Schizophrenia: A scientific graveyard or a pragmatically useful diagnostic construct?
Schizophrenia: A scientific graveyard or a pragmatically useful diagnostic construct?
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DOI：
10.1016/j.schres.2022.01.022
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发表时间：
2022-04
影响因子：
4.5
通讯作者：
Goldsmith, David R.
中科院分区：
文献类型：
--
作者：
Walker, Elaine F.;Goldsmith, David R.
精神分裂症研究作为科学“墓地”的提法最早出现在几十年前(Plum，1972)。这期特刊表明，关于精神分裂症诊断的可行性/有效性的争议仍在继续。这篇评论的前提是，这些争议是有科学原因的，它们源于这样一个事实，即大脑比其他器官更复杂，精神病学范围内的人类大脑障碍，特别是精神病，涉及的破坏几乎没有动物模型的同源。尤其是阳性精神病症状，反映了人类特有的神经基础功能障碍。最后，我们得出结论，精神分裂症的科学讨论将受益于概念清晰度的提高，但在科学进步揭示病因亚型和有效治疗之前，诊断是值得保留的。与大脑相比，作为其他医学领域(如肾脏病、心脏病学)焦点的器官系统具有更大的生物力学简单性和跨物种同源性，从而增强了动物模型(AM)的实用性。相比之下，精神病学和神经学面临着跨物种的差异，人类有独特的大脑形态、发育过程和功能能力。这对这两个领域都提出了科学挑战。干细胞衍生有机化合物的进展有可能提供见解，但也有局限性；即使在3D培养和表型图谱方面取得了进展，有机类化合物也不能概括人脑的区域特异性或发展轨迹(de Los Angeles等人，2021年；Yadav等人，2021年)。因此，非人灵长类动物(NHP)模型和有机类化合物在告知我们对复杂的人类大脑疾病的理解方面的能力都是有限的(海尔布朗纳和查菲，2019年)。
References to schizophrenia research as a scientific “graveyard” first appeared decades ago (Plum, 1972). This special issue demonstrates that controversies about the viability/validity of the diagnosis of schizophrenia have continued. The premise of this commentary is that there are scientific reasons for these controversies, and they stem from the facts that the brain is more complex than other organs and that the human brain disorders that are in psychiatry's purview, especially psychoses, involve disruptions for which there are few animal-model homologs. Positive psychotic symptoms, especially, reflect dysfunction in neural substrates that are human-specific. Finally, we conclude that scientific discussions of schizophrenia would benefit from improved conceptual clarity, but that the diagnosis is worth retaining until scientific advances reveal etiologic subtypes and effective treatments.Compared with the brain, organ systems that are the focus of other medical fields (e g., nephrology, cardiology) have greater biomechanical simplicity and cross-species homology, thereby enhancing the utility of animal models (AMs). In contrast, psychiatry and neurology are confronted by cross-species variation, with humans having a unique brain morphology, developmental course, and functional capacity. This poses scientific challenges for both fields. Advances in stem-cell–derived organoids have potential for offering insights, but there are limitations; organoids do not recapitulate the regional specificity or developmental trajectory of the human brain, even with advances in 3D-culture and phenotypic profiling (De Los Angeles et al., 2021; Yadav et al., 2021). Thus, both nonhuman primate (NHP) models and organoids are limited in their ability to inform our understanding of complex human brain disorders (Heilbronner and Chafee, 2019).
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DOI：
10.1093/cercor/bhaa365
发表时间：
2021-03-31
期刊：
Cerebral cortex (New York, N.Y. : 1991)
影响因子：
--
作者：
Changeux JP;Goulas A;Hilgetag CC
通讯作者：
Hilgetag CC
DOI：
10.1007/s00702-020-02188-w
发表时间：
2020-11
期刊：
Journal of neural transmission (Vienna, Austria : 1996)
影响因子：
--
作者：
Imamura A;Morimoto Y;Ono S;Kurotaki N;Kanegae S;Yamamoto N;Kinoshita H;Tsujita T;Okazaki Y;Ozawa H
通讯作者：
Ozawa H
影响因子：
3.4
作者：
Gregory, Michael D.;Kippenhan, J. Shane;Berman, Karen F.
通讯作者：
Berman, Karen F.
影响因子：
6.7
作者：
Tondo, L.;Vazquez, G. H.;Baldessarini, R. J.
通讯作者：
Baldessarini, R. J.
影响因子：
3.3
作者：
Holtzman CW;Trotman HD;Goulding SM;Ryan AT;Macdonald AN;Shapiro DI;Brasfield JL;Walker EF
通讯作者：
Walker EF