J Child Psychol Psychiatry. 2026 Aug 10. doi: 10.1111/jcpp.70217. Online ahead of print.
ABSTRACT
BACKGROUND: This study aimed to compare the effects of atomoxetine (ATX) and methylphenidate (MPH) on emotional dysregulation (ED) in children with attention deficit/hyperactivity disorder (ADHD), and to explore potential neural correlates underlying treatment-related changes.
METHODS: A total of 152 children with ADHD were randomly assigned to receive ATX (n = 76) or MPH (n = 76). After individualized dose titration, participants received a stable dose for 4 weeks. Emotional lability (EL) was the primary outcome, while emotion regulation strategies, ADHD symptoms, and overall illness severity were secondary outcomes. Mixed-effects linear models were applied to examine group differences across three time points (baseline, post-titration, and endpoint). Resting-state functional MRI data were acquired at baseline and endpoint and analyzed using whole-brain functional connectivity (FC) analysis with six amygdala subregions as seeds.
TRIAL REGISTRATION: ChiCTR2200062905; approved on August 23, 2022.
RESULTS: In both ATX and MPH groups, EL scores decreased significantly over time (β = -1.54, p < .001), with treatment effects in a similar range and no statistically significant between-group difference (MPH: d = -1.46; ATX: d = -0.93). After controlling for ADHD symptom improvement, treatment effects remained significant (β = -0.75, p < .001), suggesting that EL improvement was not solely accounted for by ADHD symptom reduction. Increased FC between the right basolateral amygdala and left orbital middle frontal gyrus (r = -0.46, p = .043), and between the left superficial amygdala and left middle cingulate cortex (r = -0.48, p = .031), was associated with EL changes and remained significant after controlling for ADHD symptom changes. No significant changes were found in self-reported emotion regulation strategies.
CONCLUSIONS: ATX and MPH both alleviate ED in children with ADHD, and these effects are not solely accounted for by improvements in ADHD symptoms. Increased amygdala-centered FC may be associated with medication-related ED improvements.
PMID:42576119 | DOI:10.1111/jcpp.70217
