The Thyroid Axis and Psychiatric Illness 0880483644, 9780880483643

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The Thyroid Axis and Psychiatric Dlness Edited by Russell T. Joffe, M.D., and Anthony]. Levitt, M.D. This book assembles the latest information about the relationship between thyroid state and behavior. It is intended to serve as a reference for both the basic scientist and the clinician in the field of psychiatry and the behavioral sciences.

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The Thyroid Axis and Psychiatric Rlness also presents the controversies, ambiguities, and unanswered questions that will be left to the future to resolve. This book not only provides information about the role of the thyroid axis in psychiatric illness, it is also designed to promote further research and understanding of this complex subject.

RUSSELL T. JOFFE, M.D. ANTHONY J. LEVITT, M.D.

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The Thyroid Axis and

Psychiatric Illness

The Thyroid Axis and

Psychiatric Illness

u....... dl T. Joffe, M.D. ~ 1• "HI I

isorders Program, Clarke Institute of Psychiatry .artd 1he University of Toronto, Toronto, Ontario, Canada

\ nlltony J. Levitt, M.D. I•H ad Di orders Program, Clarke Institute of Psychiatry .111d

1he

University of Toronto, Toronto, Ontario, Canada

Washington, DC London, England

Note: The authors have worked to ensure that all information in this book concerning drug dosages, schedules, and routes of administration is accurate as of the time of publication and consistent with standards set by the U.S. Food and Drug Administration and the general medical community. As medical research and practice advance, however, therapeutic standards may change. For this reason and because human and mechanical errors sometimes occur, we recommend that readers follow the advice of a physician who is directly involved in their care or the care of a member of their family. Books published by the American Psychiatric Press, Inc., represent the views and opinions of the individual authors and do not necessarily represent the policies and opinions of the Press or the American Psychiatric Association. Copyright © 1993 American Psychiatric Press, Inc. ALL RIGHTS RESERVED Manufactured in the United States of America on acid-free paper. 96 95 94 93 4 3 2 1 American Psychiatric Press, Inc. 1400 K Street, N.W., Washington, DC 20005 Library of Congress Cataloging-in-Publication Data The Thyroid axis and psychiatric illness I edited by Russell T. Joffe, Anthony J. Levitt. p. em. Includes bibliographical references and index. ISBN 0-88048-364-4 (alk. paper) 1. Hypothalamic-pituitary-thyroid axis-Diseases-Psychological aspects. 2. Thyroid gland-Diseases-Psychological aspects. 3. Mental illness-Endocrine aspects. 4. Psychoneuroendocrinology. I. Joffe, Russell T., 1954- . II. Levitt, Anthony J. , 1959- . [DNLM: 1. Mental Disorders-complications. 2. Thyroid Diseasescomplications. 3. Thyroid Gland-physiology. 4. Thyroid Hormonesphysiology. WK 202 T54665] RC455.4E54T49 1993 616.89-dc20 DNLM/DLC for Library of Congress 92-22046 CIP British Library Cataloguing in Publication Data A CIP record is available from the British Library.

For Jennifer and Lina

Contents

Contributors

IX

Foreword .. Arthur f. Prange, Jr., M.D.

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Preface . . . . . . . . . . . . . Russell T. Joffe, M.D., Anthony f. Levitt, M.D.

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PART 1: Basic Principles 1.

Cerebral Versus Peripheral Regulation and Utilization of Thyroid Hormones . . . . . . . . . . . . . . . . . . 1 Mary B. Dratman, M.D.

2.

Nutrition, Energy Metabolism, and Thyroid Hormones . . . . . 95 Anthony f. Levitt, M.D., Russell T. Joffe, M.D.

3.

Interactions Between Thyroid Hormones and Other Endocrine Systems . . . . . . . . Julio Licinio, M.D., Ma-Li Wong, M.D., Philip W Gold, M.D.

4.

. . . . . . . . . 133

The Hypothalamic-Pituitary-Thyroid Axis: Clinical and Theoretical Principles . . . . . . . . . . . . . . . . 147 Betty L. Chan, M.D., William Singer, M.D.

PART II: Clinical Principles 5.

Psychiatric Aspects of Thyroid Disease . . . . . . . . . . . . . . 171 Victor I. Reus, M.D.

6.

The Thyroid and Depression . . . . . . . . . . . . . . . . . . . . 195 Russell T. Joffe, M.D., Anthony f. Levitt, M.D.

7.

The Thyroid and Anxiety Disorders . . . . . . . . . . . . . . . . 255 Murray B. Stein, M.D., Thomas W Uhde, M.D.

8.

9.

10.

Interrelationships Between the Hypothalamic-Pituitary-Thyroid Axis and Alcoholism . . . . . 279 James C. Garbutt, M.D. , Peter T. Loosen, M.D., Arthur f. Prange, Jr., M.D. The Thyroid and Eating Disorders . . . . . . . . . . . . . . . . 297 Allan S. Kaplan, M.D., D. Blake Woodside, M.D. The Thyroid and Schizophrenia . . . . . . . . . . . . . . . . . . 317 Russell T. Joffe, M.D., Anthony]. Levitt, M.D.

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 327

Contributors

Betty L. Chan, M.D. I esident, Division of Endocrinology t. Michael's Hospital and the University of Toronto Toronto, Ontario, Canada Mary B. Dratman, M.D Professor, Department of Medicine Veteran's Administration Medical Center Philadelphia, Pennsylvania James C. Garbutt, M.D. Associate Professor, Department of Psychiatry and Center for Alcohol Studies University of North Carolina at Chapel Hill Director, Clinical Research Unit Dorothea Dix Hospital Raleigh, North Carolina Philip W. Gold, M.D. Chief, Clinical Neuroendocrinology Branch National Institute of Mental Health Bethesda, Maryland Russell T. Joffe, M.D., Head, Mood Disorders Program Clarke Institute of Psychiatry Associate Professor, Department of Psychiatry University of Toronto Toronto, Ontario, Canada

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The Thyroid Axis and Psychiatric Illness

Allan S. Kaplan, M.D. Director, Eating Disorders Centre, Toronto General Hospital Associate Professor, Department of Psychiatry University of Toronto Toronto, Ontario, Canada

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Anthony J. Levitt, M.D., Deputy Head, Mood Disorders Program Clarke Institute of Psychiatry Assistant Professor, Department of Psychiatry University of Toronto Toronto, Ontario, Canada Julio Licinio, M.D. Assistant Professor, Department of Psychiatry Yale University School of Medicine and West Haven Veteran's Affairs Medical Center West Haven, Connecticut Peter T. Loosen, M.D. Professor, Department of Psychiatry and Medicine Vanderbilt University Chief of Psychiatry, Veteran's Affairs Hospital Nashville, Tennessee Arthur J. Prange Jr., M.D. Boshamer Professor, Department of Psychiatry University of North Carolina at Chapel Hill Chapel Hill, North Carolina Victor I. Reus, M.D. Professor, Department of Psychiatry University of California, San Francisco School of Medicine San Francisco, California William Singer, M.D. Associate Professor, Division of Endocrinology St. Michael's Hospital Department of Medicine, University of Toronto Toronto, Ontario, Canada

ntributors

Murray B. Stein, M.D. 1\ sistant Professor, Department of Psychiatry and Pharmacology University of Manitoba Winnipeg, Manitoba, Canada Thomas W. Uhde, M.D. ' hief, S~ction on Anxiety and Affective Disorders Biological Psychiatry Branch National Institute of Mental Health lk thesda, Maryland Ma-Li Wong, M.D. Assistant Professor, Department of Psychiatry Yale University School of Medicine and West Haven Veteran's Affairs Medical Center West Haven, Connecticut D. Blake Woodside, M.D. taff Psychiatrist, Eating Disorders Centre 'lb ronto General Hospital Assistant Professor, Department of Psychiatry, University of Toronto Toronto, Ontario, Canada

Xl

Foreword

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hen Joffe and Levitt invited me to write a foreword for this book, I accepted with enthusiasm. As they note, 19 years have elapsed .im anyone attempted to assemble a coordinated series of statements dHJ ut the relationships between thyroid state and behavior. Although all 111 I crested people probably share the sense that remarkable progress has [u·,·n made, no one heretofore has surveyed it. I anticipated reading the 111 lllLLScript as an important aspect of my education, and I have not been .li~.1ppointed . I came away with more notes than could ever be incorpol.dcd into the paragraphs that follow and with more research ideas than , .111 I ikely be executed, let alone funded. 'I'he first four chapters of this book are basic, in two senses: they pertain 1', I>a ic science, and they provide a foundation for the six clinical chapters 1h.1t follow. Throughout the book, the authors have given careful attention In what is new and what is relevant to clinical issues, while maintaining l'''rspective about the many decades of psychothyroidology that have gone lwf ore. (Incidentally, if "psychothyroidology" is a neologism on my part, .o be it. I think its meaning is self-evident, and it is exactly what this book t·•• 1b ut.) In the first chapter, Dratman focuses on the details of thyroid transaclloliS as they can be studied in laboratory animals. The reader gains insight .11 the cellular and subcellular level and comes to realize the myriad points ,, t which the thyroid economy, of brain or of periphery, can be influenced. l'hl' brain, it seems, enjoys a series offail-safe systems. But do these brainf',ll.lrding and brain-sparing mechanisms always function without fault? I >1 .1tman thinks that, compared with other organs, the brain is exquisitely ·''"sitive to changes in thyroid economy when finally they occur. Indeed, 111 11conatallife, nothing can spare the brain the disaster of cretinism except 111 adequate supply of thyroid hormones from the infant's gland or from 11 a·d ication.

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The Thyroid Axis and Psychiatric Illness

Energy metabolism is as much a concern of clinical science as of basic science, and its consideration by Levitt and Joffe in Chapter 2 provides a graceful bridge between the basic principles chapters and the clinical principles chapters of this book. Although the case for studying energy balance in eating disorders would seem prima facie, the authors build a case for studying it in affective disorders as well. Just as in affective disorders, in matters of energy balance both thyroid hormones and catecholamines are involved, sometimes interactively. Thyroid state, it would seem, is poised between being a target of nutritional intake and an agent of energy expenditure. In the latter case, peripheral events seem to account for most observations. Thus whether a study of energy metabolism is more useful than other approaches in psychothyroidology remains uncertain, but surely the effort is justified. Licinio, Wong, and Gold broaden the perspective of the book when they take up the matter of interactions between the hypothalamic-pituitarythyroid (HPT) axis and other endocrine systems in Chapter 3. Attention to this is critically important to progress in psychothyroidology. To understand the thyroid state of a patient, however thoroughly it may have been described, we need two other orders of information: a sense of what went before in the thyroid axis (a plea for longitudinal studies) and a sense of the broader endocrine context. It is in patients with affective disorder that psychothyroidology so far has found its major place, and it is also in this group of patients that disturbances of the hypothalamic-pituitary-adrenal (HPA) axis are best described. It should not be astonishing, then, that the HPT and HPA axes are closely fitted, as Licinio and his colleagues show. But they are closely fitted, I think, not only at instants of time, but also across time. So far as I know, John Mason was the first to emphasize that, when experimental stress is prolonged, there occurs a sequence of responses by the organism: an autonomic response, an adrenal response, and finally a thyroidal response. In my view, it would be an error-surely not one committed by these authors-to think that the thyroidal response is less important for being delayed. It is probably chronic stress, not momentary danger, that produces changes of clinical significance. Licinio and his colleagues invite the reader's attention to relationships that otherwise might be overlooked. One is that the insulin response to ~-adrenergic agonists is a function of thyroid state. In a later chapter, Stein

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XV

111 d Vhde state, rightly I think, that there is a need for measures of tissue ' ' ·. ponse to thyroid hormones. Although several are known, what would lu 11! al is a measure of the response of brain, but we have no such measure, ''''ll's it is behavior itself. Lacking a dependent variable from brain that is ' ' .11 lily measured, one might do well to assess some response of a periph' 1. d t i sue that seems to have special pertinence to brain. In this way, the ""',ISurement of insulin response to a ~-adrenergic agonist has special ap1'' .11. Whybrow and I ( 1) once developed the view that thyroid-~-adrener1' 11 interactions might be especially important for brain and thus for lu h.1vior. < )verlapping somewhat with the Dratman chapter, as it should, Chapter I l1 y han and Singer strikes just the right note. The authors describe the I• ,,, ,,rkable advances in basic science that have permitted the clinical prog' ' '~ that, in turn, has made this book both necessary and useful. They pro' "''' a broad biological orientation. Thyroid glands are as characteristic of ··1t ebrates as are their back bones. Just as the thyroid economy of the brain 1 tt •gulated differently from that of the periphery, so may fetal (and neo11 ,11 .11 ) thyroid economy be different from that of the adult. The thyroid l'.i.IIHI possesses a huge storage capacity. One appreciates that with this .t 1tt t lure we vertebrates have found means not only of storing but