Methylphenidate treatment status and subclinical atherosclerosis in children and adolescents with ADHD: a cross-sectional comparative study.

Abstract

Attention-deficit/hyperactivity disorder (ADHD) has been increasingly associated with chronic inflammation and may contribute to early cardiovascular risk. Although subclinical atherosclerosis has been documented in drug-naive children with ADHD, whether methylphenidate treatment status is associated with differences in subclinical atherosclerotic markers remains unknown. This study aimed to evaluate the association between methylphenidate treatment status and subclinical atherosclerosis in children and adolescents with ADHD. This cross-sectional comparative observational study enrolled 65 MPH-treated and 65 medication-naïve children and adolescents aged 8-17 years with a DSM-5 diagnosis of ADHD. Subclinical atherosclerosis was evaluated echocardiographically through measurements of carotid intima-media thickness (cIMT), epicardial adipose tissue (EAT) thickness, and periaortic adipose tissue (PAT) thickness. Group differences were analyzed using multivariate analysis of covariance (MANCOVA) and subsequent analyses of covariance (ANCOVA), adjusting for age, sex, body mass index, mean blood pressure, and total cholesterol. Following covariate adjustment, PAT thickness was the only parameter that remained significantly higher in the medication-naïve group compared to the MPH-treated group; adjusted differences in cIMT and EAT thickness did not reach statistical significance. Within the MPH-treated group, methylphenidate dose was positively correlated with EAT and PAT thickness, duration of treatment was associated with PAT thickness, and duration of ADHD symptoms was correlated with all three echocardiographic parameters. In this cross-sectional comparative study, medication-naïve children and adolescents with ADHD had higher periaortic adipose tissue thickness compared to methylphenidate-treated patients, independent of major cardiovascular confounders, whereas no significant adjusted differences were observed for cIMT or EAT thickness. The positive associations between methylphenidate dose, treatment duration, and vascular risk markers within the treated group highlight the importance of cardiovascular monitoring in children receiving long-term MPH treatment. These findings should be interpreted within the limitations of the cross-sectional design, which precludes causal inference, and the observed associations may reflect residual confounding rather than direct effects of methylphenidate treatment status on subclinical atherosclerosis.