Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences.
Shimonoseki Hospital.
Int J Neuropsychopharmacol. 2021 May 18;24(5):367-382. doi: 10.1093/ijnp/pyaa097.
The mortality rate of patients with schizophrenia is high, and life expectancy is shorter by 10 to 20 years. Metabolic abnormalities including type 2 diabetes mellitus (T2DM) are among the main reasons. The prevalence of T2DM in patients with schizophrenia may be epidemiologically frequent because antipsychotics induce weight gain as a side effect and the cognitive dysfunction of patients with schizophrenia relates to a disordered lifestyle, poor diet, and low socioeconomic status. Apart from these common risk factors and risk factors unique to schizophrenia, accumulating evidence suggests the existence of common susceptibility genes between schizophrenia and T2DM. Functional proteins translated from common genetic susceptibility genes are known to regulate neuronal development in the brain and insulin in the pancreas through several common cascades. In this review, we discuss common susceptibility genes, functional cascades, and the relationship between schizophrenia and T2DM. Many genetic and epidemiological studies have reliably associated the comorbidity of schizophrenia and T2DM, and it is probably safe to think that common cascades and mechanisms suspected from common genes' functions are related to the onset of both schizophrenia and T2DM. On the other hand, even when genetic analyses are performed on a relatively large number of comorbid patients, the results are sometimes inconsistent, and susceptibility genes may carry only a low or moderate risk. We anticipate future directions in this field.
精神分裂症患者的死亡率较高，预期寿命缩短 10 到 20 年。包括 2 型糖尿病（T2DM）在内的代谢异常是主要原因之一。由于抗精神病药物会导致体重增加，而精神分裂症患者的认知功能障碍与生活方式紊乱、饮食不良和低社会经济地位有关，因此精神分裂症患者中 T2DM 的患病率可能在流行病学上较为频繁。除了这些常见的风险因素和精神分裂症特有的风险因素外，越来越多的证据表明精神分裂症和 T2DM 之间存在共同的易感基因。从常见遗传易感基因翻译而来的功能蛋白通过几个共同的级联反应，已知可调节大脑中的神经元发育和胰腺中的胰岛素。在这篇综述中，我们讨论了常见的易感基因、功能级联反应以及精神分裂症和 T2DM 之间的关系。许多遗传和流行病学研究可靠地将精神分裂症和 T2DM 的共病联系起来，因此可以认为，从共同基因功能推断出的共同级联和机制可能与精神分裂症和 T2DM 的发病有关。另一方面，即使对大量共病患者进行基因分析，结果有时也不一致，易感基因可能只携带低风险或中风险。我们期待该领域的未来发展方向。
