Serotonin-Related Functional Genetic Variants Affect the Occurrence of Psychiatric and Motor Adverse Events of Dopaminergic Treatment in Parkinson's Disease: A Retrospective Cohort Study

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 L-G 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.