ppanPersonalized Psychiatry and NeurologyPersonalized Psychiatry and Neurology2712-9179V. M. Bekhterev National Medical Research Centre for Psychiatry and Neurology of the Ministry of Health of the Russian Federation (Bekhterev NMRC PN)10.52667/2712-9179-2025-5-1-32-44ppan-129Research ArticleARTICLESingle-Nucleotide Variant rs167771 of the DRD3 Gene Does Not Increase the Risk of Developing Antipsychotic-Induced Parkinsonism in Schizophrenic PatientsNasyrovaR. F.

Regina F. Nasyrova

192019 Saint Petersburg

300012 Tula

regina_nmrcpn@mail.ruShnayderN. A.

Natalia A. Shnayder

192019 Saint Petersburg

Tel.: +7-(812)-670-02-20 (ext. 7814)

660022 Krasnoyarsk

naschnaider@yandex.ruBoikoI. R.

Irina R. Boiko

192019 Saint Petersburg

PetrovaM. M.

Marina M. Petrova

660022 Krasnoyarsk

ShipullinG. A.

German A. Shipullin

125310 Moscow

ChumakovaG. A.

Galina A. Chumakova

656038 Barnaul

GarganeevaN. P.

Natalia P. Garganeeva

634050 Tomsk

V. M. Bekhterev National Medical Research Centre for Psychiatry and Neurology; Tula State UniversityRussian FederationV. M. Bekhterev National Medical Research Centre for Psychiatry and Neurology; V. F. Voino-Yasenetsky Krasnoyarsk State Medical UniversityRussian FederationV. M. Bekhterev National Medical Research Centre for Psychiatry and NeurologyRussian FederationV. F. Voino-Yasenetsky Krasnoyarsk State Medical UniversityRussian FederationShipullinRussian FederationChumakovaRussian FederationGarganeevaRussian Federation202517032025513244Copyright © Nasyrova R.F., Shnayder N.A., Boiko I.R., Petrova M.M., Shipullin G.A., Chumakova G.A., Garganeeva N.P., 20252025Nasyrova R.F., Shnayder N.A., Boiko I.R., Petrova M.M., Shipullin G.A., Chumakova G.A., Garganeeva N.P.Nasyrova R.F., Shnayder N.A., Boiko I.R., Petrova M.M., Shipullin G.A., Chumakova G.A., Garganeeva N.P.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.jppn.ru/jour/article/view/129

Antipsychotic-induced parkinsonism (AIP) is a form of secondary parkinsonism that most often develops with blockade of dopaminergic receptors type D2. However, AIP can oc-cur not only while taking first-generation APs, but also new ones that have a wider receptor pro-file. There is a connection between the DRD3 gene and the regulation of motor activity in associa-tion genetic studies of AIP; Aim: to study the role of single-nucleotide variant rs167771 of the DRD3 gene, encoding dopaminergic receptors D3 type, with the risk of AIP in Caucasian patients with schizophrenia spectrum disorders (SSDs) of North-West Russia; Methods: The study in-volved 91 participants permanently residing in Saint Petersburg and the Leningrad region (North-West Russia), including: group 1 - 30 patients (SSDs with AIP); group 2 - 29 patients (SSDs without AIP); group 3 (control) - 32 healthy volunteers. All participants underwent: a neurological exami-nation using scales and questionnaires (H&Y, MoCa, UPDRS, BARS, AIMS, ESRS) at two points (before and after 8 weeks on AP monotherapy) and an association genetic study of carriage of major and minor alleles and genotypes of rs167771 of the DRD3 gene with a risk of developing AIP; Results: According to the study, it was shown that AIP is characterized by bradykinesia with a decrease in the amplitude of multidirectional movements. Mild/moderate asymmetry in the severity of action tremor according to the hemi-type on the left. The allelic frequency of the stud-ied rs167771 of the DRD3 gene in Caucasians of North-West Russia was comparable to that in the countries of Northern Europe, also in the countries of Southeast Asia and some regions of North and South America. The obtained clinical data are typical for the early stage of development of AIP, which is missed in more than 80% of cases by the 8th week from the start of taking AP. The major allele A of rs167771 of the DRD3 gene is protective against the risk of SSDs (OR < 0.001), but not AIP (OR > 0.05); Conclusions: We have not found a significant association of rs167771 of the DRD3 gene with the risk of developing AIP in Caucasians in North-West Russia.

antipsychotic-induced parkinsonismgene DRD3rs167771dopaminergic receptorReferencesVaiman, E.E.; Shnayder, N.A.; Khasanova A.K.; Strelnik A.I.; Gayduk, A.J.; Al-Zamil, M. et al. Pathophysiological mechanisms of antipsychotic-induced parkinsonism. Biomedicines 2022, 10(8):2010. doi:10.3390/biomedicines10082010Vaiman, E.E.; Shnayder, N.A.; Khasanova A.K.; Strelnik A.I.; Gayduk, A.J.; Al-Zamil, M. et al. Pathophysiological mechanisms of antipsychotic-induced parkinsonism. Biomedicines 2022, 10(8):2010. doi:10.3390/biomedicines10082010Vaiman, E.E.; Shnayder, N.A.; Neznanov, N.G.; Nasyrova R.F. Drug-induced parkinsonism. Social and Clinical Psychiatry 2021, 31(1):96-103.Vaiman, E.E.; Shnayder, N.A.; Neznanov, N.G.; Nasyrova R.F. Drug-induced parkinsonism. Social and Clinical Psychiatry 2021, 31(1):96-103.Shin, H.W.; Chung S.J. Drug-induced parkinsonism. J Clin Neurol 2012, 8(1):15-21. doi:10.3988/jcn.2012.8.1.15Shin, H.W.; Chung S.J. Drug-induced parkinsonism. J Clin Neurol 2012, 8(1):15-21. doi:10.3988/jcn.2012.8.1.15Vaiman, E.E.; Novitsky, M.A.; Nasyrova R.F. Pharmacogenetics of chlorpromazine and its role in the development of antipsychotic-induced parkinsonism. Personalized Psychiatry and Neurology 2021, 1(1):11-17. doi:10.52667/2712-9179-2021-1-1-11-17Vaiman, E.E.; Novitsky, M.A.; Nasyrova R.F. Pharmacogenetics of chlorpromazine and its role in the development of antipsychotic-induced parkinsonism. Personalized Psychiatry and Neurology 2021, 1(1):11-17. doi:10.52667/2712-9179-2021-1-1-11-17Kirichenko, E.N. Gene DRD3: [Electronic resource]. GENOCARD Genetic Encyclopedia. 2020. – URL: https://www.genokarta.ru/gene/DRD3Kirichenko, E.N. Gene DRD3: [Electronic resource]. GENOCARD Genetic Encyclopedia. 2020. – URL: https://www.genokarta.ru/gene/DRD3Schwartz, J.C.; Levesque, D.; Martres, M.P.; Sokoloff, P. Dopamine D3 receptor: basic and clinical aspects. Clin. Neuropharmacol. 1993, 16:295–314Schwartz, J.C.; Levesque, D.; Martres, M.P.; Sokoloff, P. Dopamine D3 receptor: basic and clinical aspects. Clin. Neuropharmacol. 1993, 16:295–314Magistrelli, L.; Ferrari, M.; Furgiuele, A.; Milner, A.V.; Contaldi, E.; Comi, C.; et al. Polymorphisms of dopamine receptor genes and Parkinson’s disease: clinical relevance and future perspectives. Int. J. Mol. Sci. 2021, 22:3781. doi:10.3390/ijms22073781Magistrelli, L.; Ferrari, M.; Furgiuele, A.; Milner, A.V.; Contaldi, E.; Comi, C.; et al. Polymorphisms of dopamine receptor genes and Parkinson’s disease: clinical relevance and future perspectives. Int. J. Mol. Sci. 2021, 22:3781. doi:10.3390/ijms22073781Ivanova, S.A.; Alifirova, V.M.; Zhukova, I.A.; Boyko, A.S.; Fedorenko, O.Iu.; Zhukova, N.G.; Bokhan, N.A. The association of the DRD3 gene with Parkinson’s disease. S.S. Korsakov Journal of Neurology and Psychiatry. 2016, 116(5):71‑74. doi:10.17116/jnevro20161165171-74Ivanova, S.A.; Alifirova, V.M.; Zhukova, I.A.; Boyko, A.S.; Fedorenko, O.Iu.; Zhukova, N.G.; Bokhan, N.A. The association of the DRD3 gene with Parkinson’s disease. S.S. Korsakov Journal of Neurology and Psychiatry. 2016, 116(5):71‑74. doi:10.17116/jnevro20161165171-74Bakker, P.R.; Al Hadithy, A.F.Y.; Amin, N.; van Duijn, C.M.; van Os, J. et al. Antipsychotic-induced movement disorders in long-stay psychiatric patients and 45 Tag SNPs in 7 candidate genes: a prospective study. PLoS ONE 2012, 7(12):e50970. doi: 10.1371/journal.pone.0050970Bakker, P.R.; Al Hadithy, A.F.Y.; Amin, N.; van Duijn, C.M.; van Os, J. et al. Antipsychotic-induced movement disorders in long-stay psychiatric patients and 45 Tag SNPs in 7 candidate genes: a prospective study. PLoS ONE 2012, 7(12):e50970. doi: 10.1371/journal.pone.0050970Tsermpini, E.E.; Redenšek, S.; Dolžan, V. Genetic factors associated with tardive dyskinesia: From pre-clinical models to clinical studies. Front. Pharmacol. 2022, 12:834129. doi:10.3389/fphar.2021.834129Tsermpini, E.E.; Redenšek, S.; Dolžan, V. Genetic factors associated with tardive dyskinesia: From pre-clinical models to clinical studies. Front. Pharmacol. 2022, 12:834129. doi:10.3389/fphar.2021.834129Pozhidaev, I.; Alifirova, V.M.; Freidin, M.B.; Zhukova, I.A.; Fedorenko, O.Y.; Osmanova, D.Z.; et al. Dopamine receptors genes polymorphisms in Parkinson patients with levodopa-induced dyskinesia. European Neuropsychopharmacology 2017, 27(S4):S590. doi:10.1016/S0924-977X(17)31129-XPozhidaev, I.; Alifirova, V.M.; Freidin, M.B.; Zhukova, I.A.; Fedorenko, O.Y.; Osmanova, D.Z.; et al. Dopamine receptors genes polymorphisms in Parkinson patients with levodopa-induced dyskinesia. European Neuropsychopharmacology 2017, 27(S4):S590. doi:10.1016/S0924-977X(17)31129-XGassó, P.; Mas, S.; Bernardo, M.; Alvarez, S.; Parellada, E.; Lafuente, A. A common variant in DRD3 gene is associated with risperidone-induced extrapyramidal symptoms. Pharmacogenomics J. 2009, 9(6): 404-410. doi:10.1038/tpj.2009.26Gassó, P.; Mas, S.; Bernardo, M.; Alvarez, S.; Parellada, E.; Lafuente, A. A common variant in DRD3 gene is associated with risperidone-induced extrapyramidal symptoms. Pharmacogenomics J. 2009, 9(6): 404-410. doi:10.1038/tpj.2009.26Zhi, Y.; Yuan, Y.; Si, Q. The association between DRD3 Ser9Gly polymorphism and depression severity in Parkinson's disease. Parkinsons Dis. 2019, 2019:1642087. doi:10.1155/2019/1642087Zhi, Y.; Yuan, Y.; Si, Q. The association between DRD3 Ser9Gly polymorphism and depression severity in Parkinson's disease. Parkinsons Dis. 2019, 2019:1642087. doi:10.1155/2019/1642087Aguiar-Pulido, V.; Seoane, J.A.; Rabuñal, J.R.; Dorado, J.; Pazos, A.; Munteanu, C.R. Machine learning techniques for single nucleotide polymorphism – disease classification models in schizophrenia. Molecules. 2010, 15(7):4875-4889. doi:10.3390/molecules15074875Aguiar-Pulido, V.; Seoane, J.A.; Rabuñal, J.R.; Dorado, J.; Pazos, A.; Munteanu, C.R. Machine learning techniques for single nucleotide polymorphism – disease classification models in schizophrenia. Molecules. 2010, 15(7):4875-4889. doi:10.3390/molecules15074875Staal, W.G.; Langen, M.; van Dijk, S.; Mensen, V.T.; Durston, S. DRD3 gene and striatum in autism spectrum disorder. Br J Psychiatry. 2015, 206(5):431-432. doi:10.1192/bjp.bp.114.148973Staal, W.G.; Langen, M.; van Dijk, S.; Mensen, V.T.; Durston, S. DRD3 gene and striatum in autism spectrum disorder. Br J Psychiatry. 2015, 206(5):431-432. doi:10.1192/bjp.bp.114.148973Le Foll, B.; Goldberg, S.R.; Sokoloff, P. The dopamine D3 receptor and drug dependence: effects on reward or beyond? Neuropharmacology. 2005, 49(4):525-541. doi:10.1016/j.neuropharm.2005.04.022Le Foll, B.; Goldberg, S.R.; Sokoloff, P. The dopamine D3 receptor and drug dependence: effects on reward or beyond? Neuropharmacology. 2005, 49(4):525-541. doi:10.1016/j.neuropharm.2005.04.022Ye, J.; Ji, F.; Jiang, D.; et al. Polymorphisms in dopaminergic genes in schizophrenia and their implications in motor deficits and antipsychotic treatment. Front Neurosci. 2019, 13:355. doi:10.3389/fnins.2019.00355Ye, J.; Ji, F.; Jiang, D.; et al. Polymorphisms in dopaminergic genes in schizophrenia and their implications in motor deficits and antipsychotic treatment. Front Neurosci. 2019, 13:355. doi:10.3389/fnins.2019.00355Sample Size Calculator. Available online: URL https://clincalc.com/stats/samplesize.aspx (accessed on 12/27/2023).Sample Size Calculator. Available online: URL https://clincalc.com/stats/samplesize.aspx (accessed on 12/27/2023).Altman DG. How large a sample? In: Gore SM, Altman DG (eds.). Statistics in Practice. London, UK: British Medical Association. 1982: 100.Altman DG. How large a sample? In: Gore SM, Altman DG (eds.). Statistics in Practice. London, UK: British Medical Association. 1982: 100.Narkevich, A.N.; Vinogradov, K.A. Methods for determining the minimum required sample size in medical research. Social Aspects of Population Health. 2019, 65(6):10. doi:10.21045/2071-5021-2019-65-6-10Narkevich, A.N.; Vinogradov, K.A. Methods for determining the minimum required sample size in medical research. Social Aspects of Population Health. 2019, 65(6):10. doi:10.21045/2071-5021-2019-65-6-10Ivey, F.M.; Katzel, L.I.; Sorkin, J.D.; Macko, R.F.; Shulman, L.M. The Unified Parkinson's Disease Rating Scale as a predictor of peak aerobic capacity and ambulatory function. J Rehabil Res Dev. 2012, 49(8):1269-76. doi:10.1682/jrrd.2011.06.0103Ivey, F.M.; Katzel, L.I.; Sorkin, J.D.; Macko, R.F.; Shulman, L.M. The Unified Parkinson's Disease Rating Scale as a predictor of peak aerobic capacity and ambulatory function. J Rehabil Res Dev. 2012, 49(8):1269-76. doi:10.1682/jrrd.2011.06.0103Chouinard, G.; Margolese, H.C. Manual for the Extrapyramidal Symptom Rating Scale (ESRS). Schizophrenia research 2005, 76(2-3):247–265. doi:10.1016/j.schres.2005.02.013Chouinard, G.; Margolese, H.C. Manual for the Extrapyramidal Symptom Rating Scale (ESRS). Schizophrenia research 2005, 76(2-3):247–265. doi:10.1016/j.schres.2005.02.013Opara, J.; Małecki, A.; Małecka, E.; Socha, T. Motor assessment in Parkinson`s disease. Annals of agricultural and environmental medicine: AAEM 2017, 24(3):411–415. doi:10.5604/12321966.1232774Opara, J.; Małecki, A.; Małecka, E.; Socha, T. Motor assessment in Parkinson`s disease. Annals of agricultural and environmental medicine: AAEM 2017, 24(3):411–415. doi:10.5604/12321966.1232774Rai, N.K.; Goyal, V.; Kumar, N.; Shukla, G.; Srivastava, A.K.; Singh, S.; Behari, M. Neuropsychiatric co-morbidities in non-demented Parkinson's disease. Annals of Indian Academy of Neurology 2015, 18(1):33–38. doi:10.4103/0972-2327.144287Rai, N.K.; Goyal, V.; Kumar, N.; Shukla, G.; Srivastava, A.K.; Singh, S.; Behari, M. Neuropsychiatric co-morbidities in non-demented Parkinson's disease. Annals of Indian Academy of Neurology 2015, 18(1):33–38. doi:10.4103/0972-2327.144287Dautzenberg, G; Lijmer, J; Beekman, A. Diagnostic accuracy of the Montreal Cognitive Assessment (MoCA) for cognitive screening in old age psychiatry: determining cutoff scores in clinical practice. Avoiding spectrum bias caused by healthy controls. Int J Geriatr Psychiatry. 2020, 35(3):261-269. doi:10.1002/gps.5227Dautzenberg, G; Lijmer, J; Beekman, A. Diagnostic accuracy of the Montreal Cognitive Assessment (MoCA) for cognitive screening in old age psychiatry: determining cutoff scores in clinical practice. Avoiding spectrum bias caused by healthy controls. Int J Geriatr Psychiatry. 2020, 35(3):261-269. doi:10.1002/gps.5227Barnes, T.R. A rating scale for drug-induced akathisia. Br J Psychiatry. 1989, 154:672–676.Barnes, T.R. A rating scale for drug-induced akathisia. Br J Psychiatry. 1989, 154:672–676.Barnes, T.R. The Barnes Akathisia Rating Scale - revisited. J Psychopharmacol. 2003, 17(4):365–370.Barnes, T.R. The Barnes Akathisia Rating Scale - revisited. J Psychopharmacol. 2003, 17(4):365–370.Abnormal Involuntary Movement Scale (AIMS). Psychopharmacol Bull. 1988, 24(4):781–783.Abnormal Involuntary Movement Scale (AIMS). Psychopharmacol Bull. 1988, 24(4):781–783.Salamaikina, S.; Karnaushkina, M.; Korchagin, V.; Litvinova, M.; Mironov, K; Akimkin, V. TLRs gene polymorphisms associated with pneumonia before and during COVID-19 pandemic. Diagnostics 2023, 13:121. doi:10.3390/diagnostics13010121Salamaikina, S.; Karnaushkina, M.; Korchagin, V.; Litvinova, M.; Mironov, K; Akimkin, V. TLRs gene polymorphisms associated with pneumonia before and during COVID-19 pandemic. Diagnostics 2023, 13:121. doi:10.3390/diagnostics13010121Shnayder, N.A.; Vaiman, E.E.; Neznanov, N.G.; Nasyrova, R.F. Pharmacogenetics of antipsychotic-induced extrapyramidal disorders. 1st ed.; Publisher: DEAN Publishing House, Russia, St. Petersburg, 2022, р.288 p. ISBN 978-5-6046354-7-6Shnayder, N.A.; Vaiman, E.E.; Neznanov, N.G.; Nasyrova, R.F. Pharmacogenetics of antipsychotic-induced extrapyramidal disorders. 1st ed.; Publisher: DEAN Publishing House, Russia, St. Petersburg, 2022, р.288 p. ISBN 978-5-6046354-7-6Geography of Genetic Variants Browser. Available online: URL https://popgen.uchicago.edu/ggv/?data=%221000genomes%22&chr=11&pos=113270828 (accessed on 12/27/2023).Geography of Genetic Variants Browser. Available online: URL https://popgen.uchicago.edu/ggv/?data=%221000genomes%22&chr=11&pos=113270828 (accessed on 12/27/2023).Ivanova, S.A.; Loonen, A.J.; Pechlivanoglou, P.; Freidin, M.B.; Al Hadithy, A.F.; Rudikov, E.V.; Zhukova, I.A.; Govorin, N.V.; Sorokina, V.A.; Fedorenko, O.Y. et al. NMDA receptor genotypes associated with the vulnerability to develop dyskinesia. Translational Psychiatry 2012, 2:e67. doi:10.1038/tp.2011.66Ivanova, S.A.; Loonen, A.J.; Pechlivanoglou, P.; Freidin, M.B.; Al Hadithy, A.F.; Rudikov, E.V.; Zhukova, I.A.; Govorin, N.V.; Sorokina, V.A.; Fedorenko, O.Y. et al. NMDA receptor genotypes associated with the vulnerability to develop dyskinesia. Translational Psychiatry 2012, 2:e67. doi:10.1038/tp.2011.66Neznanov, N.G. A paradigm shift to treat psychoneurological disorders. Personalized Psychiatry and Neurology. 2021, 1(1):1-2.Neznanov, N.G. A paradigm shift to treat psychoneurological disorders. Personalized Psychiatry and Neurology. 2021, 1(1):1-2.Sapronova, M.R.; Shnaider, N.A. The epidemiological, clinical, and genetic characteristics of Parkinson’s disease (in case of Zheleznogorsk). Neurology, Neuropsychiatry, Psychosomatics. 2014, 6(4):59-64. doi:10.14412/2074-2711-2014-4-59-64Sapronova, M.R.; Shnaider, N.A. The epidemiological, clinical, and genetic characteristics of Parkinson’s disease (in case of Zheleznogorsk). Neurology, Neuropsychiatry, Psychosomatics. 2014, 6(4):59-64. doi:10.14412/2074-2711-2014-4-59-64Sychev, D.A. Genetic features of a patient may influence the efficacy and safety profile of a medicinal product. Safety and Risk of Pharmacotherapy. 2024, 12(2):127-131. doi:10.30895/2312-7821-2024-12-2-127-131Sychev, D.A. Genetic features of a patient may influence the efficacy and safety profile of a medicinal product. Safety and Risk of Pharmacotherapy. 2024, 12(2):127-131. doi:10.30895/2312-7821-2024-12-2-127-131

The authors declare that there are no conflicts of interest present.