What can genetics tell us about the schizophrenia construct?
What can genetics tell us about the schizophrenia construct?
复制标题
关于精神分裂症的构造，遗传学能告诉我们什么？
DOI：
10.1016/j.schres.2021.12.008
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发表时间：
2022
影响因子：
4.5
通讯作者：
Smoller,JordanW
中科院分区：
文献类型：
--
作者：
Smoller,JordanW
The nosologic boundaries of schizophrenia have evolved over the past century (Kendler, 2016). While core symptoms have remained relatively consistent in descriptions of the syndrome, clinicians have recognized that many patients with features of schizophrenia do not fit neatly into the diagnostic criteria embodied in dominant classification frameworks, most notably the DSM and ICD. Establishing the validity of the schizophrenia as a diagnostic entity has been challenging in the absence of an accepted gold-standard criterion against which it could be judged. In this context, genetic epidemiology has played an important role in evaluating the validity of the construct. In addition, more recent genomic analyses offer the opportunity to evaluate validity in ways that are less subject to concerns about “reverse causality” than other biological indicators that can be consequences of illness. In this commentary, I will discuss the status of genetic studies of the schizophrenia construct and what they can or cannot tell us about its validity and utility. Well-before Robins and Guze (Robins and Guze, 1970) included familial history as a key element in their highly influential proposal for establishing the validity of psychiatric diagnoses, pedigree studies had demonstrated that schizophrenia aggregates in families. A substantial body of family-based studies in the 20th century has consistently affirmed this conclusion. Taken together, these studies find that first degree relatives of affected individuals have an approximately 10-15-fold increased risk of the disorder compared to relatives of unaffected individuals (Kendler and Gardner, 1997; Tsuang, 2000). The landmark adoption studies of Kety and colleagues (Kety et al., 1971) suggested that this familial aggregation has a genetic component.(Notably, however, the phenotypes observed in biological relatives of adoptees encompassed a range of “schizophrenia spectrum” disorders.) The heritable nature of
