Dataset Information

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 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.

SUBMITTER: Hao X

PROVIDER: S-EPMC12371002 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature

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

Hao Xiaoyan X Wang Zhiyun Z Feng Yanmei Y Li Mengjie M Hao Chenwei C Liang Yuanyuan Y Zuo Chunyan C Yang Xuhong X Ma Dongrui D Wang YangYang Y Li Shuangjie S Qi Shasha S Sun Yuemeng Y Mao Chengyuan C Sun Shilei S Xu Yuming Y Shi Changhe C

NPJ Parkinson's disease 20250821 1

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 reveal ...[more]

PMID: 40841801

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Project description:Importance. Biological markers of Parkinson’s disease are essential for achieving disease modification. Objective. To determine the association of SNCA blood transcript levels with prevalence of Parkinson’s disease. Background. The SNCA locus is preferentially transcribed in neurons and blood cells. Non-coding genetic variants and neuronal aggregates of α-synuclein protein associate this locus with sporadic Parkinson’s disease and suggest a potential role for abnormal SNCA transcription in the disease mechanism. Here we investigated variation in intracellular SNCA gene expression and SNCA transcript isoform abundance in circulating blood cells of cases with PD and controls in a network of biobanks that represent regional, national, and international populations. Design, Setting, Participants. Three cross-sectional, case-control studies nested in observational biomarker studies. 222 cases with early-stage clinical PD and 183 controls were enrolled from 2005 to 2010 in the Harvard Biomarker Study (HBS) at two Harvard-affiliated tertiary care centers. 76 cases with dopamine transporter imaging (DAT)-confirmed PD and 42 controls were enrolled between August 2007 and December 2008 in the Blood α-Synuclein, Gene Expression and Smell Testing as Diagnostic and Prognostic Biomarkers in Parkinson’s Disease Study (PROBE) study from 22 US tertiary care centers. 202 DAT-confirmed cases with de novo PD and 138 controls were enrolled in the Parkinson’s Progression Markers Initiative (PPMI) between July 2010 and November 2012 from 22 US and international tertiary care centers. Main Outcome Measures. Association of intracellular SNCA transcript abundance with PD estimated on analog and digital expression platforms. Results. Reduced levels of SNCA transcripts were associated with early-stage clinical PD, neuroimaging-confirmed PD, and untreated, neuroimaging-confirmed PD in accessible, peripheral blood cells from a total of 863 individuals. SNCA expression was reduced by 17%, 22%, and 16% in cases compared to controls in the HBS, PROBE, and PPMI study with P values of 0.004, 0.025, and 0.018, respectively, after adjusting for clinical, hematological, and processing covariates. Specific SNCA transcripts with long 3’ untranslated regions (UTR) and those skipping exon 5 are implicated in the accumulation and mitochondrial targeting of α-synuclein protein in Parkinson’s pathology. These transcript isoforms were linked to PD through digital expression analysis. Individuals in the lowest quartile of SNCA expression values had covariate-adjusted odds ratios for PD of 2.14 (95% C. I. 1.1-4.1), 4.5 (95% C. I. 1.3-15), and 2.1 (1.1-4.0) compared to individuals in the highest quartile of expression values in the HBS, PROBE, and PPMI study, respectively. Conclusions and Relevance. Reduced levels of SNCA expression, particularly of disease-relevant transcripts with extended 3’ UTR or exon 5 skipping, are associated with early-stage PD. These findings support a potential role for SNCA as a transcriptional marker of PD and may have implications for patient stratification and risk assessment.

Dataset Information

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

Publications

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

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