Dopamine-prolactin pathway potentially contributes to the schizophrenia and type 2 diabetes comorbidity.
Dopamine-prolactin pathway potentially contributes to the schizophrenia and type 2 diabetes comorbidity.
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DOI：
10.1038/tp.2016.50
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发表时间：
2016-04-19
影响因子：
6.8
通讯作者：
Postolache TT
中科院分区：
文献类型：
--
作者：
Gragnoli C;Reeves GM;Reazer J;Postolache TT
精神分裂症（SCZ）和2型糖尿病（T2D）在临床上是相关的，常识将这种关联归因于抗精神病药物治疗的副作用。然而，即使是未用药的SCZ患者发生T2D的风险也会增加。多巴胺功能障碍在SCZ中起核心作用。众所周知，多巴胺通过多巴胺受体2 （DR2D）组成性地抑制泌乳素（PRL）的分泌。如果多巴胺增加或多巴胺受体功能亢进，PRL可能会降低。在第一次SCZ发作时，低PRL水平与更严重的症状相关。PRL在人类和社会关系中是必不可少的，它与葡萄糖稳态有关。多巴胺功能障碍，除了有助于SCZ症状外，还可能导致食欲改变和T2D。据我们所知，目前还没有关于SCZ-T2D合并症的遗传学研究共同关注多巴胺和PRL通路，试图捕捉与可能的疾病表现异质性相关的分子异质性。在这篇以多巴胺- PRL通路为中心的假设驱动的关于SCZ与T2D关联的综述中，我们报告了对PRL和多巴胺的已知知识的具体修订，我们认为这是两种疾病之间缺失的联系之一。我们认为有必要开展新的研究，以确定PRL和多巴胺途径在SCZ-T2D合并症中的遗传作用。
Schizophrenia (SCZ) and type 2 diabetes (T2D) are clinically associated, and common knowledge attributes this association to side effects of antipsychotic treatment. However, even drug-naive patients with SCZ are at increased risk for T2D. Dopamine dysfunction has a central role in SCZ. It is well-known that dopamine constitutively inhibits prolactin (PRL) secretion via the dopamine receptor 2 (DR2D). If dopamine is increased or if dopamine receptors hyperfunction, PRL may be reduced. During the first SCZ episode, low PRL levels are associated with worse symptoms. PRL is essential in human and social bonding, as well as it is implicated in glucose homeostasis. Dopamine dysfunction, beyond contributing to SCZ symptoms, may lead to altered appetite and T2D. To our knowledge, there are no studies of the genetics of the SCZ–T2D comorbidity focusing jointly on the dopamine and PRL pathway in the attempt to capture molecular heterogeneity correlated to possible disease manifestation heterogeneity. In this dopamine–PRL pathway-focused-hypothesis-driven review on the association of SCZ with T2D, we report a specific revision of what it is known about PRL and dopamine in relation to what we theorize is one of the missing links between the two disorders. We suggest that new studies are necessary to establish the genetic role of PRL and dopamine pathway in SCZ–T2D comorbidity.