Abstract
The serotonergic system is important in Parkinson’s disease (PD) pathogenesis as it can take over dopamine production after a large portion of dopaminergic neurons is lost through neurodegeneration. The aim of this study was to evaluate the effect of genetic variability of serotonergic genes on the occurrence of motor complications and psychiatric adverse events (AE) due to dopaminergic treatment. We enrolled 231 patients and their clinical data were collected. Genotyping was performed for eight genetic variants. Logistic regression was used for analysis. Carriers of the HTR1A rs6295 GC genotype (OR = 2.58; 95% CI = 1.15–5.78; p = 0.021), TPH2 rs4290270 AA genotype (OR = 2.78; 95% CI = 1.08–7.03; p = 0.034), and at least one TPH2 rs4570625 T allele (OR = 1.86; 95% CI = 1.00–3.44; p = 0.047) had increased risk for visual hallucinations (VH). Additionally, carriers of at least one SLC6A4 5-HTTPLR rs25531 S (OR = 0.52; 95% CI = 0.28–0.96; p = 0.037) or at least one LG allele (OR = 0.37; 95% CI = 0.14–0.97; p = 0.044) had a decreased chance for VH. Constructed haplotypes of the TPH2 showed increased risk for VH (OR = 1.94; 95% CI = 1.06–3.55; p = 0.032) and impulse control disorders (OR = 5.20; 95% CI = 1.86–14.50; p = 0.002). Finally, individual gene–gene interactions showed decreased odds for the development of motor AE. Our findings suggest that the serotonergic pathway may play an important role in the development of AE resulting from dopaminergic treatment.
Highlights
Serotonin is a monoamine with an integral role in the human body as a neurotransmitter in the central nervous system, and as a signaling molecule in the periphery [1]
The associations described above were adjusted for (1) age at diagnosis for visual hallucinations (VH) and (2) age at diagnosis and treatment with dopamine agonists (DA) for impulse control disorders (ICD) as we have previously reported that these clinical parameters were significantly associated with assessed adverse events (AE) [28]
In the present study we tested the associations between seven common functional genetic variants in four serotonergic pathway genes and the AE related to dopaminergic treatment of Parkinson’s disease (PD)
Summary
Serotonin is a monoamine with an integral role in the human body as a neurotransmitter in the central nervous system, and as a signaling molecule in the periphery [1]. It is important in many different aspects of brain activity, such as mood, memory, emotion, sleep, appetite, and motor activity [2]. Alpha-synuclein, the misfolded protein deposited in the brain of PD patients, can be found in dopaminergic neurons2,obfu13t in serotonergic neurons of raphe nuclei as well.
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