Division of Molecular and Clinical Neurobiology, Department of Psychiatry, Ludwig-Maximilians-University, Nußbaumstr. 7, 80336 Munich, Germany.
Prog Neuropsychopharmacol Biol Psychiatry. 2010 Dec 1;34(8):1375-80. doi: 10.1016/j.pnpbp.2010.06.018. Epub 2010 Jul 1.
There is a relatively high genetic heritability of schizophrenia as shown by family, twin and adoption studies. A large number of hypotheses on the causes of schizophrenia occurred over time. In this review we focus on genetic findings related to potential alterations of intracellular Ca-homeostasis in association with schizophrenia. First, we provide evidence for the NMDA/glutamatergic theory of schizophrenia including calcium processes. We mainly focus on genes including: DAO (D-amino acid oxidase), DAOA (D-amino acid oxidase activator), DTNBP1 (Dysbindin 1, dystrobrevin-binding protein 1), NRG1 (Neuregulin 1), ERBB4 (v-erb-a erythroblastic leukemia viral oncogene homolog 4, avian), NOS1 (nitric oxide synthase 1, neuronal) and NRGN (Neurogranin). Furthermore, a gene coding for a calcium channel subunit (CACNA1C: calcium channel, voltage-dependent, L type, alpha 1C subunit) is discussed in the light of schizophrenia whereas genetic findings related to alterations in the intracellular Ca-homeostasis associated specifically with dopaminergic and serotonergic neurotransmission in schizophrenia are not herein closer reviewed. Taken together there is converging evidence for the contribution of genes potentially related to alterations in intracellular Ca-homeostasis to the risk of schizophrenia. Replications and functional studies will hopefully provide further insight into these genetic variants and the underlying processes.
精神分裂症存在相对较高的遗传易感性，这一点已被家族、双胞胎和收养研究证明。随着时间的推移，出现了大量关于精神分裂症病因的假说。在这篇综述中，我们重点关注与精神分裂症相关的细胞内钙稳态潜在改变有关的遗传发现。首先，我们提供了 NMDA/谷氨酸能理论的证据，包括钙过程与精神分裂症有关。我们主要关注包括以下基因的证据：DAO（D-氨基酸氧化酶）、DAOA（D-氨基酸氧化酶激活剂）、DTNBP1（Dysbindin 1，dystrobrevin 结合蛋白 1）、NRG1（Neuregulin 1）、ERBB4（v-erb-a 红细胞白血病病毒致癌基因同源物 4，禽类）、NOS1（一氧化氮合酶 1，神经元）和 NRGN（Neurogranin）。此外，还讨论了与精神分裂症相关的钙通道亚基（CACNA1C：电压依赖性钙通道，L 型，α 1C 亚基）编码基因，而与多巴胺能和血清素能神经递质传递中细胞内钙稳态改变相关的遗传发现则不在此更详细地综述。总之，有越来越多的证据表明，潜在与细胞内钙稳态改变有关的基因可能与精神分裂症的风险有关。复制和功能研究有望为这些遗传变异和潜在过程提供进一步的了解。
