title: Differential therapeutic effects of 12-week treatment of atomoxetine and methylphenidate on drug-naïve children with attention deficit/hyperactivity disorder: A counting Stroop functional MRI study.
abstract: Methylphenidate and atomoxetine are effective in treating attention-deficit/hyperactivity disorder (ADHD) with underlying distinct pharmacological mechanisms. To relate neural mechanisms to clinical response, we conducted a comparative trial to differentiate the changes in brain activation of drug-naïve children with ADHD when performing neuropsychological tasks after 12 weeks of pharmacotherapy. We randomized 50 drug-naïve children with ADHD, aged 7-17, to treatment with methylphenidate (n=25) or atomoxetine (n=25). These children were scanned twice with functional magnetic resonance imaging (fMRI) during the counting Stroop task before and after treatment. Focused attention and impulsivity were assessed twice by using the Conner's Continuous Performance Test (CCPT). The final sample for fMRI analysis comprised 20 in the methylphenidate group and 22 in the atomoxetine group. Atomoxetine decreased activations in the dorsal anterior cingulate cortex and dorsolateral prefrontal cortex, which correlated with improvement in focused attention assessed by the CCPT. In contrast, methylphenidate increased activations in the inferior frontal gyrus, which correlated with the decreasing severity of impulsivity assessed by the CCPT. The current findings suggest that differential therapeutic effects on neuronal changes induced by 12-week treatment atomoxetine and methylphenidate may contribute to behavioral improvement.
authors.affiliation: Department of Psychology, National Taiwan University, Taipei, Taiwan; Graduate Institute of Brain and Mind Sciences, and Neurobiology and Cognitive Science Center, National Taiwan University, Taipei, Taiwan.
authors.forename: Tai-Li
authors.initials: TL
authors.lastname: Chou
authors.affiliation: Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan; Graduate Institute of Brain and Mind Sciences, and Neurobiology and Cognitive Science Center, National Taiwan University, Taipei, Taiwan.
authors.forename: Seng
authors.initials: S
authors.lastname: Chia
authors.affiliation: Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
authors.forename: Chi-Yung
authors.initials: CY
authors.lastname: Shang
authors.affiliation: Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan; Department of Psychology, National Taiwan University, Taipei, Taiwan; Graduate Institute of Brain and Mind Sciences, and Neurobiology and Cognitive Science Center, National Taiwan University, Taipei, Taiwan. Electronic address: gaushufe@ntu.edu.tw.
authors.forename: Susan Shur-Fen
authors.initials: SS
authors.lastname: Gau
mesh_terms: D000293:Adolescent; D018759:Adrenergic Uptake Inhibitors / Q000627:therapeutic use*; D000704:Analysis of Variance; D000069445:Atomoxetine Hydrochloride / Q000627:therapeutic use*; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000473:pathology; D001921:Brain / Q000098:blood supply* / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D002648:Child; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008774:Methylphenidate / Q000627:therapeutic use*; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D011569:Psychiatric Status Rating Scales; D013624:Taiwan
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000697:Central Nervous System Stimulants; D008774:Methylphenidate; D000069445:Atomoxetine Hydrochloride; D010100:Oxygen
keywords: Atomoxetine; CANTAB; Counting Stroop fMRI; Focused attention; Inhibitory control; Methylphenidate