Schmidt-Kastner Rainald, van Os Jim, W M Steinbusch Harry, Schmitz Christoph
Department of Psychiatry and Neuropsychology, Division of Cellular Neuroscience, Maastricht University, 6200 MD Maastricht, The Netherlands.
Schizophr Res. 2006 Jun;84(2-3):253-71. doi: 10.1016/j.schres.2006.02.022. Epub 2006 Apr 24.
Neurodevelopmental changes may underlie the brain dysfunction seen in schizophrenia. While advances have been made in our understanding of the genetics of schizophrenia, little is known about how non-genetic factors interact with genes for schizophrenia. The present analysis of genes potentially associated with schizophrenia is based on the observation that hypoxia prevails in the embryonic and fetal brain, and that interactions between neuronal genes, molecular regulators of hypoxia, such as hypoxia-inducible factor 1 (HIF-1), and intrinsic hypoxia occur in the developing brain and may create the conditions for complex changes in neurodevelopment. Consequently, we searched the literature for currently hypothesized candidate genes for susceptibility to schizophrenia that may be subject to ischemia-hypoxia regulation and/or associated with vascular expression. Genes were considered when at least two independent reports of a significant association with schizophrenia had appeared in the literature. The analysis showed that more than 50% of these genes, particularly AKT1, BDNF, CAPON, CCKAR, CHRNA7, CNR1, COMT, DNTBP1, GAD1, GRM3, IL10, MLC1, NOTCH4, NRG1, NR4A2/NURR1, PRODH, RELN, RGS4, RTN4/NOGO and TNF, are subject to regulation by hypoxia and/or are expressed in the vasculature. Future studies of genes proposed as candidates for susceptibility to schizophrenia should include their possible regulation by physiological or pathological hypoxia during development as well as their potential role in cerebral vascular function.
神经发育变化可能是精神分裂症中所见大脑功能障碍的潜在原因。虽然我们对精神分裂症遗传学的理解取得了进展，但对于非遗传因素如何与精神分裂症相关基因相互作用却知之甚少。目前对可能与精神分裂症相关的基因的分析基于以下观察结果：缺氧在胚胎和胎儿大脑中普遍存在，并且神经元基因、缺氧分子调节因子（如缺氧诱导因子1，HIF - 1）之间的相互作用以及内在缺氧在发育中的大脑中发生，这可能为神经发育的复杂变化创造条件。因此，我们在文献中搜索目前假设的精神分裂症易感性候选基因，这些基因可能受缺血缺氧调节和/或与血管表达相关。当文献中至少出现两篇关于与精神分裂症有显著关联的独立报告时，这些基因才会被考虑。分析表明，这些基因中超过50%，特别是AKT1、BDNF、CAPON、CCKAR、CHRNA7、CNR1、COMT、DNTBP1、GAD1、GRM3、IL10、MLC1、NOTCH4、NRG1、NR4A2/NURR1、PRODH、RELN、RGS4、RTN4/NOGO和TNF，受缺氧调节和/或在血管系统中表达。未来对被提议作为精神分裂症易感性候选基因的研究应包括它们在发育过程中可能受到的生理或病理缺氧调节以及它们在脑血管功能中的潜在作用。
