Department of Neurology, Eginition University Hospital, National and Kapodistrian University of Athens, 11528 Athens, Greece.
Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 M. Asias Street, 11527 Athens, Greece.
Medicina (Kaunas). 2023 Jun 13;59(6):1138. doi: 10.3390/medicina59061138.
: Parkinson's disease (PD) is a clinically heterogeneous disorder with poorly understood pathological contributing factors. Depression presents one of the most frequent non-motor PD manifestations, and several genetic polymorphisms have been suggested that could affect the depression risk in PD. Therefore, in this review we have collected recent studies addressing the role of genetic factors in the development of depression in PD, aiming to gain insights into its molecular pathobiology and enable the future development of targeted and effective treatment strategies. : we have searched PubMed and Scopus databases for peer-reviewed research articles published in English (pre-clinical and clinical studies as well as relevant reviews and meta-analyses) investigating the genetic architecture and pathophysiology of PD depression. : in particular, polymorphisms in genes related to the serotoninergic pathway (sodium-dependent serotonin transporter gene, , tryptophan hydrolase-2 gene, ), dopamine metabolism and neurotransmission (dopamine receptor D3 gene, , aldehyde dehydrogenase 2 gene, , neurotrophic factors (brain-derived neurotrophic factor gene, ), endocannabinoid system (cannabinoid receptor gene, CNR1), circadian rhythm (thyrotroph embryonic factor gene, ), the sodium-dependent neutral amino acid transporter B(0)AT2 gene, ), and genetic locus were detected as altering susceptibility to depression among PD patients. However, polymorphisms in the dopamine transporter gene (), monoamine oxidase A () and B () genes, catechol-O-methyltransferase gene (), , and have not been related to PD depression. : the specific mechanisms underlying the potential role of genetic diversity in PD depression are still under investigation, however, there is evidence that they may involve neurotransmitter imbalance, mitochondrial impairment, oxidative stress, and neuroinflammation, as well as the dysregulation of neurotrophic factors and their downstream signaling pathways.
帕金森病（PD）是一种临床表现异质性差且发病机制尚不完全清楚的疾病。抑郁是 PD 最常见的非运动症状之一，有几种遗传多态性被认为可能影响 PD 患者的抑郁风险。因此，在本综述中，我们收集了最近的研究，探讨了遗传因素在 PD 抑郁发生中的作用，旨在深入了解其分子病理生物学，并为未来开发有针对性和有效的治疗策略提供依据。
我们在 PubMed 和 Scopus 数据库中搜索了以英文发表的同行评议研究文章（临床前和临床研究以及相关综述和荟萃分析），这些文章探讨了 PD 抑郁的遗传结构和病理生理学。
特别是，与 5-羟色胺能途径（钠依赖性 5-羟色胺转运体基因、色氨酸羟化酶-2 基因）、多巴胺代谢和神经传递（多巴胺受体 D3 基因、多巴胺受体 D2 基因、儿茶酚-O-甲基转移酶基因）、神经营养因子（脑源性神经营养因子基因）、内源性大麻素系统（大麻素受体基因 CNR1）、生物钟（甲状腺激素胚胎因子基因）、钠依赖性中性氨基酸转运体 B(0)AT2 基因）和 遗传位点的多态性被检测为改变 PD 患者对抑郁的易感性。然而，多巴胺转运体基因（）、单胺氧化酶 A（）和 B（）基因、儿茶酚-O-甲基转移酶基因（）、和 多态性与 PD 抑郁无关。
遗传多样性在 PD 抑郁中的潜在作用的具体机制仍在研究中，但有证据表明，它们可能涉及神经递质失衡、线粒体损伤、氧化应激和神经炎症，以及神经营养因子及其下游信号通路的失调。
