{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T05:12:56Z","timestamp":1788671576693,"version":"build-2803163510"},"reference-count":69,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"crossref","award":["075-15-2025-463"],"award-info":[{"award-number":["075-15-2025-463"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Objectives. To identify associations between CYP3A4*22 and CYP3A5*3 genotypes, CYP2D6 phenotype, and the effectiveness and safety of antipsychotics in neurotypically developed boys with conduct disorders. Methods: The study included neurotypically developed boys aged 7\u201312 years who were hospitalized for conduct disorders. All patients were prescribed an antipsychotic. Patient follow-up lasted 14 days. Treatment effectiveness was assessed using a clinical aggression assessment (checklist) and the CGI-S, CGI-I, and CGAS scales. Safety was assessed using the UKU SERS and SAS scales. Patients were examined upon enrollment in the study, on day 5, and on day 14. All patients were genotyped for the CYP3A4*22 (rs35599367, C&gt;T), CYP3A5*3 (rs776746, 6986T&gt;C) CYP2D6*3 (rs35742686), CYP2D6*4 (G1846A, rs3892097), CYP2D6*6 (rs5030655), CYP2D6*10 (C100T, rs1065852), CYP2D6*41 (rs28371725) loci. CYP2D6 metabolism type was determined based on genotyping results, and patients were divided into two subgroups: those with normal metabolism (NM) and those with intermediate or poor metabolism (IM + PM). Results: Patients taking carbamazepine (n = 11) were excluded from the analysis of associations between treatment outcomes and the CYP3A4*22 and CYP3A5*3 polymorphisms. The analysis of associations between treatment outcomes and CYP2D6 metabolism type was conducted in two stages: the overall sample and a subsample of patients who were prescribed risperidone (n = 80). No significant associations were found between carrier status of the CYP3A4*22 and CYP3A5*3 polymorphisms and treatment effectiveness parameters. Analysis of the overall sample did not reveal any significant associations between CYP2D6 metabolism subtypes and the effectiveness parameters of drug therapy. Analysis of patients receiving risperidone revealed one statistically significant association: patients with CYP2D6 IM + PM reported headaches more frequently (16.1% vs. 2%; p = 0.03). Carrier status of the CYP3A4*22 polymorphism was significantly associated with asthenia and lethargy on day 5 (50% vs. 9.4%; p = 0.008). Conclusions: Our study identified only a few significant associations between the CYP3A4*22 polymorphism, CYP2D6 slow metabolism, and patients\u2019 reports of early adverse reactions in a 14-day observation period. Further research is needed to identify pharmacogenetic predictors of the efficacy and safety of antipsychotics in neurotypical children with conduct disorders.<\/jats:p>","DOI":"10.3390\/ph19091401","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T16:07:32Z","timestamp":1788538052000},"page":"1401","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic Polymorphisms CYP3A4*22, CYP3A5*3, and CYP2D6 Predicted Phenotypes Are Not Associated with Antipsychotic Treatment Outcomes in Neurotypical Prepubertal Boys with Conduct Disorders"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2295-7167","authenticated-orcid":false,"given":"Dmitriy V.","family":"Ivashchenko","sequence":"first","affiliation":[{"name":"Federal State Budgetary Research Institution, Russian Research Center of Surgery Named After Academician B.V. Petrovsky, Moscow 119435, Russia"},{"name":"General Psychiatry Department, Scientific-Practical Children\u2019s and Adolescents Mental Health Center n.a. G.E. Sukhareva, Moscow 119334, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Mikhail D.","family":"Che","sequence":"additional","affiliation":[{"name":"General Psychiatry Department, Scientific-Practical Children\u2019s and Adolescents Mental Health Center n.a. G.E. Sukhareva, Moscow 119334, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Farid R.","family":"Aysin","sequence":"additional","affiliation":[{"name":"General Psychiatry Department, Scientific-Practical Children\u2019s and Adolescents Mental Health Center n.a. G.E. Sukhareva, Moscow 119334, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2744-2752","authenticated-orcid":false,"given":"Svetlana N.","family":"Tuchkova","sequence":"additional","affiliation":[{"name":"Federal State Budgetary Research Institution, Russian Research Center of Surgery Named After Academician B.V. Petrovsky, Moscow 119435, Russia"},{"name":"Research Institute for Molecular and Personalized Medicine, Russian Medical Academy of Continuous Professional Education, Moscow 125993, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Ivan N.","family":"Korsakov","sequence":"additional","affiliation":[{"name":"Federal State Budgetary Research Institution, Russian Research Center of Surgery Named After Academician B.V. Petrovsky, Moscow 119435, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Ekaterina I.","family":"Ianavichiute","sequence":"additional","affiliation":[{"name":"General Psychiatry Department, Scientific-Practical Children\u2019s and Adolescents Mental Health Center n.a. G.E. Sukhareva, Moscow 119334, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5384-5902","authenticated-orcid":false,"given":"Mariia A.","family":"Ivashchenko","sequence":"additional","affiliation":[{"name":"Veltischev Research and Clinical Institute for Pediatrics and Pediatric Surgery of the Pirogov Russian National Research Medical University of the Ministry of Health of the Russian Federation, Moscow 117513, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Pavel V.","family":"Shimanov","sequence":"additional","affiliation":[{"name":"General Psychiatry Department, Scientific-Practical Children\u2019s and Adolescents Mental Health Center n.a. G.E. Sukhareva, Moscow 119334, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"given":"Rimma V.","family":"Kondratieva","sequence":"additional","affiliation":[{"name":"General Psychiatry Department, Scientific-Practical Children\u2019s and Adolescents Mental Health Center n.a. G.E. Sukhareva, Moscow 119334, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"given":"Artem V.","family":"Shubin","sequence":"additional","affiliation":[{"name":"General Psychiatry Department, Scientific-Practical Children\u2019s and Adolescents Mental Health Center n.a. G.E. Sukhareva, Moscow 119334, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"given":"Karin B.","family":"Mirzaev","sequence":"additional","affiliation":[{"name":"Federal State Budgetary Research Institution, Russian Research Center of Surgery Named After Academician B.V. Petrovsky, Moscow 119435, Russia"},{"name":"Department of Clinical Pharmacology and Therapeutics, Russian Medical Academy of Continuous Professional Education, Moscow 125993, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Yuriy S.","family":"Shevchenko","sequence":"additional","affiliation":[{"name":"Department of Child Psychiatry and Psychotherapy, Russian Medical Academy of Continuous Professional Education, Moscow 125993, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Dmitry A.","family":"Sychev","sequence":"additional","affiliation":[{"name":"Federal State Budgetary Research Institution, Russian Research Center of Surgery Named After Academician B.V. 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