Schizophrenia as a disorder of neurodevelopment

被引:821
作者
Lewis, DA [1 ]
Levitt, P
机构
[1] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA
[2] Univ Pittsburgh, Sch Med, Dept Neurosci, Pittsburgh, PA 15213 USA
[3] Univ Pittsburgh, Sch Med, Dept Neurobiol, Pittsburgh, PA 15213 USA
[4] Vanderbilt Univ, JF Kennedy Ctr Human Dev, Nashville, TN 37203 USA
关键词
neuropsychiatric disorder; genetics; environment; psychosis; polygenic;
D O I
10.1146/annurev.neuro.25.112701.142754
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
A combination of genetic susceptibility and environmental perturbations appear to be necessary for the expression of schizophrenia. In addition, the pathogenesis of the disease is hypothesized to be neurodevelopmental in nature based on reports of an excess of adverse events during the pre- and perinatal periods, the presence of cognitive and behavioral signs during childhood and adolescence, and the lack of evidence of a neurodegenerative process in most individuals with schizophrenia. Recent studies of neurodevelopmental mechanisms strongly suggest that no single gene or factor is responsible for driving a highly complex biological process. Together, these findings suggest that combinatorial genetic and environmental factors, which disturb a normal developmental course early in life, result in molecular and histogenic responses that cumulatively lead to different developmental trajectories and the clinical phenotype recognized as schizophrenia.
引用
收藏
页码:409 / 432
页数:24
相关论文
共 119 条
[91]   Reelin is a serine protease of the extracellular matrix [J].
Quattrocchi, CC ;
Wannenes, F ;
Persico, AM ;
Ciafré, SA ;
D'Arcangelo, G ;
Farace, MG ;
Keller, F .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (01) :303-309
[92]   CONCURRENT OVERPRODUCTION OF SYNAPSES IN DIVERSE REGIONS OF THE PRIMATE CEREBRAL-CORTEX [J].
RAKIC, P ;
BOURGEOIS, JP ;
ECKENHOFF, MF ;
ZECEVIC, N ;
GOLDMANRAKIC, PS .
SCIENCE, 1986, 232 (4747) :232-235
[93]  
Rakic P, 2000, RES PRO CEL, V30, P1
[94]  
REIK W, 1993, DEVELOPMENT, V119, P933
[95]  
RISCH N, 1984, AM J HUM GENET, V36, P1039
[96]   Searching for genetic determinants in the new millennium [J].
Risch, NJ .
NATURE, 2000, 405 (6788) :847-856
[97]  
Roberts G., 2000, NEUROPATHOLOGY SCHIZ, P137
[98]   Minor physical anomalies and schizophrenia spectrum disorders: A prospective investigation [J].
Schiffman, J ;
Ekstrom, M ;
LaBrie, J ;
Schulsinger, F ;
Sorensen, H ;
Mednick, S .
AMERICAN JOURNAL OF PSYCHIATRY, 2002, 159 (02) :238-243
[99]   Epigenetic and genotype-specific effects on the stability of de Novo imposed methylation patterns in transgenic mice [J].
Schumacher, A ;
Koetsier, PA ;
Hertz, J ;
Doerfler, W .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (48) :37915-37921
[100]   Prenatal exposure to influenza and schizophrenia in Surinamese and Dutch Antillean immigrants to The Netherlands [J].
Selten, JP ;
Slaets, J ;
Kahn, R .
SCHIZOPHRENIA RESEARCH, 1998, 30 (01) :101-103