Book Review

Neurodevelopment and Schizophrenia

N Engl J Med 2005; 353:1638-1639October 13, 2005

Article

Neurodevelopment and Schizophrenia
Edited by Matcheri Keshavan, James Kennedy, and Robin Murray. 488 pp., illustrated. Cambridge, England, Cambridge University Press, 2004. $150. ISBN: 0-521-82331-5

This multiauthored book covers a broad range of topics related to neurodevelopment and psychosis. In its current form, the neurodevelopmental hypothesis of schizophrenia proposes that pathogenic mechanisms operate long before the first episode of psychosis, particularly before birth or during early postnatal life. The hypothesis has heuristic value, but it has proved to be difficult to test; the interpretation of some experimental results is controversial, and the lack of appropriate experimental design and replication has been a frequent problem. The hypothesis has also been criticized because of the long asymptomatic period between early development and the onset of psychosis — a distinguishing characteristic of schizophrenia. Some studies focus on whether the onset of psychosis can be predicted in prospective epidemiologic studies. Such studies are expensive, because schizophrenia develops in only a small proportion of the general population (approximately 1 percent). However, they do permit the analysis of the distribution of traits in the general population, which is not possible in studies only of persons at high risk for the disease, such as the study of the offspring of affected parents.

A key question is what the studies of the neurodevelopmental hypothesis can teach us about prevention and clinical practice. Infections, obstetrical complications, and prenatal malnutrition have been found to be associated with small increases in the risk of schizophrenia in some studies, and each factor constitutes a potential target for prevention. The result of severe dietary restriction in the western Netherlands during the winter of 1944–1945 (known as the “Dutch hunger winter” of the Nazi blockade of food supply to large Dutch cities) showed that famine can increase the risk of schizophrenia in the children of women who are pregnant at the time of the famine. An analogous result was also reported by St. Clair et al. (JAMA 2005;294:557-62), who studied the effect of prenatal exposure to the Chinese famine of 1959–1961 (this study was published after the publication of Neurodevelopment and Schizophrenia).

Will the cause of schizophrenia ultimately be reduced to factors at work during a critical developmental period? The answer is unknown, but recent studies indicating an increased risk of schizophrenia as a result of the use of cannabis suggest that some contributing factors are active after the early period of development (or even after development is complete). Furthermore, the largest risk factor for susceptibility to schizophrenia is still genetic, as shown by many family, twin, and adoption studies. The interrelationships among genetic factors, brain development, and life events with regard to the risk of schizophrenia are largely unknown. However, there are genetic conditions that seem to affect both early development and the risk of schizophrenia. For example, recent studies suggest that maternal–fetal Rh blood-group incompatibility is a risk factor for schizophrenia. The focused study of “neurodevelopmental” candidate genes in schizophrenia as a strategy for unraveling the genetics of schizophrenia is, in my opinion, of limited benefit despite the overall optimism expressed in the corresponding chapter in Neurodevelopment and Schizophrenia; current technology already allows for the simultaneous interrogation for association of all human genes.

Neurodevelopment and Schizophrenia successfully guides the reader through a large body of the latest data. Researchers in the field of biologic psychiatry and epidemiologists will benefit the most from reading it. However, the book should also appeal to medical students and general physicians, since it has implications for prevention and medical practice.

Pablo V. Gejman, M.D.
Evanston Northwestern Healthcare–Northwestern University, Chicago, IL 60201
pgejman@northwestern.edu