Crow T J
Br J Psychiatry. 1984 Sep;145:243-53. doi: 10.1192/bjp.145.3.243.
The extent to which concordance rates for schizophrenia in monozygotic twins (between 36 and 58%) fall short of 100% is often taken as an index of the role of an environmental factor in schizophrenia, but such an agent remains elusive. That schizophrenic symptoms are observed in some viral illnesses suggests that schizophrenia might be due to a gene-virus interaction, but analysis of age of onset in pairs of siblings with the disease rules out horizontal transmission. An alternative hypothesis is proposed that onset of disease is due to the expression of a 'provirus', which is integrated in the genome, having been acquired either by prenatal infection or in the germ-line from an affected parent; this could explain why the season of birth effect is accentuated in, and perhaps confined to the group of patients without a family history of the disease. Germ-line integration is known to occur following infection with agents of the retrovirus class. Such agents can integrate at many sites in the host genome, but their interactions with proto-oncogenes (cellular genes which may act as growth factors) identify one type of integration site, and are associated with some of their pathogenic effects. Some characteristics of schizophrenic illness, particularly their selectivity for the dominant hemisphere, can be understood on the assumption that the virus (perhaps a retrovirus) responsible for the disease interacts with a proto-oncogene, which induces the asymmetrical brain growth responsible for laterality and cerebral dominance. The aetiologies of manic-depressive illness and schizophrenia may be related (the season of birth and onset effects are the same for the two conditions) and there is some evidence that the former transmutes into the latter in succeeding generations. The persistence of the functional psychoses may be due to the ability of the psychosis gene (or 'provirus') to induce change in the genetic mechanisms responsible for the development of laterality.
同卵双胞胎中精神分裂症的一致率（在36%至58%之间）未达到100%，这一情况常被视为环境因素在精神分裂症中作用的一个指标，但这样一种因素仍难以捉摸。在一些病毒性疾病中观察到精神分裂症症状，这表明精神分裂症可能是由于基因 - 病毒相互作用，但对患此病的同胞对发病年龄的分析排除了水平传播。提出了另一种假说，即疾病的发作是由于一种“前病毒”的表达，这种前病毒整合在基因组中，它要么是通过产前感染获得，要么是从患病父母的生殖系中获得；这可以解释为什么出生季节效应在没有家族病史的患者群体中更为明显，甚至可能仅限于该群体。已知在感染逆转录病毒类病原体后会发生生殖系整合。这类病原体可以整合到宿主基因组的许多位点，但它们与原癌基因（可能充当生长因子的细胞基因）的相互作用确定了一种整合位点类型，并与它们的一些致病作用相关。假设导致该疾病的病毒（可能是一种逆转录病毒）与一个原癌基因相互作用，诱导负责偏侧性和大脑优势的不对称大脑生长，那么就可以理解精神分裂症疾病的一些特征，特别是它们对优势半球的选择性。躁狂抑郁症和精神分裂症的病因可能相关（两种病症的出生季节和发病效应相同），并且有一些证据表明前者在后代中会转变为后者。功能性精神病的持续存在可能是由于精神病基因（或“前病毒”）能够诱导负责偏侧性发展的遗传机制发生变化。
