Department of Neurology, China-Japan Union Hospital of Jilin University, Changchun, China.
Brain Behav. 2024 Sep;14(9):e3642. doi: 10.1002/brb3.3642.
Depression is widely recognized as a common non-motor symptom of Parkinson's disease (PD). Across different studies, the reported prevalence of depression in PD varies widely, ranging from 2.7% to 90%, but it is unclear whether this association is due to genetic or acquired factors. Whether there is a causal relationship remains unknown. The aim of this study was to use a two-sample Mendelian randomization (MR) approach to investigate the causal effect of PD on depression.
Analyses were conducted separately for individuals of European and East Asian ancestry using publicly available summary data from genome-wide association studies. Depression was divided into two categories: ever depressed for a whole week and major depressive disorder (MDD). PD data were used as the exposure and were obtained from the International Parkinson's Disease Genomics Consortium and the BioBank Japan PheWeb, while depression data were used as the outcome and were obtained from the ntegrative Epidemiology Unit (IEU) Open GWAS Project(A public GWAS database） and the Psychiatric Genomics Consortium. The influence of PD on depression was assessed using inverse variance weighted (IVW), weighted median, MR-Egger, and weighted mode methods. Heterogeneity and pleiotropy were tested, and the results were validated using FinnGen GWAS data from version R9.
In individuals of European ancestry, there was a causal relationship between PD and ever depressed for a whole week (IVW method, odds ratio [OR] = 0.990; 95% CI, 0.984-0.996; p = .002), but no causal relationship was observed between PD and MDD (IVW method, OR = 0.974; 95% CI, 0.942-1.009; p = .141). In individuals of East Asian ancestry, no causal relationship was observed between PD and ever depressed for a whole week (IVW method, OR = 1.001; 95% CI, 0.829-1.209; p = .990) and between PD and MDD (IVW method, OR = 1.017; 95% CI, 0.982-1.052; p = .342). The results of the three additional analysis methods were similar to those of the IVW method, and there was no heterogeneity according to Cochran's Q-test. There was no evidence of pleiotropy based on MR-Egger intercept test and MR-PRESSO. The FinnGen validation dataset supported these findings. The results are stable and reliable.
The observed increase in depression among PD patients could potentially be attributed to modifiable acquired factors. Consequently, there is an urgent need to strengthen the management of PD patients in order to prevent the development of depression in the future.
抑郁症被广泛认为是帕金森病（PD）的一种常见非运动症状。在不同的研究中，PD 患者中抑郁症的报告患病率差异很大，范围从 2.7%到 90%，但尚不清楚这种关联是由于遗传因素还是后天获得的因素。是否存在因果关系仍不清楚。本研究旨在使用两样本孟德尔随机化（MR）方法来研究 PD 对抑郁症的因果影响。
分别使用欧洲和东亚人群的全基因组关联研究的公开汇总数据进行分析。抑郁症分为两类：一周内一直抑郁和重度抑郁症（MDD）。PD 数据被用作暴露因素，来自国际帕金森病遗传学联合会和日本生物银行 PheWeb，而抑郁症数据被用作结果因素，来自综合流行病学单位（IEU）开放 GWAS 项目（一个公共 GWAS 数据库）和精神疾病基因组学联合会。使用逆方差加权（IVW）、加权中位数、MR-Egger 和加权模式方法评估 PD 对抑郁症的影响。检验了异质性和多效性，并使用 FinnGen GWAS 数据版本 R9 进行了验证。
在欧洲血统个体中，PD 与一周内一直抑郁之间存在因果关系（IVW 方法，比值比[OR] = 0.990；95%CI，0.984-0.996；p =.002），但 PD 与 MDD 之间没有因果关系（IVW 方法，OR = 0.974；95%CI，0.942-1.009；p =.141）。在东亚血统个体中，PD 与一周内一直抑郁之间没有因果关系（IVW 方法，OR = 1.001；95%CI，0.829-1.209；p =.990）和 PD 与 MDD 之间没有因果关系（IVW 方法，OR = 1.017；95%CI，0.982-1.052；p =.342）。另外三种分析方法的结果与 IVW 方法相似，根据 Cochran's Q 检验没有异质性。根据 MR-Egger 截距检验和 MR-PRESSO 没有证据表明存在多效性。FinnGen 验证数据集支持这些发现。结果是稳定和可靠的。
PD 患者中观察到的抑郁症增加可能归因于可改变的后天获得因素。因此，迫切需要加强对 PD 患者的管理，以防止未来抑郁症的发生。
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