{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T21:12:20Z","timestamp":1762377140326,"version":"build-2065373602"},"reference-count":79,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,4,8]],"date-time":"2022-04-08T00:00:00Z","timestamp":1649376000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Minister of Science and Higher Education under the name &quot;Regional Initiative of Excellence&quot; in 2019-2022","award":["002\/RID\/2018\/19"],"award-info":[{"award-number":["002\/RID\/2018\/19"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Fetal alcohol spectrum disorders (FASD) in a course of high prenatal alcohol exposure (hPAE) are among the most common causes of developmental disorders. The main reason for pharmacological treatment of FASD children is attention deficit hyperactivity disorder (ADHD), and methylphenidate (MPH) is the drug of choice. The aim of the study was to assess whether children born of hPAE with ADHD, with or without morphological FASD, differ in terms of catechol-O-methyltransferase (COMT) and dopamine receptor D2 (DRD2) gene polymorphisms, and if genetic predisposition affects response and safety of MPH treatment. The polymorphisms of COMT (rs4680) and DRD2 (rs1076560, rs1800497) were analyzed in DNA samples. A borderline significance was found for the correlation between MPH side effects and the G allele of COMT (rs4680) (p = 0.04994) in all ADHD children. No effect of COMT (rs4680) and DRD2 (rs1076560, rs1800497) polymorphisms and the treatment efficacy was observed. The analyzed DRD2 and COMT gene polymorphisms seem to play no role in MPH efficacy in ADHD children with hPAE, while low-activity COMT (Met158) variant carriers may be more intolerant to MPH. The MPH treatment is effective in ADHD independent of FASD, although the ADHD-FASD variant requires higher doses to be successful. These results may help in optimization and individualization in child psychiatry.<\/jats:p>","DOI":"10.3390\/ijerph19084479","type":"journal-article","created":{"date-parts":[[2022,4,8]],"date-time":"2022-04-08T12:11:14Z","timestamp":1649419874000},"page":"4479","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Influence of COMT (rs4680) and DRD2 (rs1076560, rs1800497) Gene Polymorphisms on Safety and Efficacy of Methylphenidate Treatment in Children with Fetal Alcohol Spectrum Disorders"],"prefix":"10.3390","volume":"19","author":[{"given":"Ma\u0142gorzata","family":"\u015amiarowska","sequence":"first","affiliation":[{"name":"Department of Pharmacokinetics and Therapeutic Drug Monitoring, Pomeranian Medical University, Aleja Powstanc\u03ccw Wielkopolskich 72 St., 70-111 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bogus\u0142aw","family":"Brzuchalski","sequence":"additional","affiliation":[{"name":"Department of Pharmacokinetics and Therapeutic Drug Monitoring, Pomeranian Medical University, Aleja Powstanc\u03ccw Wielkopolskich 72 St., 70-111 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8890-8616","authenticated-orcid":false,"given":"El\u017cbieta","family":"Grzywacz","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, Pomeranian Medical University, Aleja Powstanc\u03ccw Wielkopolskich 72 St., 70-111 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8393-9627","authenticated-orcid":false,"given":"Damian","family":"Malinowski","sequence":"additional","affiliation":[{"name":"Department of Pharmacokinetics and Therapeutic Drug Monitoring, Pomeranian Medical University, Aleja Powstanc\u03ccw Wielkopolskich 72 St., 70-111 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Machoy-Mokrzy\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, Pomeranian Medical University, Aleja Powstanc\u03ccw Wielkopolskich 72 St., 70-111 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1606-7918","authenticated-orcid":false,"given":"Anna","family":"Pierzchli\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Pharmacokinetics and Therapeutic Drug Monitoring, Pomeranian Medical University, Aleja Powstanc\u03ccw Wielkopolskich 72 St., 70-111 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monika","family":"Bia\u0142ecka","sequence":"additional","affiliation":[{"name":"Department of Pharmacokinetics and Therapeutic Drug Monitoring, Pomeranian Medical University, Aleja Powstanc\u03ccw Wielkopolskich 72 St., 70-111 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1080\/10508422.2014.946031","article-title":"Why Ask Why? Logical Fallacies in the Diagnosis of Fetal Alcohol Spectrum Disorder","volume":"25","author":"Price","year":"2014","journal-title":"Ethic-Behav."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1089\/zeb.2016.1270","article-title":"Fishing for Fetal Alcohol Spectrum Disorders: Zebrafish as a Model for Ethanol Teratogenesis","volume":"13","author":"Fernandes","year":"2016","journal-title":"Zebrafish"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Sidik, A., Dixon, G., Buckley, D.M., Kirby, H.G., Sun, S., and Eberhart, J.K. (2021). Exposure to ethanol leads to midfacial hypoplasia in a zebrafish model of FASD via indirect interactions with the Shh pathway. BMC Biol., 19.","DOI":"10.1186\/s12915-021-01062-9"},{"key":"ref_4","first-page":"89","article-title":"Teratogenesis of alcohol","volume":"29","author":"Spagnolo","year":"1993","journal-title":"Ann. Dell\u2019istituto Super. Sanita"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1097\/GRF.0000000000000414","article-title":"Alcohol Use in Pregnancy","volume":"62","author":"DeJong","year":"2019","journal-title":"Clin. Obstet. Gynecol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5233","DOI":"10.1038\/s41598-021-83942-2","article-title":"Evaluation of the German biographic screening interview for fetal alcohol spectrum disorder (BSI-FASD)","volume":"11","author":"Widder","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1016\/S1701-2163(16)34633-3","article-title":"Alcohol Use and Pregnancy Consensus Clinical Guidelines","volume":"32","author":"Carson","year":"2010","journal-title":"J. Obstet. Gynaecol. Can."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1097\/CHI.0b013e3181bc72e3","article-title":"A Candidate Gene Analysis of Methylphenidate Response in Attention-Deficit\/Hyperactivity Disorder","volume":"48","author":"McGough","year":"2009","journal-title":"J. Am. Acad. Child Adolesc. Psychiatry"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1097\/00007691-200304000-00002","article-title":"Children of Alcoholic Parents\u2014Observed Anomalies: Discussion of 127 Cases","volume":"25","author":"Lemoine","year":"2003","journal-title":"Ther. Drug Monit."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1177\/15353702-0323006-03","article-title":"Fetal Alcohol Spectrum Disorders: An Overview with Emphasis on Changes in Brain and Behavior","volume":"230","author":"Riley","year":"2005","journal-title":"Exp. Biol. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/bdrc.20200","article-title":"The effects of alcohol on fetal development","volume":"93","author":"Jones","year":"2011","journal-title":"Birth Defects Res. Part C Embryo Today Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1111\/jcpp.12451","article-title":"Research Review: Executive function deficits in fetal alcohol spectrum disorders and attention-deficit\/hyperactivity disorder\u2014A meta-analysis","volume":"57","author":"Kingdon","year":"2015","journal-title":"J. Child Psychol. Psychiatry"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1017\/S1355617799555082","article-title":"Implicit and explicit memory functioning in children with heavy prenatal alcohol exposure","volume":"5","author":"Mattson","year":"1999","journal-title":"J. Int. Neuropsychol. Soc."},{"key":"ref_14","first-page":"51","article-title":"The Quest for a Neurobehavioral Profile of Heavy Prenatal Alcohol Exposure","volume":"34","author":"Mattson","year":"2011","journal-title":"Alcohol Res. Health J. Natl. Inst. Alcohol Abus. Alcohol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1111\/acer.14040","article-title":"Fetal Alcohol Spectrum Disorders: A Review of the Neurobehavioral Deficits Associated with Prenatal Alcohol Exposure","volume":"43","author":"Mattson","year":"2019","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_16","first-page":"1","article-title":"Guidelines for identifying and referring persons with fetal alcohol syndrome","volume":"54","author":"Bertrand","year":"2005","journal-title":"MMWR. Recomm. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1111\/j.1530-0277.1995.tb01024.x","article-title":"Specific Impairments in Self-Regulation in Children Exposed to Alcohol Prenatally","volume":"19","author":"Kodituwakku","year":"1995","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1111\/j.1530-0277.1990.tb01223.x","article-title":"Attention deficits in children exposed to alcohol prenatally","volume":"14","author":"Nanson","year":"1990","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1111\/j.1530-0277.1994.tb00904.x","article-title":"Maternal drinking during pregnancy: Attention and short-term memory in 14-year-old offspring-a longitudinal prospective Study","volume":"18","author":"Streissguth","year":"1994","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Burd, L. (2016). FASD and ADHD: Are they related and How?. BMC Psychiatry, 16.","DOI":"10.1186\/s12888-016-1028-x"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Popova, S., Lange, S., Burd, L., and Rehm, J. (2012). Health care burden and cost associated with fetal alcohol syndrome: Based on official Canadian data. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0043024"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1093\/alcalc\/agv117","article-title":"The Economic Burden of Fetal Alcohol Spectrum Disorder in Canada in 2013","volume":"51","author":"Popova","year":"2015","journal-title":"Alcohol Alcohol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/j.ntt.2003.07.014","article-title":"Fetal alcohol syndrome: Neuropsychiatric phenomics","volume":"25","author":"Burd","year":"2003","journal-title":"Neurotoxicol. Teratol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"10391","DOI":"10.1038\/s41598-017-10912-y","article-title":"Pharmacogenetics of methylphenidate in childhood attention-deficit\/hyperactivity disorder: Long-term effects","volume":"7","author":"Carballo","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"108817","DOI":"10.1016\/j.drugalcdep.2021.108817","article-title":"Cortical gyrification in children with attention deficit-hyperactivity disorder and prenatal alcohol exposure","volume":"225","author":"Kilpatrick","year":"2021","journal-title":"Drug Alcohol Depend."},{"key":"ref_26","first-page":"678","article-title":"Using Meta-analysis to Compare the Efficacy of Medications for Attention-Defcit\/Hyperactivity Disorder in Youths","volume":"34","author":"Faraone","year":"2009","journal-title":"Pharm. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1177\/1087054714559643","article-title":"Long-Term Efficacy of Methylphenidate Immediate-Release for the Treatment of Childhood ADHD","volume":"21","author":"Maia","year":"2016","journal-title":"J. Atten. Disord."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1016\/j.ejphar.2015.07.044","article-title":"Psychostimulants affect dopamine transmission through both dopamine transporter-dependent and independent mechanisms","volume":"764","author":"Gevorkiana","year":"2015","journal-title":"Eur. J. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1002\/1096-8628(20010108)105:1<84::AID-AJMG1068>3.0.CO;2-Q","article-title":"5?-Untranslated region of the dopamine D4 receptor gene and attention-deficit hyperactivity disorder","volume":"105","author":"Barr","year":"2001","journal-title":"Am. J. Med Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1016\/j.neuroimage.2009.12.041","article-title":"Dopamine transporter gene variation modulates activation of striatum in youth with ADHD","volume":"53","author":"Schulz","year":"2010","journal-title":"NeuroImage"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1002\/ajmg.b.31132","article-title":"Effect of dopamine transporter genotype on caudate volume in childhood ADHD and controls","volume":"156","author":"Shook","year":"2010","journal-title":"Am. J. Med Genet. Part B Neuropsychiatr. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/B978-0-444-53884-0.00032-4","article-title":"Biological and social influences on cognitive control processes dependent on prefrontal cortex","volume":"189","author":"Diamond","year":"2011","journal-title":"Prog. Brain Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.psychres.2019.06.001","article-title":"Analysis of methylation and -141C Ins\/Del polymorphisms of the dopamine receptor D2 gene in patients with schizophrenia","volume":"278","author":"Funahashi","year":"2019","journal-title":"Psychiatry Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3129","DOI":"10.2147\/NDT.S118614","article-title":"Associations between dopamine D2 receptor gene polymorphisms and schizophrenia risk: A PRISMA compliant meta-analysis","volume":"12","author":"He","year":"2016","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"275","DOI":"10.3892\/br.2014.220","article-title":"Polymorphisms of DRD2 and DRD3 genes and Parkinson\u2019s disease: A meta-analysis","volume":"2","author":"Dai","year":"2014","journal-title":"Biomed. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.psychres.2011.09.024","article-title":"A DRD2 and ANKK1 haplotype is associated with nicotine dependence","volume":"196","author":"Voisey","year":"2012","journal-title":"Psychiatry Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e1914940","DOI":"10.1001\/jamanetworkopen.2019.14940","article-title":"Assessment of the Association of D2 Dopamine Receptor Gene and Reported Allele Frequencies With Alcohol Use Disorders: A Systematic Review and Meta-analysis","volume":"2","author":"Jung","year":"2019","journal-title":"JAMA Netw. Open"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.neulet.2015.01.076","article-title":"Association between ANKK1 (rs1800497) polymorphism of DRD2 gene and attention deficit hyperactivity disorder: A meta-analysis","volume":"590","author":"Pan","year":"2015","journal-title":"Neurosci. Lett."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1007\/s12035-012-8278-5","article-title":"Role of dopamine receptors in ADHD: A systematic meta-analysis","volume":"45","author":"Wu","year":"2012","journal-title":"Mol. Neurobiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"65","DOI":"10.3109\/15622975.2010.543431","article-title":"Dopaminergic system genes in childhood aggression: Possible role for DRD2","volume":"13","author":"Zai","year":"2011","journal-title":"World J. Biol. Psychiatry"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1007\/s40263-020-00702-y","article-title":"Genetic Influence on Efficacy of Pharmacotherapy for Pediatric Attention-Deficit\/Hyperactivity Disorder: Overview and Current Status of Research","volume":"34","author":"Elsayed","year":"2020","journal-title":"CNS Drugs"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1097\/FPC.0b013e32835693f7","article-title":"Association of COMT, MTHFR, and SLC19A1(RFC-1) polymorphisms with homocysteine blood levels and cognitive impairment in Parkinson\u2019s disease","volume":"22","author":"Kurzawski","year":"2012","journal-title":"Pharmacogenetics Genom."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3902","DOI":"10.1093\/cercor\/bhy269","article-title":"The Effects of COMT Polymorphism on Cortical Thickness and Surface Area Abnormalities in Children with ADHD","volume":"29","author":"Jung","year":"2018","journal-title":"Cereb. Cortex"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4850","DOI":"10.1038\/s41598-017-04579-8","article-title":"Catechol-O-methyltransferase polymorphism is associated with the cortico-cerebellar functional connectivity of executive function in children with attention-deficit\/hyperactivity disorder","volume":"7","author":"Mizuno","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1038\/mp.2017.234","article-title":"Pharmacogenetics predictors of methylphenidate efficacy in childhood ADHD","volume":"23","author":"Myer","year":"2017","journal-title":"Mol. Psychiatry"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1097\/YIC.0b013e328306a977","article-title":"Association of the catechol-O-methyltransferase polymorphism with methylphenidate response in a classroom setting in children with attention-deficit hyperactivity disorder","volume":"23","author":"Cheon","year":"2008","journal-title":"Int. Clin. Psychopharmacol."},{"key":"ref_47","first-page":"51","article-title":"Candidate gene studies of ADHD: A meta-analytic review","volume":"126","author":"Gizer","year":"2009","journal-title":"Qual. Life Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"335","DOI":"10.12740\/PP\/OnlineFirst\/62014","article-title":"Validation of the Polish version of the Washington 4-digit code for the assessment of Fetal Alcohol Spectrum Disorders","volume":"51","author":"Klecka","year":"2017","journal-title":"Psychiatr. Polska"},{"key":"ref_49","unstructured":"Kutchins, H., and Kirk, S.A. (1994). DSM-IV: Diagnostic and Statistical Manual of Mental Disorders, American Psychiatric Association. [4th ed.]."},{"key":"ref_50","unstructured":"Pu\u017cy\u0144ski, S., and Wci\u00f3rka, J. (2000). The Classification of Mental and Behaviour in ICD-10, University Medical Publishing \u201cVesalius\u201d. [2nd ed.]."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1177\/070674371005500506","article-title":"Clinical Response to Methylphenidate in Children Diagnosed with Attention-Deficit Hyperactivity Disorder and Comorbid Psychiatric Disorders","volume":"55","author":"Grizenko","year":"2010","journal-title":"Can. J. Psychiatry"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/S2215-0366(18)30269-4","article-title":"Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: A systematic review and network meta-analysis","volume":"5","author":"Cortese","year":"2018","journal-title":"Lancet Psychiatry"},{"key":"ref_53","unstructured":"Streissguth, A., and Kanter, J. (1997). A study of stimulant medication in children with FAS. Overcoming and Preventing Secondary Disabilities in Fetal Alcohol Syndrome and Fetal Alcohol Effects, University of Washington Press."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1089\/cap.1998.8.39","article-title":"Effectiveness of methylphenidate in native American children with fetal alcohol syndrome and attention deficit\/hyperactivity disorder: A controlled pilot study","volume":"8","author":"Oesterheld","year":"1998","journal-title":"J. Child Adolesc. Psychopharmacol."},{"key":"ref_55","first-page":"90","article-title":"Psychostimulant clinical response in fetal alcohol syndrome","volume":"45","author":"Koplin","year":"2000","journal-title":"Can. J. Psychiatry"},{"key":"ref_56","unstructured":"(2022, February 04). Attention Deficit Hyperactivity Disorder: Diagnosis and Management. Available online: https:\/\/www.nice.org.uk\/guidance\/ng87\/resources\/attention-deficit-hyperactivi-ty-disorder-diagnosis-and-management-pdf-1837699732933."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1177\/0269881114548438","article-title":"Predicting methylphenidate response in attention deficit hyperactivity disorder: A preliminary study","volume":"29","author":"Johnston","year":"2014","journal-title":"J. Psychopharmacol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"509","DOI":"10.2147\/NDT.S7256","article-title":"Distinguishing between attention-deficit hyperactivity and fetal alcohol spectrum disorders in children: Clinical guidelines","volume":"6","author":"Peadon","year":"2010","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41398-021-01473-w","article-title":"Genetic variations influence brain changes in patients with attention-deficit hyperactivity disorder","volume":"11","author":"Yadav","year":"2021","journal-title":"Transl. Psychiatry"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1002\/ajmg.b.30586","article-title":"Response to methylphenidate in adults with ADHD is associated with a polymorphism inSLC6A3 (DAT1)","volume":"147","author":"Kooij","year":"2008","journal-title":"Am. J. Med Genet. Part B Neuropsychiatr. Genet."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1097\/JCP.0b013e318270e727","article-title":"No significant association between genetic variants in 7 candidate genes and response to methylphenidate treatment in adult patients with ADHD","volume":"32","author":"Contini","year":"2012","journal-title":"J. Clin. Psychopharmacol."},{"key":"ref_62","first-page":"561","article-title":"New perspectives in the treatment of psychiatric diseases-pharmacogenetic studies of dopaminergic and serotonergic neurotransmission systems","volume":"4","author":"Samochowiec","year":"2000","journal-title":"Psychiatr. Pol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/npp.2010.96","article-title":"Neurogenetics and pharmacology of learning, motivation, and cognition","volume":"36","author":"Frank","year":"2010","journal-title":"Neuropsychopharmacology"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.drugalcdep.2015.03.003","article-title":"A review of pharmacogenetic studies of substance-related disorders","volume":"152","author":"Jones","year":"2015","journal-title":"Drug Alcohol Depend."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1176\/appi.ajp.2008.07111774","article-title":"Neurobiology of Aggression and Violence","volume":"165","author":"Siever","year":"2008","journal-title":"Am. J. Psychiatry"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1093\/schbul\/sbv032","article-title":"Interaction Between Functional Genetic Variation of DRD2 and Cannabis Use on Risk of Psychosis","volume":"41","author":"Colizzi","year":"2015","journal-title":"Schizophr. Bull."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1097\/00008571-199712000-00006","article-title":"D2 dopamine receptor gene (DRD2) Taql A polymorphism: Reduced dopamine D2 receptor binding in the human striatum associated with the A1 allele","volume":"7","author":"Thompson","year":"1997","journal-title":"Pharmacogenetics"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1089\/cap.2008.046","article-title":"Dopamine-Related Genotypes and the Dose\u2013Response Effect of Methylphenidate on Eating in Attention-Deficit\/Hyperactivity Disorder Youths","volume":"19","author":"Leddy","year":"2009","journal-title":"J. Child Adolesc. Psychopharmacol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/tpj.2013.23","article-title":"Positive effects of methylphenidate on hyperactivity are moderated by monoaminergic gene variants in children with autism spectrum disorders","volume":"14","author":"McCracken","year":"2013","journal-title":"Pharmacogenomics J."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1097\/00008571-199606000-00007","article-title":"Human catechol-O-methyltransferase pharmacogenetics: Description of a functional polymorphism and its potential application to neuropsychiatric disorders","volume":"6","author":"Lachman","year":"1996","journal-title":"Pharmacogenetics"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1016\/j.jaac.2011.08.002","article-title":"Pharmacogenetic Predictors of Methylphenidate Dose-Response in Attention-Deficit\/Hyperactivity Disorder","volume":"50","author":"Froehlich","year":"2011","journal-title":"J. Am. Acad. Child Adolesc. Psychiatry"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"213","DOI":"10.2165\/00023210-200822030-00003","article-title":"Adverse effects of pharmacotherapies for attention-deficit hyperactivity disorder: Epidemiology, pre-vention and management","volume":"22","author":"Graham","year":"2008","journal-title":"CNS Drugs"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1007\/s00228-012-1390-7","article-title":"Treatment discontinuation with methylphenidate in adults with attention deficit hyperactivity disorder: A meta-analysis of randomized clinical trials","volume":"69","author":"Castells","year":"2012","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_74","first-page":"278","article-title":"Pharmacogenetic influences on the response to pharmacological treatment in autism spectrum disorders","volume":"5","author":"Hervas","year":"2021","journal-title":"J. Transl. Genet. Genom."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S0166-4328(01)00433-8","article-title":"Pharmacokinetic and pharmacodynamic properties of stimulants: Implications for the design of new treatments for ADHD","volume":"130","author":"Swanson","year":"2001","journal-title":"Behav. Brain Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.ijdevneu.2017.06.002","article-title":"Effects of prenatal binge-like ethanol exposure and maternal stress on postnatal morphological development of hippocampal neurons in rats","volume":"61","author":"Elibol","year":"2017","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_77","first-page":"541","article-title":"An interaction between a polymorphism of the serotonin transporter (5HTT) gene and the clinical picture of adolescents with combined type of ADHD (hyper-kinetic disorder) and youth drinking","volume":"48","author":"Gorzkowska","year":"2014","journal-title":"Psychiatr. Pol."},{"key":"ref_78","first-page":"97","article-title":"Advances in Diagnosis and Treatment of Fetal Alcohol Spectrum Dis-orders From Animal Models to Human Studies","volume":"37","author":"Murawski","year":"2015","journal-title":"Alcohol Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1097\/PSY.0000000000000481","article-title":"Joint impact of early life adversity and COMT Val158Met (rs4680) genotypes on the adult cortisol response to psychological stress","volume":"79","author":"Lovallo","year":"2017","journal-title":"Psychsom. Med."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/19\/8\/4479\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:50:16Z","timestamp":1760136616000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/19\/8\/4479"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,8]]},"references-count":79,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["ijerph19084479"],"URL":"https:\/\/doi.org\/10.3390\/ijerph19084479","relation":{},"ISSN":["1660-4601"],"issn-type":[{"type":"electronic","value":"1660-4601"}],"subject":[],"published":{"date-parts":[[2022,4,8]]}}}