Genetically mediated brain abnormalities in schizophrenia

被引:23
作者
Larry J. Seidman
Heidi E. Wencel
机构
[1] Neuropsychology Laboratory, Massachusetts Mental Health Center, Boston, MA 02115
关键词
Schizophrenia; Schizophrenic Patient; Schizophrenia Patient; Brain Abnormality; Biol Psychiatry;
D O I
10.1007/s11920-003-0030-4
中图分类号
学科分类号
摘要
Schizophrenia is a highly heritable, neurobehavioral disorder; however, the mode of inheritance is complex, and linkage findings have been difficult to replicate. Some consistent linkage findings have emerged on chromosomes 1, 6, 8, 11, 13, 15, and 22. New methods are being developed for candidate gene identification, including the use of neurobiologic phenotypes observed in relatives of persons with schizophrenia. Neuroimaging studies of relatives implicate abnormal hippocampal structure and inefficient prefrontal network functioning, probably representing mild variants of the abnormalities observed in schizophrenia. These characteristics may represent stable markers of vulnerability to schizophrenia, because they are not confounded by effects of antipsychotic drugs or psychosis. Recent studies provide evidence for a small role of the catechol-O-methyltransferase gene on 22q, and the serotonin receptor transporter gene on 17q11-q12 in the development of schizophrenia. Linking genes and brain regions or networks is an important step in identification of the pathophysiology of schizophrenia. Copyright © 2003 by Current Science Inc.
引用
收藏
页码:135 / 144
页数:9
相关论文
共 103 条
[41]  
Manoach D.S., Gollub R.L., Benson E.S., Et al., Schizophrenic subjects show aberrant fMRI activation of dorsolateral prefrontal cortex and basal ganglia during working memory performance, Biol. Psychiatry, 48, pp. 99-109, (2000)
[42]  
Curtis V.A., Bullmore E.T., Morris R.G., Et al., Attenuated frontal activation in schizophrenia may be task dependent, Schizophr. Res., 37, pp. 35-44, (1999)
[43]  
Callicott J.H., Bertolino A., Mattay V.S., Et al., Physiological dysfunction of the dorsolateral prefrontal cortex in schizophrenia revisited, Cerebral Cortex, 10, pp. 1078-1092, (2000)
[44]  
Ramsey N.F., Konig H.A., Welles P., Et al., Excessive recruitment of neural systems subserving logical reasoning in schizophrenia, Brain, 125, pp. 1793-1807, (2002)
[45]  
Selemon L.D., Rajkowska G., Goldman-Rakic P.S., Abnormally high neuronal density in the schizophrenic cortex: A morphometric analysis of prefrontal area 9 and area 17, Arch. Gen. Psychiatry, 52, pp. 805-818, (1995)
[46]  
Selemon L.D., Goldman-Rakic P.S., The reduced neuropil hypothesis: A circuit based model of schizophrenia, Biol. Psychiatry, 45, pp. 17-25, (1999)
[47]  
Lawrie S.M., Buechel C., Whalley H., Et al., Reduced frontotemporal functional connectivity in schizophrenia associated with auditory hallucinations, Biol. Psychiatry, 51, pp. 1008-1011, (2002)
[48]  
Bullmore E.T., Frangou S., Murray R.M., The dysplastic net hypothesis: An integration of developmental and dysconnectivity theories of schizophrenia, Schizophr. Res., 28, pp. 143-156, (1997)
[49]  
Weinberger D.R., Berman K.F., Suddath R., Torrey E.F., Evidence of dysfunction of a prefrontal-limbic network in schizophrenia: A magnetic resonance imaging and region cerebral blood flow study of discordant monozygotic twins, Am. J. Psychiatry, 149, pp. 890-897, (1992)
[50]  
Staal W.G., Hulshoff H.E., Schnack H., Et al., Partial volume decrease of the thalamus in relatives of patients with schizophrenia, Am. J. Psychiatry, 155, pp. 1784-1786, (1998)