ered developmental and those pathological, are examined. The chapter ends with an overview of his extensive work with child population, including parental surveys of disturbed sleep in child clinical popula tions, including hyperkinetic males, and in childhood psychosis. The effect of various psychotropic agents on sleep patterns is described in words and graphs. Herbert Weingartner provides a theoretical chapter which discusses psychobiological methods to assess altered cognitive processes in chil dren. There is an excellent section on cognitive models, which empha sizes methods to assess speed and accuracy of information processing in children by testing efficiency of retrieval of information from memory. Cognitive tracking has become a major feature of many pediatric research projects, particularly in pediatric psychopharmacology, where various drugs (both stimulants and neuroleptics) may impair certain aspects of classroom learning through modulation of cognitive processes in children. Another side effect of long-term stimulant medication, growth inhi bition, is reviewed by this author in chapter 7. The complex methodology necessary to reliably collect and analyze growth data is examined, both in the chapter and a 5 page table that summarizes many of the studies in the field. An attempt is made to generate cross-study comparisons via a new index term, % expected velocity, to show the variable effects on growth determined by dosage and specific drug types. Etiological theo ries on the mechanism behind the stimulant-related growth inhibition are reviewed and the somatomedin hypothesis is suggested as the cause of the disorder. The remainder of the book is devoted to three pediatric psycho pharmacology studies which test basic hypotheses. Chapter 8, written by Mattes, Gittelman and Levitt, describes an attempted replication of an early Rapoport study which suggested a strong correlation of minor physical anomalies, high serum DBH levels, history of hyperactivity in the father, and an increased rate of obstetrical complications. This would be an important theoretical finding, since it would strongly implicate a x PSYCHOBIOLOGY OF CHILDHOOD problem in early development that could be linked to a genetic etiology. The disorder's phenotypic expression produces high DBH levels, thereby lowering brain norepinephrine, resulting in hyperactivity. Mattes and his colleagues compared a group of hyperactive males to a group with reading disorders, on and off methylphenidate, in a controlled, double blind design. Although the hyperactive children had significantly lower serum DBH than did their siblings, none of the associations suggested by the earlier Rapoport paper could be replicated, Werry and Aman tackle another thorny issue in the psychobiological field, namely the concept that hyperactive children show a diagnostically specific, "paradoxical" calming response to stimulants, while other types of children show arousal. A double-blind, counterbalanced study of methylphenidate was carried out in hyperactive males and a control group consisting of eneuretic males free of psychiatric disorder. These investigators were able to measure the direction of response, and their analytic methods allowed for interactive effects between group and drug to be quantitatively assessed. The paradoxical hypothesis would predict differing directions of response. The results showed both groups re sponded in identical directions on behavioral, clinical, and cognitive measures, although the hyperactive group responded in a greater manner to the same dose of stimulants than did the eneuretics. The authors conclude that the concept of paradoxical response to stimulants could not be supported by their data. The exaggerated response of the hyperactive group may be due to the law of initial values or to a new principle, that of rate-dependency in response to pharmacological agents. The book ends with an important theoretical chapter by Judith Rapoport's research team at the NIMH clinical center in Bethesda, Mary land. Basically, the authors tested the hypothesis that attention deficit disorders may be related to deficiencies in central noradrenergic sys tems. Mianserin hydrochloride, a drug that increases norepinephrine turnover in the central nervous system by inhibiting presynaptic alpha adrenergic receptors, was given to a group of 5 hyperactive males, in a double-blind, parallel design, with a group of 5 other hyperactives treated with placebo. Dependent measures included teacher's reports, motor activity, sustained attention, memory and learning tasks, blood pressure and pulse, urinary MHPG and VMA concentrations and plasma NE levels. The children on Mianserin experienced a number of moderate to severe side effects, including oversedation and hypotension with minimal changes on other measures. The authors concluded that Mianserin's effects were not evident in changes in behavior or cognition. This drug produces very slow changes in NE concentrations in the syn- PREFACE xi aptic cleft, and another agent, that produced immediate increases in NE, might be more successful in ameliorating the attention deficit disorder of childhood. These research topics reflect the recent upsurge in interest in biolog ical aspects of child mental disorders. The benefits of stimulants in ADDH, of clonodine in Tourette's syndrome, and of imipramine in pre pubertal depressions have been the result of psychobiological research in childhood. This growing field represents a powerful new course for those interested in child development, child psychopathology, and basic neuro SCIence. February, 1984 Laurence L. Greenhill, M.D. N.Y., N.Y.
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