vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/vjgb-24-74vavilov-4297Research ArticleБИОТЕХНОЛОГИЯ В ПОСТГЕНОМНУЮ ЭРУMEDICAL GENETICSПолиморфные варианты гена рецептора дофамина DRD2 (rs6277, rs1800497) у подростков с проблемным использованием компьютерных видеоигрPolymorphic variants of the dopamine receptor gene DRD2 (rs6277, rs1800497) in adolescents with problematic video game usehttps://orcid.org/0000-0002-1605-7859ТерещенкоС. Ю.TereshchenkoS. Yu.

Красноярск

Krasnoyarsk

https://orcid.org/0000-0002-5006-0429АфоничеваК. В.AfonichevaK. V.

Красноярск

Krasnoyarsk

https://orcid.org/0000-0001-9795-2056МарченкоИ. В.MarchenkoI. V.

Красноярск

Krasnoyarsk

https://orcid.org/0000-0002-6724-1058ШубинаМ. В.ShubinaM. V.

Красноярск

Krasnoyarsk

https://orcid.org/0000-0001-9984-2029СмольниковаМ. В.SmolnikovaM. V.

Красноярск

Krasnoyarsk

smarinv@yandex.ruНаучно-исследовательский институт медицинских проблем Севера – обособленное подразделение Федерального исследовательского центра «Красноярский научный центр Сибирского отделения Российской академии наук»РоссияScientific Research Institute of Medical Problems of the North – a separate division of the Federal Research Center “Krasnoyarsk Science Center” of the Siberian Branch of the Russian Academy of SciencesRussian Federation202409102024286667674Copyright © Терещенко С.Ю., Афоничева К.В., Марченко И.В., Шубина М.В., Смольникова М.В., 20242024Терещенко С.Ю., Афоничева К.В., Марченко И.В., Шубина М.В., Смольникова М.В.Tereshchenko S.Y., Afonicheva K.V., Marchenko I.V., Shubina M.V., Smolnikova M.V.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/4297

Проблемное использование видеоигр как специфическая форма проблемного использования Интернета широко распространено среди подростков и может оказывать негативный эффект на их психическое и соматическое благополучие. Рост зависимости от пользования видеоиграми, как и Интернетом, среди молодого населения делает актуальным изучение факторов подверженности к ним, в том числе генетической составляющей. Существует ряд исследований, посвященных изучению вовлеченности полиморфных вариантов генов системы нейромедиаторов в развитие Интернет-зависимости, результаты которых различаются в разных этнических группах. Ген рецептора дофамина второго типа DRD2 является одним из кандидатных генов подверженности к патологической зависимости от использования видеоигр. Целью работы было исследование полиморфных вариантов гена рецептора дофамина DRD2 (rs6277, rs1800497) у русских подростков с проблемным использованием компьютерных видеоигр. Протестирована выборка из 407 подростков в возрасте 14.1±1.8 года, у 56 (13.8 %) из которых на основании результатов оценки шкалы GASA было выявлено проблемное использование видеоигр. Мальчики в выборке чаще были зависимы от видеоигр, чем девочки (p = 0.041). В результате сравнения частоты аллелей DRD2 rs6277 обнаружена тенденция к большей частоте минорного аллеля T в группе подростков с проблемным использованием видеоигр по сравнению с подростками без проблемного использования видеоигр (0.563 и 0.466 соответственно, p = 0.06). В доминантной модели наследования у подростков с проблемным использованием видеоигр статистически значимо чаще встречалось носительство аллеля T (СТ+ТТ) (p = 0.04, OR 2.14, CI = 1.01–4.53). Носительство аллеля T DRD2 rs6277 ассоциировано с низкой экспрессией дофаминового рецептора D2 и приводит к снижению плотности и аффинности экстрастриарных дофаминовых рецепторов второго типа, что сопряжено в том числе с нарушением социальной коммуникации. Мы полагаем, что наличие генотипов CT и TT rs6277 гена DRD2 может выступать потенциальным фактором риска развития проблемного использования видеоигр у подростков. 

Problematic video games use, as a specific form of problematic Internet use, is widespread among adolescents and can have negative effects on their mental and somatic well-being. An increasing incidence of addictive video gaming, as well as the overuse of the Internet, among the young population makes the current study of susceptibility factors, including the genetic component, relevant. There has been a number of investigations related to the involvement of gene variants of the neurotransmitter system in the development of Internet addiction, with the results being different for various ethnic groups. The dopamine type 2 receptor gene (DRD2) is one of the candidate genes for susceptibility to video game addiction. The aim of the work was to study polymorphic variants of the dopamine receptor gene DRD2 (rs6277, rs1800497) in Russian adolescents with problematic use of computer video games. A sampling of 407 adolescents aged 14.1±1.8 years was tested, of which 56 (13.8 %) were identified as having problems with the pathological use of video games use based on the GASA scale results. Boys in the sample proved to be addicted to video games more than girls (p = 0.041). As a result of comparing the allele frequency of DRD2 (rs6277), a tendency to a higher frequency of the minor allele T was revealed in the group of adolescents with problematic video game use compared with adolescents without problematic video game use (i. e. 0.563 and 0.466, respectively, p = 0.06). When using the dominant inheritance model, it was revealed that adolescents with problematic use of video games were statistically significantly more likely to carry the T (CT+TT) allele (p = 0.04, OR = 2.14, CI = 1.01–4.53). The T allele DRD2 (rs6277) is associated with low expression of the dopamine receptor D2 and leads to decreasing the density and affinity of extrastriatal dopamine type 2 receptors, which is associated with impaired social communication as well. We suggest that the presence of CT and TT genotypes of rs6277 DRD2 may be a potential risk factor for developing problematic video game use in adolescents. 

полиморфизм геновдофаминподросткипроблемное использование компьютерных видеоигригровая зависимостьинтернет-зависимостьgene polymorphismdopamineteenagersproblematic video game usegame addictionInternet addictionReferencesAlcaro A., Brennan A., Conversi D. The SEEKING drive and its fixation: a neuro-psycho-evolutionary approach to the pathology of addiction. Front. Hum. Neurosci. 2021;15:635932. DOI 10.3389/fnhum.2021.635932Alcaro A., Brennan A., Conversi D. The SEEKING drive and its fixation: a neuro-psycho-evolutionary approach to the pathology of addiction. Front. Hum. Neurosci. 2021;15:635932. DOI 10.3389/fnhum.2021.635932Anokhin P.K., Veretinskaya А.G., Davidova Т.V., Shamakina I.Yu. Dopamine D2 agonists in the treatment of experimental alcoholism. Patologicheskaya Fiziologiya i Eksperimental’naya Terapiya = Pathological Physiology and Experimental Therapy. 2019;63(1):33- 39. DOI 10.25557/0031-2991.2019.01.33-39 (in Russian)Anokhin P.K., Veretinskaya А.G., Davidova Т.V., Shamakina I.Yu. Dopamine D2 agonists in the treatment of experimental alcoholism. Patologicheskaya Fiziologiya i Eksperimental’naya Terapiya = Pathological Physiology and Experimental Therapy. 2019;63(1):33- 39. DOI 10.25557/0031-2991.2019.01.33-39 (in Russian)Arnsten A.F.T., Wang M., Paspalas C.D. Dopamine’s actions in primate prefrontal cortex: challenges for treating cognitive disorders. Pharmacol. Rev. 2015;67(3):681-696. DOI 10.1124/pr.115.010512Arnsten A.F.T., Wang M., Paspalas C.D. Dopamine’s actions in primate prefrontal cortex: challenges for treating cognitive disorders. Pharmacol. Rev. 2015;67(3):681-696. DOI 10.1124/pr.115.010512Bhaskar L.V.K.S., Kumar S.A. Polymorphisms in genes encoding dopamine signalling pathway and risk of alcohol dependence: a systematic review. Acta Neuropsychiatrica. 2014;26(2):69-80. DOI 10.1017/neu.2013.27Bhaskar L.V.K.S., Kumar S.A. Polymorphisms in genes encoding dopamine signalling pathway and risk of alcohol dependence: a systematic review. Acta Neuropsychiatrica. 2014;26(2):69-80. DOI 10.1017/neu.2013.27Casey B.J., Jones R.M., Hare T.A. The adolescent brain. Ann. N.Y. Acad. Sci. 2008;1124:111-126. DOI 10.1196/annals.1440.010Casey B.J., Jones R.M., Hare T.A. The adolescent brain. Ann. N.Y. Acad. Sci. 2008;1124:111-126. DOI 10.1196/annals.1440.010Colzato L.S., van den Wildenberg W.P.M., Van der Does A.J.W., Hommel B. Genetic markers of striatal dopamine predict individual differences in dysfunctional, but not functional impulsivity. Neuroscience. 2010;170(3):782-788. DOI 10.1016/j.neuroscience.2010.07.050Colzato L.S., van den Wildenberg W.P.M., Van der Does A.J.W., Hommel B. Genetic markers of striatal dopamine predict individual differences in dysfunctional, but not functional impulsivity. Neuroscience. 2010;170(3):782-788. DOI 10.1016/j.neuroscience.2010.07.050de Ridder D.T.D., Lensvelt-Mulders G., Finkenauer C., Stok F.M., Baumeister R.F. Taking stock of self-control: a meta-analysis of how trait self-control relates to a wide range of behaviors. Pers. Soc. Psychol. Rev. 2012;16(1):76-99. DOI 10.1177/1088868311418749de Ridder D.T.D., Lensvelt-Mulders G., Finkenauer C., Stok F.M., Baumeister R.F. Taking stock of self-control: a meta-analysis of how trait self-control relates to a wide range of behaviors. Pers. Soc. Psychol. Rev. 2012;16(1):76-99. DOI 10.1177/1088868311418749Della Torre O.H., Paes L.A., Henriques T.B., de Mello M.P., Celeri E.H.R.V., Dalgalarrondo P., Guerra-Júnior G., Santos-Júnior A.D. Dopamine D2 receptor gene polymorphisms and externalizing behaviors in children and adolescents. BMC Med. Genet. 2018;19(1): 65. DOI 10.1186/s12881-018-0586-9Della Torre O.H., Paes L.A., Henriques T.B., de Mello M.P., Celeri E.H.R.V., Dalgalarrondo P., Guerra-Júnior G., Santos-Júnior A.D. Dopamine D2 receptor gene polymorphisms and externalizing behaviors in children and adolescents. BMC Med. Genet. 2018;19(1): 65. DOI 10.1186/s12881-018-0586-9Deryakulu D., Ursavaş Ö.F. Genetic and environmental influences on problematic Internet use: a twin study. Comput. Hum. Behav. 2014; 39:331-338. DOI 10.1016/j.chb.2014.07.038Deryakulu D., Ursavaş Ö.F. Genetic and environmental influences on problematic Internet use: a twin study. Comput. Hum. Behav. 2014; 39:331-338. DOI 10.1016/j.chb.2014.07.038Dichter G.S., Damiano C.A., Allen J.A. Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings. J. Neurodev. Disord. 2012;4(1):19. DOI 10.1186/1866-1955-4-19Dichter G.S., Damiano C.A., Allen J.A. Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings. J. Neurodev. Disord. 2012;4(1):19. DOI 10.1186/1866-1955-4-19Fineberg N.A., Menchón J.M., Hall N., Dell’Osso B., Brand M., Potenza M.N., Chamberlain S.R., Cirnigliaro G., Lochner C., Billieux J., … Cataldo I., Riva G.M., Yücel M., Flayelle M., Hall T., Griffiths M., Zohar J. Advances in problematic usage of the internet research – a narrative review by experts from the European network for problematic usage of the internet. Compr. Psychiatry. 2022;118: 152346. DOI 10.1016/j.comppsych.2022.152346Fineberg N.A., Menchón J.M., Hall N., Dell’Osso B., Brand M., Potenza M.N., Chamberlain S.R., Cirnigliaro G., Lochner C., Billieux J., … Cataldo I., Riva G.M., Yücel M., Flayelle M., Hall T., Griffiths M., Zohar J. Advances in problematic usage of the internet research – a narrative review by experts from the European network for problematic usage of the internet. Compr. Psychiatry. 2022;118: 152346. DOI 10.1016/j.comppsych.2022.152346Ford C.P. The role of D2-autoreceptors in regulating dopamine neuron activity and transmission. Neuroscience. 2014;282:13-22. DOI 10.1016/j.neuroscience.2014.01.025Ford C.P. The role of D2-autoreceptors in regulating dopamine neuron activity and transmission. Neuroscience. 2014;282:13-22. DOI 10.1016/j.neuroscience.2014.01.025Gafarov V.V., Gromova E.A., Panov D.O., Maximov V.N., Gagulin I.V., Gafarova A.V. Association of DRD2/ANKK1 Taq1A polymorphism with depression in an open 45–64 year-old male population (international epidemiological HAPIEE and WHO MONICA programs). Nevrologiya, Neiropsikhiatriya, Psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2019;11(2):37-41. DOI 10.14412/ 2074-2711-2019-2-37-41Gafarov V.V., Gromova E.A., Panov D.O., Maximov V.N., Gagulin I.V., Gafarova A.V. Association of DRD2/ANKK1 Taq1A polymorphism with depression in an open 45–64 year-old male population (international epidemiological HAPIEE and WHO MONICA programs). Nevrologiya, Neiropsikhiatriya, Psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2019;11(2):37-41. DOI 10.14412/ 2074-2711-2019-2-37-41Gao X., Wang Y., Lang M., Yuan L., Reece A.S., Wang W. Contribution of genetic polymorphisms and haplotypes in DRD2, BDNF, and opioid receptors to heroin dependence and endophenotypes among the Han Chinese. OMICS. 2017;21(7):404-412. DOI 10.1089/omi.2017.0057Gao X., Wang Y., Lang M., Yuan L., Reece A.S., Wang W. Contribution of genetic polymorphisms and haplotypes in DRD2, BDNF, and opioid receptors to heroin dependence and endophenotypes among the Han Chinese. OMICS. 2017;21(7):404-412. DOI 10.1089/omi.2017.0057Griffiths M.D., Kuss D.J., King D.L. Video game addiction: past, present and future. Curr. Psychiatry Rev. 2012;8(4):308-318. DOI 10.2174/157340012803520414Griffiths M.D., Kuss D.J., King D.L. Video game addiction: past, present and future. Curr. Psychiatry Rev. 2012;8(4):308-318. DOI 10.2174/157340012803520414Hahn E., Reuter M., Spinath F.M., Montag C. Internet addiction and its facets: the role of genetics and the relation to self-directedness. Addict. Behav. 2017;65:137-146. DOI 10.1016/j.addbeh.2016.10.018Hahn E., Reuter M., Spinath F.M., Montag C. Internet addiction and its facets: the role of genetics and the relation to self-directedness. Addict. Behav. 2017;65:137-146. DOI 10.1016/j.addbeh.2016.10.018Han D.H., Lee Y.S., Yang K.C., Kim E.Y., Lyoo I.K., Renshaw P.F. Dopamine genes and reward dependence in adolescents with excessive internet video game play. J. Addict. Med. 2007;1(3):133-138. DOI 10.1097/ADM.0b013e31811f465fHan D.H., Lee Y.S., Yang K.C., Kim E.Y., Lyoo I.K., Renshaw P.F. Dopamine genes and reward dependence in adolescents with excessive internet video game play. J. Addict. Med. 2007;1(3):133-138. DOI 10.1097/ADM.0b013e31811f465fHänninen K., Katila H., Kampman O., Anttila S., Illi A., Rontu R., Mattila K.M., Hietala J., Hurme M., Leinonen E., Lehtimäki T. Association between the C957T polymorphism of the dopamine D2 receptor gene and schizophrenia. Neurosci. Lett. 2006;407(3):195-198. DOI 10.1016/j.neulet.2006.08.041Hänninen K., Katila H., Kampman O., Anttila S., Illi A., Rontu R., Mattila K.M., Hietala J., Hurme M., Leinonen E., Lehtimäki T. Association between the C957T polymorphism of the dopamine D2 receptor gene and schizophrenia. Neurosci. Lett. 2006;407(3):195-198. DOI 10.1016/j.neulet.2006.08.041He J., Crews F.T. Neurogenesis decreases during brain maturation from adolescence to adulthood. Pharmacol. Biochem. Behav. 2007;86(2): 327-333. DOI 10.1016/j.pbb.2006.11.003He J., Crews F.T. Neurogenesis decreases during brain maturation from adolescence to adulthood. Pharmacol. Biochem. Behav. 2007;86(2): 327-333. DOI 10.1016/j.pbb.2006.11.003Hill S.Y., Hoffman E.K., Zezza N., Thalamuthu A., Weeks D.E., Matthews A.G., Mukhopadhyay I. Dopaminergic mutations: within-family association and linkage in multiplex alcohol dependence families. Am. J. Med. Genet. B Neuropsychiatr. Genet. 2008;147B(4): 517-526. DOI 10.1002/ajmg.b.30630Hill S.Y., Hoffman E.K., Zezza N., Thalamuthu A., Weeks D.E., Matthews A.G., Mukhopadhyay I. Dopaminergic mutations: within-family association and linkage in multiplex alcohol dependence families. Am. J. Med. Genet. B Neuropsychiatr. Genet. 2008;147B(4): 517-526. DOI 10.1002/ajmg.b.30630Hill S.Y., Lichenstein S., Wang S., Carter H., McDermott M. Caudate volume in offspring at ultra high risk for alcohol dependence: COMT Val158Met, DRD2, externalizing disorders, and working memory. Adv. J. Mol. Imaging. 2013;3(4):43-54. DOI 10.4236/ami.2013.34007Hill S.Y., Lichenstein S., Wang S., Carter H., McDermott M. Caudate volume in offspring at ultra high risk for alcohol dependence: COMT Val158Met, DRD2, externalizing disorders, and working memory. Adv. J. Mol. Imaging. 2013;3(4):43-54. DOI 10.4236/ami.2013.34007Hirvonen M.M., Lumme V., Hirvonen J., Pesonen U., Någren K., Vahlberg T., Scheinin H., Hietala J. C957T polymorphism of the human dopamine D2 receptor gene predicts extrastriatal dopamine receptor availability in vivo. Prog. Neuropsychopharmacol. Biol. Psychiatry. 2009;33(4):630-636. DOI 10.1016/j.pnpbp.2009.02.021Hirvonen M.M., Lumme V., Hirvonen J., Pesonen U., Någren K., Vahlberg T., Scheinin H., Hietala J. C957T polymorphism of the human dopamine D2 receptor gene predicts extrastriatal dopamine receptor availability in vivo. Prog. Neuropsychopharmacol. Biol. Psychiatry. 2009;33(4):630-636. DOI 10.1016/j.pnpbp.2009.02.021Ioannidis K., Hook R., Goudriaan A.E., Vlies S., Fineberg N.A., Grant J.E., Chamberlain S.R. Cognitive deficits in problematic internet use: meta-analysis of 40 studies. Br. J. Psychiatry. 2019;215(5): 639-646. DOI 10.1192/bjp.2019.3Ioannidis K., Hook R., Goudriaan A.E., Vlies S., Fineberg N.A., Grant J.E., Chamberlain S.R. Cognitive deficits in problematic internet use: meta-analysis of 40 studies. Br. J. Psychiatry. 2019;215(5): 639-646. DOI 10.1192/bjp.2019.3Kim E., Lee D., Do K., Kim J. Interaction effects of DRD2 genetic polymorphism and interpersonal stress on problematic gaming in college students. Genes (Basel). 2022;13(3):449. DOI 10.3390/genes13030449Kim E., Lee D., Do K., Kim J. Interaction effects of DRD2 genetic polymorphism and interpersonal stress on problematic gaming in college students. Genes (Basel). 2022;13(3):449. DOI 10.3390/genes13030449Klaus K., Vaht M., Pennington K., Harro J. Interactive effects of DRD2 rs6277 polymorphism, environment and sex on impulsivity in a population-representative study. Behav. Brain Res. 2021;403:113131. DOI 10.1016/j.bbr.2021.113131Klaus K., Vaht M., Pennington K., Harro J. Interactive effects of DRD2 rs6277 polymorphism, environment and sex on impulsivity in a population-representative study. Behav. Brain Res. 2021;403:113131. DOI 10.1016/j.bbr.2021.113131Klein T.A., Neumann J., Reuter M., Hennig J., von Cramon D.Y., Ullsperger M. Genetically determined differences in learning from errors. Science. 2007;318(5856):1642-1645. DOI 10.1126/science.1145044Klein T.A., Neumann J., Reuter M., Hennig J., von Cramon D.Y., Ullsperger M. Genetically determined differences in learning from errors. Science. 2007;318(5856):1642-1645. DOI 10.1126/science.1145044Kolotilova O.I., Koreniuk I.I., Khusainov D.R., Cheretaev I.V. Dopaminergic brain system. Vestnik Bryanskogo Gosudarstvennogo Universiteta = The Bryansk State University Herald. 2014;4:97-106 (in Russian)Kolotilova O.I., Koreniuk I.I., Khusainov D.R., Cheretaev I.V. Dopaminergic brain system. Vestnik Bryanskogo Gosudarstvennogo Universiteta = The Bryansk State University Herald. 2014;4:97-106 (in Russian)Kushnarev A.P. The study of polymorphism of the dopamine receptor type 4 (DRD4) and dopamine transporter (DAT) genes in individuals with antisocial behavior and representatives of extreme professions. Meditsina. Sotsiologiya. Filosofiya. Prikladnyye Issledovaniya = Medicine. Sociology. Philosophy. Applied Research. 2022;3:40-47 (in Russian)Kushnarev A.P. The study of polymorphism of the dopamine receptor type 4 (DRD4) and dopamine transporter (DAT) genes in individuals with antisocial behavior and representatives of extreme professions. Meditsina. Sotsiologiya. Filosofiya. Prikladnyye Issledovaniya = Medicine. Sociology. Philosophy. Applied Research. 2022;3:40-47 (in Russian)Lemmens J.S., Valkenburg P.M., Peter J. Development and validation of a game addiction scale for adolescents. Media Psychology. 2009;12(1):77-95. DOI 10.1080/15213260802669458Lemmens J.S., Valkenburg P.M., Peter J. Development and validation of a game addiction scale for adolescents. Media Psychology. 2009;12(1):77-95. DOI 10.1080/15213260802669458Li M., Chen J., Li N., Li X. A twin study of problematic internet use: its heritability and genetic association with effortful control. Twin Res. Hum. Genet. 2014;17(4):279-287. DOI 10.1017/thg.2014.32Li M., Chen J., Li N., Li X. A twin study of problematic internet use: its heritability and genetic association with effortful control. Twin Res. Hum. Genet. 2014;17(4):279-287. DOI 10.1017/thg.2014.32Li S., Ren P., Chiu M.M., Wang C., Lei H. The relationship between self-control and internet addiction among students: a meta-analysis. Front. Psychol. 2021;12:735755. DOI 10.3389/fpsyg.2021.735755Li S., Ren P., Chiu M.M., Wang C., Lei H. The relationship between self-control and internet addiction among students: a meta-analysis. Front. Psychol. 2021;12:735755. DOI 10.3389/fpsyg.2021.735755Li W., Zhang W., Xiao L., Nie J. The association of Internet addiction symptoms with impulsiveness, loneliness, novelty seeking and behavioral inhibition system among adults with attention-deficit/ hyperactivity disorder (ADHD). Psychiatry Res. 2016;243:357-364. DOI 10.1016/j.psychres.2016.02.020Li W., Zhang W., Xiao L., Nie J. The association of Internet addiction symptoms with impulsiveness, loneliness, novelty seeking and behavioral inhibition system among adults with attention-deficit/ hyperactivity disorder (ADHD). Psychiatry Res. 2016;243:357-364. DOI 10.1016/j.psychres.2016.02.020Liu L., Fan D., Ding N., Hu Y., Cai G., Wang L., Xin L., Xia Q., Li X., Xu S., Xu J., Yang X., Zou Y., Pan F. The relationship between DRD2 gene polymorphisms (C957T and C939T) and schizophrenia: a meta-analysis. Neurosci. Lett. 2014;583:43-48. DOI 10.1016/j.neulet.2014.09.024Liu L., Fan D., Ding N., Hu Y., Cai G., Wang L., Xin L., Xia Q., Li X., Xu S., Xu J., Yang X., Zou Y., Pan F. The relationship between DRD2 gene polymorphisms (C957T and C939T) and schizophrenia: a meta-analysis. Neurosci. Lett. 2014;583:43-48. DOI 10.1016/j.neulet.2014.09.024Long E.C., Verhulst B., Neale M.C., Lind P.A., Hickie I.B., Martin N.G., Gillespie N.A. The genetic and environmental contributions to Internet use and associations with psychopathology: a twin study. Twin Res. Hum. Genet. 2016;19(1):1-9. DOI 10.1017/thg.2015.91Long E.C., Verhulst B., Neale M.C., Lind P.A., Hickie I.B., Martin N.G., Gillespie N.A. The genetic and environmental contributions to Internet use and associations with psychopathology: a twin study. Twin Res. Hum. Genet. 2016;19(1):1-9. DOI 10.1017/thg.2015.91Machulska A., Zlomuzica A., Rinck M., Assion H.-J., Margraf J. Approach bias modification in inpatient psychiatric smokers. J. Psychiatric Res. 2016;76:44-51. DOI 10.1016/j.jpsychires.2015.11.015Machulska A., Zlomuzica A., Rinck M., Assion H.-J., Margraf J. Approach bias modification in inpatient psychiatric smokers. J. Psychiatric Res. 2016;76:44-51. DOI 10.1016/j.jpsychires.2015.11.015Magistrelli L., Ferrari M., Furgiuele A., Milner A.V., Contaldi E., Comi C., Cosentino M., Marino F. Polymorphisms of dopamine receptor genes and Parkinson’s disease: clinical relevance and future perspectives. Int. J. Mol. Sci. 2021;22(7):3781. DOI 10.3390/ijms22073781Magistrelli L., Ferrari M., Furgiuele A., Milner A.V., Contaldi E., Comi C., Cosentino M., Marino F. Polymorphisms of dopamine receptor genes and Parkinson’s disease: clinical relevance and future perspectives. Int. J. Mol. Sci. 2021;22(7):3781. DOI 10.3390/ijms22073781Männikkö N., Ruotsalainen H., Miettunen J., Pontes H.M., Kääriäinen M. Problematic gaming behaviour and health-related outcomes: a systematic review and meta-analysis. J. Health. Psychol. 2020; 25(1):67-81. DOI 10.1177/1359105317740414Männikkö N., Ruotsalainen H., Miettunen J., Pontes H.M., Kääriäinen M. Problematic gaming behaviour and health-related outcomes: a systematic review and meta-analysis. J. Health. Psychol. 2020; 25(1):67-81. DOI 10.1177/1359105317740414Matthys W., Vanderschuren L.J.M.J., Schutter D.J.L.G. The neurobiology of oppositional defiant disorder and conduct disorder: altered functioning in three mental domains. Dev. Psychopathol. 2013; 25(1):193-207. DOI 10.1017/S0954579412000272Matthys W., Vanderschuren L.J.M.J., Schutter D.J.L.G. The neurobiology of oppositional defiant disorder and conduct disorder: altered functioning in three mental domains. Dev. Psychopathol. 2013; 25(1):193-207. DOI 10.1017/S0954579412000272Mihara S., Higuchi S. Cross-sectional and longitudinal epidemiological studies of Internet gaming disorder: a systematic review of the literature. Psychiatry Clin. Neurosci. 2017;71(7):425-444. DOI 10.1111/pcn.12532Mihara S., Higuchi S. Cross-sectional and longitudinal epidemiological studies of Internet gaming disorder: a systematic review of the literature. Psychiatry Clin. Neurosci. 2017;71(7):425-444. DOI 10.1111/pcn.12532Murayama C., Iwabuchi T., Kato Y., Yokokura M., Harada T., Goto T., Tamayama T., Kameno Y., Wakuda T., Kuwabara H., Senju A., Nishizawa S., Ouchi Y., Yamasue H. Extrastriatal dopamine D2/3 receptor binding, functional connectivity, and autism socio-communicational deficits: a PET and fMRI study. Mol. Psychiatry. 2022; 27(4):2106-2113. DOI 10.1038/s41380-022-01464-3Murayama C., Iwabuchi T., Kato Y., Yokokura M., Harada T., Goto T., Tamayama T., Kameno Y., Wakuda T., Kuwabara H., Senju A., Nishizawa S., Ouchi Y., Yamasue H. Extrastriatal dopamine D2/3 receptor binding, functional connectivity, and autism socio-communicational deficits: a PET and fMRI study. Mol. Psychiatry. 2022; 27(4):2106-2113. DOI 10.1038/s41380-022-01464-3Paik S.-H., Choi M.R., Kwak S.M., Bang S.H., Chun J.-W., Kim J.-Y., Choi J., Cho H., Jeong J.-E., Kim D.-J. An association study of Taq1A ANKK1 and C957T and –141C DRD2 polymorphisms in adults with internet gaming disorder: a pilot study. Ann. Gen. Psychiatry. 2017;16:45. DOI 10.1186/s12991-017-0168-9Paik S.-H., Choi M.R., Kwak S.M., Bang S.H., Chun J.-W., Kim J.-Y., Choi J., Cho H., Jeong J.-E., Kim D.-J. An association study of Taq1A ANKK1 and C957T and –141C DRD2 polymorphisms in adults with internet gaming disorder: a pilot study. Ann. Gen. Psychiatry. 2017;16:45. DOI 10.1186/s12991-017-0168-9Paulus F.W., Ohmann S., von Gontard A., Popow C. Internet gaming disorder in children and adolescents: a systematic review. Dev. Med. Child Neurol. 2018;60(7):645-659. DOI 10.1111/dmcn.13754Paulus F.W., Ohmann S., von Gontard A., Popow C. Internet gaming disorder in children and adolescents: a systematic review. Dev. Med. Child Neurol. 2018;60(7):645-659. DOI 10.1111/dmcn.13754Picci G., Fishbein D.H., VanMeter J.W., Rose E.J. Effects of OPRM1 and DRD2 on brain structure in drug-naïve adolescents: genetic and neural vulnerabilities to substance use. Psychopharmacology (Berl.). 2022;239(1):141-152. DOI 10.1007/s00213-021-06030-3Picci G., Fishbein D.H., VanMeter J.W., Rose E.J. Effects of OPRM1 and DRD2 on brain structure in drug-naïve adolescents: genetic and neural vulnerabilities to substance use. Psychopharmacology (Berl.). 2022;239(1):141-152. DOI 10.1007/s00213-021-06030-3Pohjalainen T., Rinne J.O., Någren K., Lehikoinen P., Anttila K., Syvälahti E.K., Hietala J. The A1 allele of the human D2 dopamine receptor gene predicts low D2 receptor availability in healthy volunteers. Mol. Psychiatry. 1998;3(3):256-260. DOI 10.1038/sj.mp.4000350Pohjalainen T., Rinne J.O., Någren K., Lehikoinen P., Anttila K., Syvälahti E.K., Hietala J. The A1 allele of the human D2 dopamine receptor gene predicts low D2 receptor availability in healthy volunteers. Mol. Psychiatry. 1998;3(3):256-260. DOI 10.1038/sj.mp.4000350Richter A., Barman A., Wüstenberg T., Soch J., Schanze D., Deibele A., Behnisch G., Assmann A., Klein M., Zenker M., Seidenbecher C., Schott B.H. Behavioral and neural manifestations of reward memory in carriers of low-expressing versus high-expressing genetic variants of the dopamine D2 receptor. Front. Psychol. 2017;8:654. DOI 10.3389/fpsyg.2017.00654Richter A., Barman A., Wüstenberg T., Soch J., Schanze D., Deibele A., Behnisch G., Assmann A., Klein M., Zenker M., Seidenbecher C., Schott B.H. Behavioral and neural manifestations of reward memory in carriers of low-expressing versus high-expressing genetic variants of the dopamine D2 receptor. Front. Psychol. 2017;8:654. DOI 10.3389/fpsyg.2017.00654Rył A., Tomska N., Jakubowska A., Ogrodniczak A., Palma J., Rotter I. Genetic aspects of problematic and risky Internet use in young men – analysis of ANKK1, DRD2 and NTRK3 gene polymorphism. Genes (Basel). 2024;15(2):169. DOI 10.3390/genes15020169Rył A., Tomska N., Jakubowska A., Ogrodniczak A., Palma J., Rotter I. Genetic aspects of problematic and risky Internet use in young men – analysis of ANKK1, DRD2 and NTRK3 gene polymorphism. Genes (Basel). 2024;15(2):169. DOI 10.3390/genes15020169Smith C.T., Dang L.C., Buckholtz J.W., Tetreault A.M., Cowan R.L., Kessler R.M., Zald D.H. The impact of common dopamine D2 receptor gene polymorphisms on D2/3 receptor availability: C957T as a key determinant in putamen and ventral striatum. Transl. Psychiatry. 2017;7(4):e1091-e1091. DOI 10.1038/tp.2017.45Smith C.T., Dang L.C., Buckholtz J.W., Tetreault A.M., Cowan R.L., Kessler R.M., Zald D.H. The impact of common dopamine D2 receptor gene polymorphisms on D2/3 receptor availability: C957T as a key determinant in putamen and ventral striatum. Transl. Psychiatry. 2017;7(4):e1091-e1091. DOI 10.1038/tp.2017.45Sussman C.J., Harper J.M., Stahl J.L., Weigle P. Internet and video game addictions: diagnosis, epidemiology, and neurobiology. Child Adolesc. Psychiatr. Clin. N. Am. 2018;27(2):307-326. DOI 10.1016/j.chc.2017.11.015Sussman C.J., Harper J.M., Stahl J.L., Weigle P. Internet and video game addictions: diagnosis, epidemiology, and neurobiology. Child Adolesc. Psychiatr. Clin. N. Am. 2018;27(2):307-326. DOI 10.1016/j.chc.2017.11.015Takahashi H., Higuchi M., Suhara T. The role of extrastriatal dopamine D2 receptors in schizophrenia. Biol. Psychiatry. 2006;59(10):919- 928. DOI 10.1016/j.biopsych.2006.01.022Takahashi H., Higuchi M., Suhara T. The role of extrastriatal dopamine D2 receptors in schizophrenia. Biol. Psychiatry. 2006;59(10):919- 928. DOI 10.1016/j.biopsych.2006.01.022Tereshchenko S., Kasparov E., Semenova N., Shubina M., Gorbacheva N., Novitckii I., Moskalenko O., Lapteva L. Generalized and specific problematic internet use in Central Siberia adolescents: a school-based study of prevalence, age-sex depending content structure, and comorbidity with psychosocial problems. Int. J. Environ. Res. Public Health. 2022;19(13):7593. DOI 10.3390/ijerph 19137593Tereshchenko S., Kasparov E., Semenova N., Shubina M., Gorbacheva N., Novitckii I., Moskalenko O., Lapteva L. Generalized and specific problematic internet use in Central Siberia adolescents: a school-based study of prevalence, age-sex depending content structure, and comorbidity with psychosocial problems. Int. J. Environ. Res. Public Health. 2022;19(13):7593. DOI 10.3390/ijerph 19137593Vink J.M., van Beijsterveldt T.C.E.M., Huppertz C., Bartels M., Boomsma D.I. Heritability of compulsive Internet use in adolescents. Addict. Biol. 2016;21(2):460-468. DOI 10.1111/adb.12218Vink J.M., van Beijsterveldt T.C.E.M., Huppertz C., Bartels M., Boomsma D.I. Heritability of compulsive Internet use in adolescents. Addict. Biol. 2016;21(2):460-468. DOI 10.1111/adb.12218Volkow N.D., Wang G.J., Fowler J.S., Logan J., Hitzemann R., Ding Y.S., Pappas N., Shea C., Piscani K. Decreases in dopamine receptors but not in dopamine transporters in alcoholics. Alcohol Clin. Exp. Res. 1996;20(9):1594-1598. DOI 10.1111/j.1530- 0277.1996.tb05936.xVolkow N.D., Wang G.J., Fowler J.S., Logan J., Hitzemann R., Ding Y.S., Pappas N., Shea C., Piscani K. Decreases in dopamine receptors but not in dopamine transporters in alcoholics. Alcohol Clin. Exp. Res. 1996;20(9):1594-1598. DOI 10.1111/j.1530- 0277.1996.tb05936.xWang B.-Q., Yao N.-Q., Zhou X., Liu J., Lv Z.-T. The association between attention deficit/hyperactivity disorder and internet addiction: a systematic review and meta-analysis. BMC Psychiatry. 2017; 17(1):260. DOI 10.1186/s12888-017-1408-xWang B.-Q., Yao N.-Q., Zhou X., Liu J., Lv Z.-T. The association between attention deficit/hyperactivity disorder and internet addiction: a systematic review and meta-analysis. BMC Psychiatry. 2017; 17(1):260. DOI 10.1186/s12888-017-1408-xWeinstein A., Lejoyeux M. Neurobiological mechanisms underlying internet gaming disorder. Dialogues Clin. Neurosci. 2020;22(2): 113-126. DOI 10.31887/DCNS.2020.22.2/aweinsteinWeinstein A., Lejoyeux M. Neurobiological mechanisms underlying internet gaming disorder. Dialogues Clin. Neurosci. 2020;22(2): 113-126. DOI 10.31887/DCNS.2020.22.2/aweinsteinWerling A.M., Grünblatt E. A review of the genetic basis of problematic Internet use. Curr. Opin. Behav. Sci. 2022;46:101149. DOI 10.1016/j.cobeha.2022.101149Werling A.M., Grünblatt E. A review of the genetic basis of problematic Internet use. Curr. Opin. Behav. Sci. 2022;46:101149. DOI 10.1016/j.cobeha.2022.101149Yu Y., Mo P.K.-H., Zhang J., Li J., Lau J.T.-F. Impulsivity, self-control, interpersonal influences, and maladaptive cognitions as factors of internet gaming disorder among adolescents in China: cross-sectional mediation study. J. Med. Internet. Res. 2021;23(10):e26810. DOI 10.2196/26810Yu Y., Mo P.K.-H., Zhang J., Li J., Lau J.T.-F. Impulsivity, self-control, interpersonal influences, and maladaptive cognitions as factors of internet gaming disorder among adolescents in China: cross-sectional mediation study. J. Med. Internet. Res. 2021;23(10):e26810. DOI 10.2196/26810Zhang M., Gao X., Yang Z., Wen M., Huang H., Zheng R., Wang W., Wei Y., Cheng J., Han S., Zhang Y. Shared gray matter alterations in subtypes of addiction: a voxel-wise meta-analysis. Psychopharmacology (Berl.). 2021;238(9):2365-2379. DOI 10.1007/s00213- 021-05920-wZhang M., Gao X., Yang Z., Wen M., Huang H., Zheng R., Wang W., Wei Y., Cheng J., Han S., Zhang Y. Shared gray matter alterations in subtypes of addiction: a voxel-wise meta-analysis. Psychopharmacology (Berl.). 2021;238(9):2365-2379. DOI 10.1007/s00213- 021-05920-w

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