Objective: This study aimed to examine the association of seven selected polymorphisms of DRD2, ANKK1, COMT and DAT genes with Parkinson’s disease psychosis (PDP) onset. Another objective was to explore demographic and clinical correlates of PDP.

Background: Recent studies explored polymorphisms of multiple genes as possible genetic substrate of PDP.

Method: The study included 234 PD patients who were treated with levodopa for at least two years. A comprehensive set of clinical scales was applied in all patients.  Genotyping of rs4680 in COMT, rs6277, rs1076560, and rs2283265 in DRD2, rs1800497 and rs2734849 in ANKK1 genes as well as detection of variable number of tandem repeats (VNTR) polymorphism in the DAT gene was performed.

Results: Out of 234 PD patients, 101 (43.2%) patients met diagnostic criteria for PDP. PDP patients had significant higher total scores of UPDRS, as well as higher scores of UPDRS subscales, HDRS, HARS and NMSQuest scores compared to non-PDP group. MMSE scores were lower among PPD patients compared to non-PPD group.  More advanced HY stage has 3.7 times higher risk for PDP. Also, we found higher risk of developing psychosis 2.3 times in AA rs6277 DRD2 carriers and 2.2 times higher risk in GG rs2734849 ANKK1 carriers (p=0.027, and p=0.031 respectively). Multivariate regression analysis demonstrated that independent predictors of the onset of PDP were: LEDD ≥ 900mg (OR=2.041, 95%CI: 1.089-3.824, p=0.026), UPDRS III part score (OR=1.025, 95%CI: 1.001-1.050, p=0.044), HDRS score ≥7 (OR=2.846, 95%CI: 1.289-6.286, p=0.010), HARS score>14 (OR=2.236, 95%CI: 1.061-4.710, p=0.034) and GG homozygotes of  rs2734849 ANKK1 gene (OR=2.588, 95%CI: 1.325-5.054, p=0.005).

Conclusion: We found that rs6277 of DRD2 gene and rs2734848 of ANKK1 gene are associated with PDP. The presence of AA rs6277 DRD2 is associated with 2.3 times and GG rs2734849 ANKK1 2.2 times higher risk for PDP development. In addition, LEDD≥900mg/day, motor status, depression, and anxiety, as well as GG genotype of rs2734849 ANKK1 were independent factors of PDP, whereas age, disease duration, MMSE score, and average levodopa doses were not. We found that depression was the strongest independent risk factor that almost 3 times increases the risk of PDP.

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