Owen Michael J
Centre for Neuropsychiatric Genetics and Genomics, Neuroscience and Mental Health Innovation Institute and Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff CF10 3AT, UK.
R Soc Open Sci. 2023 Feb 22;10(2):230125. doi: 10.1098/rsos.230125. eCollection 2023 Feb.
Schizophrenia is a common, complex, heterogeneous psychiatric syndrome which can have profound impacts on affected individuals and imposes significant burdens on society. Despite intensive research, it has been challenging to understand basic mechanisms and to identify novel therapeutic targets. Given its high heritability and the complexity and inaccessibility of the human brain, much hope has been invested in the application of genomics as a route to better understanding. This work has identified many common and rare risk alleles and laid the foundations for a new generation of mechanistic studies. Genomics has also thrown new light on the relationship between schizophrenia and other psychiatric disorders and revealed its previously unappreciated aetiological relationship with childhood neurodevelopmental disorders, providing further evidence that it has its origins in disturbances of brain development. In addition, genomic findings suggest that the condition reflects fundamental disturbances in neuronal, and particularly synaptic, function that impact broadly on brain function, rather than being a disorder of specific brain regions and circuits. Finally, genomics has provided a plausible solution to the evolutionary paradox of how the condition persists in the face of high heritability and reduced fecundity.
精神分裂症是一种常见、复杂且异质性的精神综合征,会对患者个体产生深远影响,并给社会带来重大负担。尽管进行了深入研究,但理解其基本机制和确定新的治疗靶点仍具有挑战性。鉴于其高遗传性以及人类大脑的复杂性和难以接近性,人们寄希望于通过基因组学的应用来更好地理解该疾病。这项工作已经确定了许多常见和罕见的风险等位基因,并为新一代的机制研究奠定了基础。基因组学还为精神分裂症与其他精神障碍之间的关系提供了新的见解,并揭示了其与儿童神经发育障碍此前未被认识到的病因关系,进一步证明了它起源于大脑发育紊乱。此外,基因组学研究结果表明,这种疾病反映了神经元,尤其是突触功能的基本紊乱,广泛影响大脑功能,而不是特定脑区和神经回路的疾病。最后,基因组学为该疾病在高遗传性和生育力降低的情况下如何持续存在这一进化悖论提供了一个合理的解决方案。