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精神分裂症:遗传学视角(综述)

Schizophrenia: a genetic perspective (review).

作者信息

Shastry Barkur S

机构信息

Department of Biological Sciences, Oakland University, Rochester, MI 48309, USA.

出版信息

Int J Mol Med. 2002 Mar;9(3):207-12.

Abstract

Schizophrenia is a complex neurodevelopmental disorder characterized by mental dysfunction across multiple domains of the brain. It affects 1% of world's general population and the nature of neurobiological lesions in the schizophrenic brain are not known. Although the exact etiology of the disorder is not understood, twin, family and adoption studies have provided consistent evidence that genetic factors play a major role in the pathogenesis. A genome-wide genetic linkage screen identified loci on chromosomes 1, 2, 4, 5, 6, 7, 8, 9, 10, 11, 13, 15, 18, 22 and the X with positive lod scores, thus excluding a single major locus for schizophrenia. Association studies have generated disappointing results in identifying the susceptible DNA sequence variants and the anticipation hypothesis on trinucleotide repeat expansion provided equivocal results or lack of enthusiasm. Although there are no biological markers at present, the recent finding that human endogenous retrovirus is activated in cerebrospinal fluid as well as in the postmortem schizophrenic brain may change our understanding of the etiopathogenesis of this disease. Meanwhile, treatment with newly developed anti-psychotic drugs combined with educational and cognitive rehabilitation procedure may help the patients to cope with the illness.

摘要

精神分裂症是一种复杂的神经发育障碍,其特征是大脑多个领域出现精神功能障碍。它影响着世界1%的普通人群,而精神分裂症患者大脑中神经生物学损伤的本质尚不清楚。尽管这种疾病的确切病因尚不清楚,但双胞胎、家族和收养研究提供了一致的证据,表明遗传因素在发病机制中起主要作用。一项全基因组遗传连锁筛查确定了1号、2号、4号、5号、6号、7号、8号、9号、10号、11号、13号、15号、18号、22号染色体以及X染色体上具有阳性lod分数的基因座,从而排除了精神分裂症的单一主要基因座。关联研究在识别易感DNA序列变异方面产生了令人失望的结果,关于三核苷酸重复扩增的预期假说也得出了模棱两可的结果或缺乏可信度。尽管目前尚无生物学标志物,但最近发现人类内源性逆转录病毒在脑脊液以及死后的精神分裂症患者大脑中被激活,这可能会改变我们对这种疾病病因发病机制的理解。与此同时,使用新开发的抗精神病药物结合教育和认知康复程序进行治疗,可能有助于患者应对疾病。

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