Tsuang M T, Faraone S V
Harvard Medical School, Department of Psychiatry, Massachusetts Mental Health Center, Boston 02115, USA.
Schizophr Res. 1995 Oct;17(2):161-75. doi: 10.1016/0920-9964(95)00057-s.
To confirm etiological heterogeneity, it is required that schizophrenic patients may be separated into at least two classes having different known etiologies and, perhaps, different pathophysiological signatures. In contrast, the homogeneity hypothesis asserts that there is a single necessary and sufficient cause or configuration of causes of schizophrenia. Because the link between phenotypic heterogeneity and etiological heterogeneity is tenuous, attempts to use purely phenotypic data to infer etiologic heterogeneity must be viewed cautiously. We examined three candidate causes for schizophrenia: genes, obstetric complications and viral infection. Cytogenetic studies show that some rare cases of schizophrenia are due to gross abnormalities of chromosomes. As for the large majority of schizophrenic patients, the candidate cause data most certainly reject the most parsimonious version of the hypothesis of etiological homogeneity: that all schizophrenia is caused by exactly the same pattern of genetic mutations, birth related complications and exposure to the same viral infections. We conclude that the heterogeneity debate should consider the possibility of rewording the question: 'Heterogeneity: yes or no?' to 'Heterogeneity: how much?'
为了证实病因异质性，要求精神分裂症患者至少可被分为具有不同已知病因且可能具有不同病理生理特征的两类。相比之下，同质性假说认为，精神分裂症存在单一的必要且充分病因或病因组合。由于表型异质性与病因异质性之间的联系并不紧密，因此必须谨慎看待试图使用纯表型数据来推断病因异质性的做法。我们研究了精神分裂症的三种候选病因：基因、产科并发症和病毒感染。细胞遗传学研究表明，一些罕见的精神分裂症病例是由染色体的明显异常所致。至于绝大多数精神分裂症患者，候选病因数据无疑否定了病因同质性假说的最简约版本：即所有精神分裂症都是由完全相同模式的基因突变、与出生相关的并发症以及接触相同病毒感染所引起的。我们得出结论，关于异质性的争论应考虑重新表述问题的可能性：从“异质性：是或否？”改为“异质性：程度如何？”
