Book Review

Neurobiology of Mental Illness

N Engl J Med 2000; 342:1617-1618May 25, 2000

Article

Neurobiology of Mental Illness
Edited by Dennis S. Charney, Eric J. Nestler, and Benjamin S. Bunney. 958 pp., illustrated. New York, Oxford University Press, 1999. $150. ISBN: 0-19-511265-2

I recently picked up a copy of the two-volume, multiauthored American Handbook of Psychiatry (Silvano Arieti, ed. New York, Basic Books), published in 1959. Neurobiology was represented only in a few sections, notably in one entitled Organic Conditions, which included discussions of neurosyphilis, dementia, epilepsy, behavioral disorders after brain lesions, Huntington's disease, and mental retardation. The so-called functional disorders (schizophrenia, affective disorders, and anxiety disorders) were examined in great detail, but there was little regarding abnormalities of the brain. Many varieties of psychotherapy were referred to as primary methods of treatment. The list of “physical therapies” included insulin shock, convulsive shock, and psychosurgery, with one chapter on drug therapy.

Few fields in medicine have experienced such a change in the underlying model of illness and treatment as did clinical psychiatry in the last part of the 20th century. Primary reasons for this development included the following: the overwhelming evidence of the efficacy of pharmacologic treatments, a growing appreciation of the heritability of psychiatric disorders, the standard use of objective, criterion-based diagnoses, and the ability to examine the structure and function of the brain directly.

All these factors are in evidence in Neurobiology of Mental Illness. Over 100 authors from 44 institutions are represented. The editors chose not to do an exhaustive survey of diagnoses but to focus on psychoses, mood disorders, anxiety disorders, substance-abuse disorders, childhood disorders, and dementia. This was a wise decision, since these are clearly the major causes of psychiatric disability and each has spawned a voluminous literature. Specific chapters are also devoted to special topics such as aggression, sexuality, eating disorders, personality disorders, and sleep disorders, and sections on basic and clinical investigative methods are included. The absence of the mention of somatoform disorders or disorders of impulse control does not seem to be an important omission. It is perhaps of more concern that no attention is given to the subject of mental retardation, since the molecular events underlying the fragile X syndrome (one of the increasing list of neuropsychiatric disorders associated with expanded trinucleotide repeats) are now well understood, and other specific syndromes associated with cognitive deficits (such as Down's syndrome, velocardiofacial syndrome, and Prader–Willi syndrome) are of increasing theoretical and practical interest.

Dementia is well covered, with 11 chapters on topics ranging from diagnostic schemes to animal models. Sherrington's review of molecular biology summarizes the three specific genes (on chromosomes 1, 14, and 21) that cause early-onset Alzheimer's disease and the apolipoprotein vulnerability factor on chromosome 19 (incorrectly referred to as causative in the conclusion). All the genes thus far identified appear to affect the processing of amyloid, which may be a final common pathway for these disorders. De Leon's review of neuropathology and neuroimaging includes a rationale for the use of magnetic resonance imaging in clinical diagnosis and even for the use of presymptomatic testing on the basis of a finding of hippocampal atrophy. The subsequent chapter on functional imaging by Buchsbaum and Hazlett emphasizes frontal- and temporal-cortex involvement.

Schizophrenia is covered in eight chapters, beginning with Breier's historical overview of diagnostic classifications. Kendler's chapter on molecular genetics cites probable loci on 8p, 22q, and 6p, but does not cover more recent evidence of loci on 10p, 6q, and 13q. It can reasonably be argued that all these data are tentative until an actual mutation is found. Bunney and Bunney review data on neuropathology, neuroimaging, and developmental biology to provide a coherent basis for the much-discussed neurodevelopmental hypothesis of schizophrenia. Berman and Weinberger relate frontal abnormalities to cognitive impairment and emotional blunting in schizophrenia, whereas temporal or limbic abnormalities may be related to delusions and hallucinations. Braff reviews the information-processing deficits in patients with schizophrenia, including abnormalities in smooth-pursuit eye tracking, continuous performance task deficits, prepulse inhibition, P300 event-related potentials, and the P50 gating deficit (which may be associated with variation in a nicotinic receptor gene). This deficit appears to reduce the ability of patients with schizophrenia to “filter” their environment and may make it difficult for them to assign proper priorities to incoming perceptions. Tamminga's principles of pharmacotherapy contrast atypical neuroleptic agents with haloperidol-like compounds, whose unquestioned efficacy was offset by their adverse effects.

Boland and Keller review the complex recent history of mood-disorder nosology, a field that is still evolving in consideration of the minor depressive disorders and their relation to the more severe and recurrent bipolar and unipolar disorders. Sanders covers the involvement of chromosomes 18p, 21q, and Xq26–28 in mood disorders, mentioning other areas as well. This chapter brings up a general issue: eight chapters in Neurobiology of Mental Illness are devoted to molecular biology and molecular genetics, each in a different section and by a different author. Thus, the excellent chapter by Alsobrook and Pauls on the molecular genetics of childhood psychiatric disorders begins with 3 1/2 pages of introductory material on linkage, association, and molecular techniques. This same material is covered by Gelernter in the introduction (and to a lesser extent in the chapters by Sanders and Kendler). The six imaging chapters seem to have been integrated more closely to avoid duplication. Some overlap is probably inevitable given the organization of the book, but it should be minimized in future editions.

I found the specific chapters in each section to be some of the most helpful. The section on anxiety disorders includes a chapter on the functional neuroanatomy of the amygdala (by Davis) and a separate chapter on the effects of stress on the hippocampus (by McEwen). The section on substance-abuse disorders contains a chapter on the effects of alcohol and cocaine on brain development (by Kosofsky), since as the author states, exposure to drugs is the single largest preventable cause of developmental problems in utero in our society. The section on dementia includes chapters on the neurobiology of learning and memory. Neurobiologic models of recurrence are covered in the section on mood disorders.

The authors are uniformly first rate. Though one could conceive of an edited version that would be less dependent on East Coast universities, it is hard to quibble with the choices that have been made here.

This is not a how-to book for diagnosis and treatment, nor should it be regarded as offering an overview of schools of thought in modern psychiatry. It is, rather, a reference book on the neurobiologic underpinnings of our concepts of psychiatric illness. It should find a place on the shelf of practitioners in mental health–related fields, since it will help them interpret the reports they will see in the future on genetic and neuroanatomical abnormalities in their patients. It will be of interest to physicians in other specialties who may wonder about the rationale for the use of anticonvulsants in patients with mood disorders, the interpretation of abnormalities on magnetic resonance imaging scans in patients with schizophrenia, or the use of the sleep laboratory in differential diagnosis. Teachers of clinical and basic neuroscience will use this book to convey the relevance of laboratory-derived concepts and methods to public health and human behavior. The discipline described here is a far cry from the psychiatry we grew up with. Sigmund Freud, a neurobiologist by training, would have been proud.

J.I. Nurnberger, Jr., M.D., Ph.D.
Indiana University School of Medicine, Indianapolis, IN 46202-4887