Сlinical and genetic predictors of anxiety in patients with Parkinson's disease

Parkinson’s disease (PD) is a chronic progressive neurodegenerative disorder primarily associated with dopamine deficiency in the central nervous system, accompanied by the development of both motor and non-motor symptoms. Neuropsychiatric symptoms, as a subset of non-motor manifestations, play a major role in disease burden and reduced quality of life in patients. One of the leading symptoms in this category is anxiety, which develops not only as a psychological reaction to the disease but is mainly caused by neurotransmitter dysfunctions (dopaminergic, noradrenergic, serotonergic, and GABAergic dysfunctions in the striatum, limbic system, and thalamus). It is also suggested that anxiety in PD may be associated with genetic factors. Objective: To examine the predictive role of clinical manifestations and genetic biomarkers (Val66Met mutation in the BDNF gene and Ser9Gly mutation in the DRD3 gene) in the development of anxiety in Parkinson’s disease. The study included 130 patients with Parkinson’s disease, who were divided into two groups based on the presence of anxiety. The first group consisted of 33 PD patients with anxiety, with a median age of 67.0 [60.0; 71.5] years. The second group included 97 patients without anxiety, with a median age of 67.0 [61.0; 72.5] years. Standardized scales were used to assess motor and non-motor symptoms. Frequencies were used to describe nominal data. Pearson’s χ² test was applied to compare two or more independent groups of nominal data. Quantitative data were presented as medians with interquartile ranges, and the Mann–Whitney U test was used for comparisons. Differences were considered statistically significant at p ≤ 0.05. The patients with PD and anxiety had a longer history of the disease, high levels of depression, frequent presence of non-motor symptoms and a lower quality of life. The motor deficit in the 3rd part of the UPDRS scale in patients with anxiety was 41.0 [31.50; 48.50] points versus 35.0 [21.0; 44.50] points in patients without anxiety (p = 0.047). On the contrary, there were no differences in cognitive status and daytime sleepiness between the two groups of patients. As a result of a molecular genetic study, a statistically significant predominance of TC and CC genotypes of rs6280 polymorphism of the DRD3 gene (c.25G>A p.Gly9Ser) and GA and AA genotypes of rs6265 polymorphism of the BDNF gene was revealed in patients with PD and anxiety. As a result of this study, it was revealed that the development of anxiety in Parkinson’s disease is influenced by the length of the disease, depression, the number of non-motor symptoms, and motor deficiency. In addition, the patients with anxiety were characterized by a lower quality of life than the patients whose anxiety was not detected. As for the genetic basis, our study indicates the contribution of polymorphic variants of the DRD3 (rs6280) and BDNF (rs6265) genes to the development of anxiety in PD.