The Neuroprotective Effects of Methylphenidate and Atomoxetine in Children With ADHD: A Lipidomic Study

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Background: Although the efficacy of methylphenidate and atomoxetine in ADHD is well documented in clinical trials, more studies are needed to clarify the neuroprotective effects of these two medications. Lipids exert important neuroprotective effects for optimal brain development and functioning. P...

Background: Although the efficacy of methylphenidate and atomoxetine in ADHD is well documented in clinical trials, more studies are needed to clarify the neuroprotective effects of these two medications. Lipids exert important neuroprotective effects for optimal brain development and functioning. Previous studies have demonstrated the significant connection between lipid dysregulation and the occurrence of ADHD. In addition, lipid dysregulation is closely related to the abnormal neural activity in individuals with ADHD. In this 3-year prospective project, we will perform a lipidomic analysis of blood before and after treatment with methylphenidate or atomoxetine, in order to identify the biological connections between the neuroprotective effects of medications and pathways of lipid metabolism in children with ADHD. Subjects and Methods: 70 drug-naïve patients with ADHD, aged 6-18, and 35 matched typically developing controls will be recruited in this project. We will randomly assign the 70 ADHD patients to two groups, 35 in the methylphenidate group and 35 in the atomoxetine group. Within the 12-week treatment period, we will use ADHDRS-IV, SNAP-IV, CBCL, YSR, CGI-ADHD-S, CGI-ADHD-I, SAICA, and Family APGAR-C to assess the improvement in the behavioral symptoms, and CPT and CANTAB to assess the improvement in the neuropsychological functioning. The blood sample will be collected, and we will use mass spectrometry to assess the medication-related change in lipidomic profiles. Anticipated Results: Using a prospective design, we anticipate that this study will delineate the effects of methylphenidate and atomoxetine on the lipidomic profiles in patients with ADHD. Furthermore, we will conduct pathway analysis to obtain crucial insight to the lipidomic regulation in neurophysiology of children with ADHD. We expect that the findings will increase our understanding of the neuroprotective effects of methylphenidate and atomoxetine in patients with ADHD, and identify the psychopharmacological mechanism of medication effects in ADHD via the pathways of lipid metabolism and regulation.

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