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Clinical and Clinical-Pharmacogenetic Models for Prediction of the Most Common Psychiatric Complications Due to Dopaminergic Treatment in Parkinson's Disease.

ABSTRACT: Background: The most common psychiatric complications due to dopaminergic treatment in Parkinson's disease are visual hallucinations and impulse control disorders. Their development depends on clinical and genetic factors.

Methods: We evaluated the simultaneous effect of 16 clinical and 34 genetic variables on the occurrence of visual hallucinations and impulse control disorders. Altogether, 214 Parkinson's disease patients were enrolled. Their demographic, clinical, and genotype data were obtained. Clinical and clinical-pharmacogenetic models were built by The Least Absolute Shrinkage and Selection Operator penalized logistic regression. The predictive capacity was evaluated with the cross-validated area under the receiver operating characteristic curve (AUC).

Results: The clinical-pharmacogenetic index for prediction of visual hallucinations encompassed age at diagnosis (OR?=?0.99), rapid eye movement (REM) sleep behavior disorder (OR?=?2.27), depression (OR?=?1.0002), IL6 rs1800795 (OR?=?0.99), GPX1 s1050450 (OR?=?1.07), COMT rs165815 (OR?=?0.69), MAOB rs1799836 (OR?=?0.97), DRD3 rs6280 (OR?=?1.32), and BIRC5 rs8073069 (OR?=?0.94). The clinical-pharmacogenetic index for prediction of impulse control disorders encompassed age at diagnosis (OR?=?0.95), depression (OR?=?1.75), beta-blockers (OR?=?0.99), coffee consumption (OR?=?0.97), NOS1 rs2682826 (OR?=?1.15), SLC6A3 rs393795 (OR?=?1.27), SLC22A1 rs628031 (OR?=?1.19), DRD2 rs1799732 (OR?=?0.88), DRD3 rs6280 (OR?=?0.88), and NRG1 rs3924999 (OR?=?0.96). The cross-validated AUCs of clinical and clinical-pharmacogenetic models for visual hallucinations were 0.60 and 0.59, respectively. The AUCs of clinical and clinical-pharmacogenetic models for impulse control disorders were 0.72 and 0.71, respectively. The AUCs show that the addition of selected genetic variables to the analysis does not contribute to better prediction of visual hallucinations and impulse control disorders.

Conclusions: Models could be improved by a larger cohort and by addition of other types of Parkinson's disease biomarkers to the analysis.

SUBMITTER: Redensek S

PROVIDER: S-EPMC7689202 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Clinical and Clinical-Pharmacogenetic Models for Prediction of the Most Common Psychiatric Complications Due to Dopaminergic Treatment in Parkinson's Disease.

Redenšek Sara S Jenko Bizjan Barbara B Trošt Maja M Dolžan Vita V

The international journal of neuropsychopharmacology 20201101 8

<h4>Background</h4>The most common psychiatric complications due to dopaminergic treatment in Parkinson's disease are visual hallucinations and impulse control disorders. Their development depends on clinical and genetic factors.<h4>Methods</h4>We evaluated the simultaneous effect of 16 clinical and 34 genetic variables on the occurrence of visual hallucinations and impulse control disorders. Altogether, 214 Parkinson's disease patients were enrolled. Their demographic, clinical, and genotype da ...[more]

PMID: 32710539

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Project description:The response to dopaminergic treatment in Parkinson's disease depends on many clinical and genetic factors. The very common motor fluctuations (MF) and dyskinesia affect approximately half of patients after 5 years of treatment with levodopa. We did an evaluation of a combined effect of 16 clinical parameters and 34 single nucleotide polymorphisms to build clinical and clinical-pharmacogenetic models for prediction of time to occurrence of motor complications and to compare their predictive abilities. In total, 220 Parkinson's disease patients were included in the analysis. Their demographic, clinical, and genotype data were obtained. The combined effect of clinical and genetic factors was assessed using The Least Absolute Shrinkage and Selection Operator penalized regression in the Cox proportional hazards model. Clinical and clinical-pharmacogenetic models were constructed. The predictive capacity of the models was evaluated with the cross-validated area under time-dependent receiver operating characteristic curve. Clinical-pharmacogenetic model included age at diagnosis (HR = 0.99), time from diagnosis to initiation of levodopa treatment (HR = 1.24), COMT rs165815 (HR = 0.90), DRD3 rs6280 (HR = 1.03), and BIRC5 rs9904341 (HR = 0.95) as predictive factors for time to occurrence of MF. Furthermore, clinical-pharmacogenetic model for prediction of time to occurrence of dyskinesia included female sex (HR = 1.07), age at diagnosis (HR = 0.97), tremor-predominant Parkinson's disease (HR = 0.88), beta-blockers (HR = 0.95), alcohol consumption (HR = 0.99), time from diagnosis to initiation of levodopa treatment (HR = 1.15), CAT rs1001179 (HR = 1.27), SOD2 rs4880 (HR = 0.95), NOS1 rs2293054 (HR = 0.99), COMT rs165815 (HR = 0.92), and SLC22A1 rs628031 (HR = 0.80). Areas under the curves for clinical and clinical-pharmacogenetic models for MF after 5 years of levodopa treatment were 0.68 and 0.70, respectively. Areas under the curves for clinical and clinical-pharmacogenetic models for dyskinesia after 5 years of levodopa treatment were 0.71 and 0.68, respectively. These results show that clinical-pharmacogenetic models do not have better ability to predict time to occurrence of motor complications in comparison to the clinical ones despite the significance of several polymorphisms. Models could be improved by a larger sample size and by additional polymorphisms, epigenetic predictors or serum biomarkers.

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Dataset Information

Clinical and Clinical-Pharmacogenetic Models for Prediction of the Most Common Psychiatric Complications Due to Dopaminergic Treatment in Parkinson's Disease.

Publications

Clinical and Clinical-Pharmacogenetic Models for Prediction of the Most Common Psychiatric Complications Due to Dopaminergic Treatment in Parkinson's Disease.

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