Schizophrenia (SCZ) and major depressive disorder (MDD) in treatment-naive patients are associated with increased risk for type 2 diabetes (T2D) and metabolic syndrome (MetS). SCZ, MDD, T2D, and MetS are often comorbid and their comorbidity increases cardiovascular risk: Some risk genes are likely co-shared by them. For instance, transcription factor 7-like 2 (TCF7L2) and proteasome 26S subunit, non-ATPase 9 (PSMD9) are two genes independently reported as contributing to T2D and SCZ, and PSMD9 to MDD as well. However, there are scarce data on the shared genetic risk among SCZ, MDD, T2D, and/or MetS. Here, we briefly describe T2D, MetS, SCZ, and MDD and their genetic architecture. Next, we report separately about the comorbidity of SCZ and MDD with T2D and MetS, and their respective genetic overlap. We propose a novel hypothesis that genes of the prolactin (PRL)-pathway may be implicated in the comorbidity of these disorders. The inherited predisposition of patients with SCZ and MDD to psychoneuroendocrine dysfunction may confer increased risk of T2D and MetS. We illustrate a strategy to identify risk variants in each disorder and in their comorbid psychoneuroendocrine and mental-metabolic dysfunctions, advocating for studies of genetically homogeneous and phenotype-rich families. The results will guide future studies of the shared predisposition and molecular genetics of new homogeneous endophenotypes of SCZ, MDD, and metabolic impairment.

中文翻译：

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共同的遗传学和可能的风险基因途径部分解释了精神分裂症，重度抑郁症，2型糖尿病和代谢综合征的合并症。

初治患者的精神分裂症（SCZ）和重度抑郁症（MDD）与2型糖尿病（T2D）和代谢综合征（MetS）的风险增加相关。SCZ，MDD，T2D和MetS通常是合并症，它们的合并症会增加心血管疾病的风险：某些风险基因可能与他们共同共享。例如，转录因子7样2（TCF7L2）和蛋白酶体26S亚基，非ATPase 9（PSMD9）是两个独立报告为T2D和SCZ以及PSMD9对MDD起作用的基因。但是，关于SCZ，MDD，T2D和/或MetS之间共同的遗传风险的数据很少。在这里，我们简要介绍T2D，MetS，SCZ和MDD及其遗传结构。接下来，我们分别报告SCZ和MDD与T2D和MetS的合并症，以及它们各自的遗传重叠。我们提出了一个新的假设，即催乳素（PRL）途径的基因可能与这些疾病的合并症有关。SCZ和MDD患者遗传性易患神经神经内分泌功能障碍可能会增加T2D和MetS的风险。我们举例说明了一种策略，用于识别每种疾病及其合并的神经神经内分泌和精神代谢功能异常的风险变异，提倡对遗传同质和表型丰富的家庭进行研究。该结果将指导未来对SCZ，MDD和代谢功能障碍的新同质内表型的共同易感性和分子遗传学的研究。SCZ和MDD患者遗传性易患神经神经内分泌功能障碍可能会增加T2D和MetS的风险。我们举例说明了一种策略，用于识别每种疾病及其合并的神经神经内分泌和精神代谢功能异常的风险变异，提倡对遗传同质和表型丰富的家庭进行研究。该结果将指导未来对SCZ，MDD和代谢功能障碍的新同质内表型的共同易感性和分子遗传学的研究。SCZ和MDD患者遗传性易患神经神经内分泌功能障碍可能会增加T2D和MetS的风险。我们举例说明了一种策略，用于识别每种疾病及其合并的神经神经内分泌和精神代谢功能异常的风险变异，提倡对遗传同质和表型丰富的家庭进行研究。该结果将指导未来对SCZ，MDD和代谢功能障碍的新同质内表型的共同易感性和分子遗传学的研究。