Association between anxiety disorder, anxiolytic drugs, and risk of incident Parkinson’s disease

Abstract In this prospective cohort study, we analysed data from 502,364 participants (ages 40–69) in the UK Biobank, with follow-up until 2024. Logistic and Cox regression analysis identified generalized anxiety disorder (GAD) and obsessive-compulsive disorder (OCD) as independent risk factors for...

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Main Authors: Xiaoyan Hao, Zhiyun Wang, Yanmei Feng, Mengjie Li, Chenwei Hao, Yuanyuan Liang, Chunyan Zuo, Xuhong Yang, Dongrui Ma, YangYang Wang, Shuangjie Li, Shasha Qi, Yuemeng Sun, Chengyuan Mao, Shilei Sun, Yuming Xu, Changhe Shi
Format: Article
Language:English
Published: Nature Portfolio 2025-08-01
Series:npj Parkinson's Disease
Online Access:https://doi.org/10.1038/s41531-025-01104-x
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author Xiaoyan Hao
Zhiyun Wang
Yanmei Feng
Mengjie Li
Chenwei Hao
Yuanyuan Liang
Chunyan Zuo
Xuhong Yang
Dongrui Ma
YangYang Wang
Shuangjie Li
Shasha Qi
Yuemeng Sun
Chengyuan Mao
Shilei Sun
Yuming Xu
Changhe Shi
author_facet Xiaoyan Hao
Zhiyun Wang
Yanmei Feng
Mengjie Li
Chenwei Hao
Yuanyuan Liang
Chunyan Zuo
Xuhong Yang
Dongrui Ma
YangYang Wang
Shuangjie Li
Shasha Qi
Yuemeng Sun
Chengyuan Mao
Shilei Sun
Yuming Xu
Changhe Shi
author_sort Xiaoyan Hao
collection DOAJ
description Abstract In this prospective cohort study, we analysed data from 502,364 participants (ages 40–69) in the UK Biobank, with follow-up until 2024. Logistic and Cox regression analysis identified generalized anxiety disorder (GAD) and obsessive-compulsive disorder (OCD) as independent risk factors for Parkinson’s disease (PD), with post-traumatic stress disorder (PTSD) patients under 71 also at increased risk. Panic disorder (PAD) showed no association with PD. Further analysis of anxiolytic drug use revealed that selective serotonin reuptake inhibitors (SSRIs), benzodiazepines (BDZs), medium-to-high frequency use of tricyclic antidepressants (TCAs) and serotonin norepinephrine reuptake inhibitors (SNRIs) were linked to PD incidence, while low-frequency use of TCAs and SNRIs was not. Mediation analysis indicated that GAD influenced PD risk through the thalamus, brainstem, and left putamen, while OCD and PTSD affected PD risk via brain regions including the angular gyrus, thalamus, and postcentral gyrus. These findings provide novel insights into PD mechanisms and potential therapeutic targets.
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language English
publishDate 2025-08-01
publisher Nature Portfolio
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series npj Parkinson's Disease
spelling doaj-art-5a8afac7dfb5454ebbb03ddd0b51b33a2025-08-24T11:14:43ZengNature Portfolionpj Parkinson's Disease2373-80572025-08-0111111010.1038/s41531-025-01104-xAssociation between anxiety disorder, anxiolytic drugs, and risk of incident Parkinson’s diseaseXiaoyan Hao0Zhiyun Wang1Yanmei Feng2Mengjie Li3Chenwei Hao4Yuanyuan Liang5Chunyan Zuo6Xuhong Yang7Dongrui Ma8YangYang Wang9Shuangjie Li10Shasha Qi11Yuemeng Sun12Chengyuan Mao13Shilei Sun14Yuming Xu15Changhe Shi16Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityNurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology, Department of Radiology, Zhongda Hospital, Medical School, Southeast UniversityDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityDepartment of Pain Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityAbstract In this prospective cohort study, we analysed data from 502,364 participants (ages 40–69) in the UK Biobank, with follow-up until 2024. Logistic and Cox regression analysis identified generalized anxiety disorder (GAD) and obsessive-compulsive disorder (OCD) as independent risk factors for Parkinson’s disease (PD), with post-traumatic stress disorder (PTSD) patients under 71 also at increased risk. Panic disorder (PAD) showed no association with PD. Further analysis of anxiolytic drug use revealed that selective serotonin reuptake inhibitors (SSRIs), benzodiazepines (BDZs), medium-to-high frequency use of tricyclic antidepressants (TCAs) and serotonin norepinephrine reuptake inhibitors (SNRIs) were linked to PD incidence, while low-frequency use of TCAs and SNRIs was not. Mediation analysis indicated that GAD influenced PD risk through the thalamus, brainstem, and left putamen, while OCD and PTSD affected PD risk via brain regions including the angular gyrus, thalamus, and postcentral gyrus. These findings provide novel insights into PD mechanisms and potential therapeutic targets.https://doi.org/10.1038/s41531-025-01104-x
spellingShingle Xiaoyan Hao
Zhiyun Wang
Yanmei Feng
Mengjie Li
Chenwei Hao
Yuanyuan Liang
Chunyan Zuo
Xuhong Yang
Dongrui Ma
YangYang Wang
Shuangjie Li
Shasha Qi
Yuemeng Sun
Chengyuan Mao
Shilei Sun
Yuming Xu
Changhe Shi
Association between anxiety disorder, anxiolytic drugs, and risk of incident Parkinson’s disease
npj Parkinson's Disease
title Association between anxiety disorder, anxiolytic drugs, and risk of incident Parkinson’s disease
title_full Association between anxiety disorder, anxiolytic drugs, and risk of incident Parkinson’s disease
title_fullStr Association between anxiety disorder, anxiolytic drugs, and risk of incident Parkinson’s disease
title_full_unstemmed Association between anxiety disorder, anxiolytic drugs, and risk of incident Parkinson’s disease
title_short Association between anxiety disorder, anxiolytic drugs, and risk of incident Parkinson’s disease
title_sort association between anxiety disorder anxiolytic drugs and risk of incident parkinson s disease
url https://doi.org/10.1038/s41531-025-01104-x
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