{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T04:18:17Z","timestamp":1780978697789,"version":"3.54.1"},"reference-count":52,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T00:00:00Z","timestamp":1643587200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Methylphenidate (MPH) is the treatment of first choice for developmental ADHD. To date, no reliable method to predict how patients will respond to MPH exists and conflicting results are reported on clinical characteristics of responders. The present study aims to give a more precise characterization of the patients who will respond best to MPH to help clinicians in defining the treatment plan. Age, neuropsychological functioning (i.e., attention and working memory), and behavioral\/emotional symptoms of 48 drug-na\u00efve children and adolescents with ADHD (42 boys and 6 girls, age-range 6\u201316 years, mean age 10.5 \u00b1 2.5 years, mean IQ 101.3 \u00b1 11.2) were studied to assess how these different characteristics affected a single-dose MPH response. Four hierarchical linear regression models were used to explore whether age, neuropsychological measures at baseline, and behavioral\/emotional symptoms could predict attention and working memory measures after a single-dose MPH administration. We found that improvement in attention and working memory was predicted by age, neuropsychological measures at baseline, and severity of ADHD symptoms. No behavioral and emotional symptoms predicted single-dose MPH response with the exception of conduct symptoms.<\/jats:p>","DOI":"10.3390\/ijerph19031640","type":"journal-article","created":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T09:59:21Z","timestamp":1643709561000},"page":"1640","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Moderators and Other Predictors of Methylphenidate Response in Children and Adolescents with ADHD"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1226-329X","authenticated-orcid":false,"given":"Barbara","family":"D\u2019Aiello","sequence":"first","affiliation":[{"name":"Child and Adolescent Neuropsychiatry Unit, Department of Neuroscience, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00146 Rome, Italy"},{"name":"Department of Human Science, LUMSA University, 00193 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Di Vara","sequence":"additional","affiliation":[{"name":"Child and Adolescent Neuropsychiatry Unit, Department of Neuroscience, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"De Rossi","sequence":"additional","affiliation":[{"name":"Child and Adolescent Neuropsychiatry Unit, Department of Neuroscience, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Italo","family":"Pretelli","sequence":"additional","affiliation":[{"name":"Child and Adolescent Neuropsychiatry Unit, Department of Neuroscience, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Vicari","sequence":"additional","affiliation":[{"name":"Child and Adolescent Neuropsychiatry Unit, Department of Neuroscience, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00146 Rome, Italy"},{"name":"Department of Life Science and Public Health, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Centro di Riabilitazione, Casa San Giuseppe, Opera Don Guanella, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3459-2601","authenticated-orcid":false,"given":"Deny","family":"Menghini","sequence":"additional","affiliation":[{"name":"Child and Adolescent Neuropsychiatry Unit, Department of Neuroscience, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1006\/cogp.1999.0734","article-title":"The Unity and Diversity of Executive Functions and Their Contributions to Complex \u201cFrontal Lobe\u201d Tasks: A Latent Variable Analysis","volume":"41","author":"Miyake","year":"2000","journal-title":"Cognit. Psychol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1080\/87565640701729755","article-title":"Stability of Executive Function Deficits in Girls with ADHD: A Prospective Longitudinal Follow up Study into Adolescence","volume":"33","author":"Biederman","year":"2007","journal-title":"Dev. Neuropsychol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/s10862-011-9217-x","article-title":"The Nature of Executive Function (EF) Deficits in Daily Life Activities in Adults with ADHD and Their Relationship to Performance on EF Tests","volume":"33","author":"Barkley","year":"2011","journal-title":"J. Psychopathol. Behav. Assess."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.biopsych.2013.10.005","article-title":"Effects of Methylphenidate on Cognitive Functions in Children and Adolescents with Attention-Deficit\/Hyperactivity Disorder: Evidence from a Systematic Review and a Meta-Analysis","volume":"76","author":"Coghill","year":"2014","journal-title":"Biol. Psychiatry"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"6769","DOI":"10.1073\/pnas.1115365109","article-title":"Distinct Neuropsychological Subgroups in Typically Developing Youth Inform Heterogeneity in Children with ADHD","volume":"109","author":"Fair","year":"2012","journal-title":"Proc. Natl. Acad. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1023\/A:1010329714819","article-title":"The Ecological Validity of Delay Aversion and Response Inhibition as Measures of Impulsivity in AD\/HD: A Supplement to the NIMH Multimodal Treatment Study of AD\/HD","volume":"29","author":"Solanto","year":"2001","journal-title":"J. Abnorm. Child Psychol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1016\/j.biopsych.2004.08.025","article-title":"Causal Heterogeneity in Attention-Deficit\/Hyperactivity Disorder: Do We Need Neuropsychologically Impaired Subtypes?","volume":"57","author":"Nigg","year":"2005","journal-title":"Biol. Psychiatry"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3104","DOI":"10.1016\/j.ridd.2013.06.032","article-title":"Proactive and Reactive Control of Movement Are Differently Affected in Attention Deficit Hyperactivity Disorder Children","volume":"34","author":"Pani","year":"2013","journal-title":"Res. Dev. Disabil."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1007\/s00787-009-0054-3","article-title":"Comparing the Efficacy of Stimulants for ADHD in Children and Adolescents Using Meta-Analysis","volume":"19","author":"Faraone","year":"2010","journal-title":"Eur. Child Adolesc. Psychiatry"},{"key":"ref_10","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_11","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1016\/S0006-3223(03)00609-7","article-title":"Methylphenidate Improves Response Inhibition in Adults with Attention-Deficit\/Hyperactivity Disorder","volume":"54","author":"Aron","year":"2003","journal-title":"Biol. Psychiatry"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1111\/j.1469-7610.2007.01761.x","article-title":"ADHD- and Medication-Related Brain Activation Effects in Concordantly Affected Parent-Child Dyads with ADHD: ADHD Frontostriatal Dysfunction","volume":"48","author":"Epstein","year":"2007","journal-title":"J. Child Psychol. Psychiatry"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1007\/s10802-009-9316-2","article-title":"Stimulant Treatment Reduces Lapses in Attention among Children with ADHD: The Effects of Methylphenidate on Intra-Individual Response Time Distributions","volume":"37","author":"Spencer","year":"2009","journal-title":"J. Abnorm. Child Psychol."},{"key":"ref_14","first-page":"27","article-title":"Effects of Methylphenidate on Reaction Time in Children with Attention Deficit Hyperactivity Disorder","volume":"56","author":"Guven","year":"2019","journal-title":"Arch. Neuropsychiatry"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1097\/00004583-200403000-00006","article-title":"Methylphenidate Improves Visual-Spatial Memory in Children with Attention-Deficit\/Hyperactivity Disorder","volume":"43","author":"Bedard","year":"2004","journal-title":"J. Am. Acad. Child Adolesc. Psychiatry"},{"key":"ref_16","first-page":"408","article-title":"Immediate Effects of Methylphenidate on Cognitive Attention Skills of Children with Attention-Deficit\u2013 Hyperactivity Disorder","volume":"47","author":"Hood","year":"2005","journal-title":"Dev. Med. Child Neurol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Farhat, L.C., Flores, J.M., Behling, E., Avila-Quintero, V.J., Lombroso, A., Cortese, S., Polanczyk, G.V., and Bloch, M.H. (2022). The Effects of Stimulant Dose and Dosing Strategy on Treatment Outcomes in Attention-Deficit\/Hyperactivity Disorder in Children and Adolescents: A Meta-Analysis. Mol. Psychiatry.","DOI":"10.1038\/s41380-021-01391-9"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Childress, A.C., Cutler, A.J., Po, M.D., DeSousa, N.J., Warrington, L.E., Sallee, F.R., and Incledon, B. (2021). Symptomatic and Functional Response and Remission From the Open-Label Treatment-Optimization Phase of a Study With DR\/ER-MPH in Children With ADHD. J. Clin. Psychiatry, 82.","DOI":"10.4088\/JCP.21m13914"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1016\/j.biopsych.2006.12.030","article-title":"The Neuropsychological Effects of Chronic Methylphenidate on Drug-Naive Boys with Attention-Deficit\/Hyperactivity Disorder","volume":"62","author":"Coghill","year":"2007","journal-title":"Biol. Psychiatry"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1097\/HRP.0000000000000122","article-title":"Pharmacological Treatment of ADHD in Addicted Patients: What Does the Literature Tell Us?","volume":"25","author":"Carpentier","year":"2017","journal-title":"Harv. Rev. Psychiatry"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.jsat.2012.07.001","article-title":"Predictors of Treatment Response in Adolescents with Comorbid Substance Use Disorder and Attention-Deficit\/Hyperactivity Disorder","volume":"44","author":"Tamm","year":"2013","journal-title":"J. Subst. Abuse Treat."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1007\/s00787-012-0286-5","article-title":"Amfetamine and Methylphenidate Medications for Attention-Deficit\/Hyperactivity Disorder: Complementary Treatment Options","volume":"21","author":"Hodgkins","year":"2012","journal-title":"Eur. Child Adolesc. Psychiatry"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"152178","DOI":"10.1016\/j.comppsych.2020.152178","article-title":"Emotional Dysregulation and Callous Unemotional Traits as Possible Predictors of Short-Term Response to Methylphenidate Monotherapy in Drug-Na\u00efve Youth with ADHD","volume":"100","author":"Masi","year":"2020","journal-title":"Compr. Psychiatry"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"160","DOI":"10.2174\/1745017901915010160","article-title":"Clinical and Neuropsychological Predictors of Methylphenidate Response in Children and Adolescents with ADHD: A Naturalistic Follow-up Study in a Spanish Sample","volume":"15","author":"Soutullo","year":"2019","journal-title":"Clin. Pract. Epidemiol. Ment. Health"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/s10802-016-0175-3","article-title":"Neurocognitive Predictors of ADHD Outcome: A 6-Year Follow-up Study","volume":"45","author":"Luman","year":"2017","journal-title":"J. Abnorm. Child Psychol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1177\/070674370200601S05","article-title":"Mechanism of Action of Methylphenidate: Insights from PET Imaging Studies","volume":"6","author":"Volkow","year":"2002","journal-title":"J. Atten. Disord."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Dovis, S., Van der Oord, S., Wiers, R.W., and Prins, P.J.M. (2015). Improving Executive Functioning in Children with ADHD: Training Multiple Executive Functions within the Context of a Computer Game. A Randomized Double-Blind Placebo Controlled Trial. PLOS ONE, 10.","DOI":"10.1371\/journal.pone.0121651"},{"key":"ref_28","unstructured":"Kaufman, J. (2019). K-SADS-PL DSM-5\u00ae: Intervista Diagnostica per La Valutazione Dei Disturbi Psicopatologici in Bambini e Adolescenti, Erickson."},{"key":"ref_29","unstructured":"Achenbach, T.M., and Rescorla, L.A. (2001). Manual for the ASEBA School-Age Forms & Profiles, University of Vermont, Research Center for Children, Youth, & Families."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1023\/A:1022602400621","article-title":"The Revised Conners\u2019 Parent Rating Scale (CPRS-R): Factor Structure, Reliability, and Criterion Validity","volume":"26","author":"Conners","year":"1998","journal-title":"J. Abnorm. Child Psychol."},{"key":"ref_31","unstructured":"Conners, C.K. (2000). Conners\u2019 Continuous Performance Test-II (CPT-II) Computer Program for Windows Technical Guide and Software Manual, Multi-Health Systems Inc."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1037\/h0043688","article-title":"Age Differences in Short-Term Retention of Rapidly Changing Information","volume":"55","author":"Kirchner","year":"1958","journal-title":"J. Exp. Psychol."},{"key":"ref_33","first-page":"65","article-title":"A Simple Sequentially Rejective Multiple Test Procedure","volume":"6","author":"Holm","year":"1979","journal-title":"Scand. J. Stat."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1111\/jcpp.12773","article-title":"Working Memory and Organizational Skills Problems in ADHD","volume":"59","author":"Kofler","year":"2018","journal-title":"J. Child Psychol. Psychiatry"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"15020","DOI":"10.1038\/nrdp.2015.20","article-title":"Attention-Deficit\/Hyperactivity Disorder","volume":"1","author":"Faraone","year":"2015","journal-title":"Nat. Rev. Dis. Primer"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1017\/S0033291720000574","article-title":"Comparative Meta-Analyses of Brain Structural and Functional Abnormalities during Cognitive Control in Attention-Deficit\/Hyperactivity Disorder and Autism Spectrum Disorder","volume":"50","author":"Lukito","year":"2020","journal-title":"Psychol. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1001\/jamapsychiatry.2016.0700","article-title":"Structural and Functional Brain Abnormalities in Attention-Deficit\/Hyperactivity Disorder and Obsessive-Compulsive Disorder: A Comparative Meta-Analysis","volume":"73","author":"Norman","year":"2016","journal-title":"JAMA Psychiatry"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Fantozzi, P., Sesso, G., Muratori, P., Milone, A., and Masi, G. (2021). Biological Bases of Empathy and Social Cognition in Patients with Attention-Deficit\/Hyperactivity Disorder: A Focus on Treatment with Psychostimulants. Brain Sci., 11.","DOI":"10.3390\/brainsci11111399"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1080\/09297040701220005","article-title":"Effect of Treatment with Stimulant Medication on Nonverbal Executive Function and Visuomotor Speed in Children with Attention Deficit\/Hyperactivity Disorder (ADHD)","volume":"14","author":"Snyder","year":"2008","journal-title":"Child Neuropsychol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1176\/jnp.13.3.326","article-title":"Effects of Stimulants on the Continuous Performance Test (CPT): Implications for CPT Use and Interpretation","volume":"13","author":"Riccio","year":"2001","journal-title":"J. Neuropsychiatry Clin. Neurosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1542\/peds.111.2.372","article-title":"Prescribing of Psychotropic Medications for Children by Australian Pediatricians and Child Psychiatrists","volume":"111","author":"Efron","year":"2003","journal-title":"Pediatrics"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1089\/cap.2020.0146","article-title":"Differential Treatment Effects of Methylphenidate and Atomoxetine on Executive Functions in Children with Attention-Deficit\/Hyperactivity Disorder","volume":"31","author":"Wu","year":"2021","journal-title":"J. Child Adolesc. Psychopharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1037\/pha0000374","article-title":"Baseline Performance Moderates Stimulant Effects on Cognition in Youth with ADHD","volume":"29","author":"Fosco","year":"2021","journal-title":"Exp. Clin. Psychopharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1089\/cap.2013.0031","article-title":"Baseline Severity of Parent-Perceived Inattentiveness Is Predictive of the Difference between Subjective and Objective Methylphenidate Responses in Children with Attention-Deficit\/Hyperactivity Disorder","volume":"23","author":"Park","year":"2013","journal-title":"J. Child Adolesc. Psychopharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1111\/j.1469-7610.2006.01633.x","article-title":"Acute Neuropsychological Effects of Methylphenidate in Stimulant Drug-Na\u00efve Boys with ADHD II\u2014Broader Executive and Non-Executive Domains: Acute Methylphenidate and Neuropsychology of ADHD","volume":"47","author":"Rhodes","year":"2006","journal-title":"J. Child Psychol. Psychiatry"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1177\/1087054714543924","article-title":"Cognitive Testing to Identify Children with ADHD Who Do and Do Not Respond to Methylphenidate","volume":"21","author":"Elliott","year":"2017","journal-title":"J. Atten. Disord."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"650","DOI":"10.3349\/ymj.2009.50.5.650","article-title":"Variability of Response Time as a Predictor of Methylphenidate Treatment Response in Korean Children with Attention Deficit Hyperactivity Disorder","volume":"50","author":"Lee","year":"2009","journal-title":"Yonsei Med. J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1586\/14737175.8.10.1563","article-title":"Improving Psychostimulant Adherence in Children with ADHD","volume":"8","author":"Charach","year":"2008","journal-title":"Expert Rev. Neurother."},{"key":"ref_49","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_50","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1016\/j.surg.2014.10.017","article-title":"A Systematic Review to Identify the Factors That Affect Failure to Rescue and Escalation of Care in Surgery","volume":"157","author":"Johnston","year":"2015","journal-title":"Surgery"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1089\/cap.2007.0011","article-title":"Long-Acting Methylphenidate Has an Effect on Aggressive Behavior in Children with Attention-Deficit\/Hyperactivity Disorder","volume":"17","author":"Sinzig","year":"2007","journal-title":"J. Child Adolesc. Psychopharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1089\/cap.2008.0115","article-title":"Do Sluggish Cognitive Tempo Symptoms Predict Response to Methylphenidate in Patients with Attention-Deficit\/Hyperactivity Disorder\u2013Inattentive Type?","volume":"19","author":"Ludwig","year":"2009","journal-title":"J. Child Adolesc. Psychopharmacol."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/19\/3\/1640\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:12:05Z","timestamp":1760134325000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/19\/3\/1640"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,31]]},"references-count":52,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["ijerph19031640"],"URL":"https:\/\/doi.org\/10.3390\/ijerph19031640","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,31]]}}}