Neurodevelopment and Schizophrenia
http://www.100md.com
《新英格兰医药杂志》
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(Edited by Matcheri Keshav)
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(Edited by Matcheri Keshav)