Shared and Unique Effects of Long-Term Administration of Methylphenidate and Atomoxetine on Degree Centrality in Medication-Naïve Children With Attention-Deficit/Hyperactive Disorder

Abstract

Background Although methylphenidate (MPH) and atomoxetine (ATX) can improve clinical symptoms and functional impairments in attention deficit/hyperactive disorder (ADHD), the underlying psychopharmacological mechanism have not been clearly elucidated. Therefore, we aimed to explore the shared and unique neurologic basis of these two medications in alleviating the clinical symptoms and functional impairments observed in ADHD. Methods Sixty-seven ADHD and 44 age-matched children with typical development were finally included and underwent resting-state functional magnetic resonance imaging (fMRI) scans at baseline. Then patients were assigned to MPH, ATX or untreated subgroups, based on the patients’ and their parents’ choice, for a 12-week follow-up, and underwent a second fMRI scan. The treatment effect on degree centrality (DC) was identified and correlated with clinical symptoms and functional impairments in the ADHD group. Results Both of MPH and ATX normalised the DC value in extensive brain regions mainly involving fronto-cingulo-parieto-cerebellum circuits. However, ATX showed limited significant effects on the cerebellum compared to ADHD at baseline. The improvements in clinical symptoms were correlated with increased DC in the right inferior temporal gyrus in both MPH and ATX subgroups, but showed opposite effects. The alleviation of functional impairments in the school/learning domain negatively correlated with decreased DC in the bilateral cerebellum after MPH treatment, while the family functional domain positively correlated with decreased DC in the cerebellum and negatively correlated with decreased DC in the postcentral gyrus after ATX treatment. Conclusions Both MPH and ATX can normalise abnormal brain functions that mainly involve the fronto-cingulo-parieto-cerebellum circuit in ADHD. Furthermore, the two medications affected shared and unique effective brain regions to alleviate clinical symptoms and functional impairment.

Meta-analysis of structural and functional alterations of brain in patients with attention-deficit/hyperactivity disorder

“…A recent study (120) suggests that inadequate neuromodulation of prefrontal-cerebellar circuits may underlie cognitive deficits in psychiatric disorders (including schizophrenia, bipolar disorder, and ADHD). In addition, studies (121) showed that both MPH and ATX can restore abnormal brain function in ADHD, mainly involving fronto-cingulo-parieto-cerebellum circuit. In conclusion, the brain changes of patients with ADHD may not be influenced by a single brain region but by multi-channel connections or there may be a certain brain region that is the most critical, which needs to be further studied by other methods such as brain structural network covariation and functional connectivity in the future.…”

Functional Imaging Derived ADHD Biotypes Based on Deep Clustering May Guide Personalized Medication Therapy

“…Specifically, both of the drugs have a moderating effect on the DM and cerebellum. DM serves as a core neuropathological mechanism of attention deficit behavior and cerebellar degree centrality was significantly associated with learning function performance 67 , 68 . Therefore, differential DM and cerebellar connectivity patterns between the two biotypes may influence drug responsiveness, consequently leading to varying symptom improvement outcomes, including inattention, total, and learning problem scores.…”