Zivanović O, Borisev L
Klinika za psihijatriju, Institut za neurologiju, psihijatriju i mentalno zdravlje, Medicinski fakultet, Novi Sad.
Med Pregl. 1999 Jan-Feb;52(1-2):25-8.
The importance of inheritance in the development of schizophrenia was recorded in classic papers by Kraepelin and Bleuler. These observations have been confirmed by the contemporary research. In this paper, we summarize the results of genetic-epidemiological studies that include family, twin and adoption studies, as well as the results of segregation analysis and molecular-genetic research. Family studies indicate increased morbidity risk in the relatives of patients with schizophrenia, that augments with the degree of relation. Twin studies also suggest the importance of genetic factors demonstrating higher rates of concordance for the disorder in monozygotic (MZ) than in dizygotic (DZ) twins and consistent MZ/DZ ratios across the studies. Adoption studies provide further evidence for genetic vulnerability, showing an association between biological relatives separated at birth. The concept of "schizophrenia spectrum" is based on the observation of the familial aggregation of several hierarchically defined disorders in relatives of schizophrenic probands. Schizophrenia, schizoaffective disorder, schizotypal and paranoid personality disorder, other nonaffective psychoses and psychotic affective disease, according to this concept, represent manifestations of varying severity, of the same underlying vulnerability, which is transmitted within families. The results of segregation analyses support rather polygenic than monogenic inheritance, if schizophrenia is genetically homogeneous. However, the possibility of genetic heterogeneity augments the interest for searching for vulnerability genes with linkage. The results of linkage studies, indicating association between schizophrenia and markers on chromosomes 5, 6, 8 and 22, have not yet been replicated on independent samples of probands. Recent findings indicate that schizophrenia may be caused by unstable DNA (the expansion of trinucleotide repeated sequences at the disease locus). This could explain the departure from Mendelian inheritance, highly variable phenotype and wide ranging age of onset in schizophrenia. Further research in this field could not only clarify the mode of the transmission of the liability for schizophrenia and the relationship of genetic and environmental factors in the development of the disorder, but also determine which characteristics, behavior and physiological variables schizophrenia genes code for. This would, in addition, contribute to our understanding of the biological basis of schizophrenia.
精神分裂症发展过程中遗传因素的重要性在克雷佩林和布鲁勒的经典论文中已有记载。这些观察结果已得到当代研究的证实。在本文中，我们总结了遗传流行病学研究的结果，包括家族研究、双生子研究和收养研究，以及分离分析和分子遗传学研究的结果。家族研究表明，精神分裂症患者亲属的发病风险增加，且这种风险随着亲属关系的亲疏程度而增加。双生子研究也表明了遗传因素的重要性，显示同卵双胞胎（MZ）患该疾病的一致率高于异卵双胞胎（DZ），且各项研究中的MZ/DZ比率一致。收养研究为遗传易感性提供了进一步证据，表明出生时即分离的生物学亲属之间存在关联。“精神分裂症谱系”的概念基于对精神分裂症先证者亲属中几种分层定义的疾病家族聚集现象的观察。根据这一概念，精神分裂症、分裂情感性障碍、分裂型和偏执型人格障碍、其他非情感性精神病和精神病性情感疾病代表了同一潜在易感性的不同严重程度表现，这种易感性在家族中传递。如果精神分裂症在遗传上是同质的，分离分析的结果支持多基因而非单基因遗传。然而，遗传异质性的可能性增加了通过连锁分析寻找易感性基因的兴趣。连锁研究结果表明精神分裂症与5号、6号、8号和22号染色体上的标记物有关联，但尚未在独立的先证者样本中得到重复验证。最近的研究发现表明，精神分裂症可能由不稳定的DNA（疾病位点处三核苷酸重复序列的扩增）引起。这可以解释精神分裂症为何偏离孟德尔遗传、具有高度可变的表型以及广泛的发病年龄范围。该领域的进一步研究不仅可以阐明精神分裂症易感性的传递方式以及该疾病发展过程中遗传和环境因素的关系，还可以确定精神分裂症基因编码哪些特征、行为和生理变量。此外，这将有助于我们理解精神分裂症的生物学基础。
