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Emotional dysregulation (ED) and callous unemotional (CU) traits can be associated with ADHD in youth, influencing its natural history and outcome, but their effect on medication efficacy is unexplored. We examined whether two measures of baseline ED and CU traits, the Child Behavior Checklist-Dysregulation Profile (CBCL-DP) and the Antisocial Process Screening Device (APSD), respectively, were predictors of change of ADHD-Rating Scale (ADHD-RS) after a 4-week methylphenidate (MPH) monotherapy. 43 patients (37 males, 8–16 years, mean 9.9 ± 2.7 years) were included. Hierarchical linear regression models were used to explore whether CBCL-DP and APSD might predict ADHD-RS score, controlling for baseline severity. Baseline CBCL-DP predicted higher post-treatment ADHD-RS scores in total and hyperactivity-impulsivity, but not in inattention subscale. Baseline APSD was not significantly related to ADHD-RS scores at the follow-up. Small sample size, lack of gender diversity, non-blind design and short period of observation. ED, assessed with that CBCL-DP, might be a negative predictor of change of hyperactive-impulsive symptoms after MPH treatment and should be systematically assessed at baseline. • Negative predictors of MPH treatment in youth with ADHD are poorly explored. • Emotional dysregulation might be a negative predictor of MPH short-term response. • Callous unemotional traits were not related to poorer response to MPH. • Emotional dysregulation should be systematically assessed in youth with ADHD. [ABSTRACT FROM AUTHOR]