title: Atomoxetine Treatment Strengthens an Anti-Correlated Relationship between Functional Brain Networks in Medication-Naïve Adults with Attention-Deficit Hyperactivity Disorder: A Randomized Double-Blind Placebo-Controlled Clinical Trial.
abstract: BACKGROUND
  Although atomoxetine demonstrates efficacy in individuals with attention-deficit hyperactivity disorder, its treatment effects on brain resting-state functional connectivity remain unknown. Therefore, we aimed to investigate major brain functional networks in medication-naïve adults with attention-deficit hyperactivity disorder and the efficacy of atomoxetine treatment on resting-state functional connectivity.
  
  
  METHODS
  After collecting baseline resting-state functional MRI scans from 24 adults with attention-deficit hyperactivity disorder (aged 18-52 years) and 24 healthy controls (matched in demographic characteristics), the participants with attention-deficit hyperactivity disorder were randomly assigned to atomoxetine (n=12) and placebo (n=12) arms in an 8-week, double-blind, placebo-controlled trial. The primary outcome was functional connectivity assessed by a resting-state functional MRI. Seed-based functional connectivity was calculated and compared for the affective, attention, default, and cognitive control networks.
  
  
  RESULTS
  At baseline, we found atypical cross talk between the default, cognitive control, and dorsal attention networks and hypoconnectivity within the dorsal attention and default networks in adults with attention-deficit hyperactivity disorder. Our first-ever placebo-controlled clinical trial incorporating resting-state functional MRI showed that treatment with atomoxetine strengthened an anticorrelated relationship between the default and task-positive networks and modulated all major brain networks. The strengthened anticorrelations were associated with improving clinical symptoms in the atomoxetine-treated adults.
  
  
  CONCLUSIONS
  Our results support the idea that atypical default mode network task-positive network interaction plays an important role in the pathophysiology of adult attention-deficit hyperactivity disorder. Strengthening this atypical relationship following atomoxetine treatment suggests an important pathway to treat attention-deficit hyperactivity disorder.
authors.affiliation: Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan (Drs Lin and Gau); Graduate Institute of Brain and Mind Sciences, and Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan (Dr Gau).
authors.forename: Hsiang-Yuan
authors.initials: HY
authors.lastname: Lin
authors.affiliation: Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan (Drs Lin and Gau); Graduate Institute of Brain and Mind Sciences, and Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan (Dr Gau). 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; D000328:Adult; D000069445:Atomoxetine Hydrochloride / Q000627:therapeutic use*; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000503:physiopathology*; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology*; D001931:Brain Mapping; D016022:Case-Control Studies; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000187:drug effects / Q000503:physiopathology; D009483:Neuropsychological Tests; D011619:Psychotropic Drugs / Q000627:therapeutic use*; D012146:Rest; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018759:Adrenergic Uptake Inhibitors; D011619:Psychotropic Drugs; D000069445:Atomoxetine Hydrochloride
keywords: adult; atomoxetine; attention-deficit hyperactivity disorder; randomized double-blind placebo-controlled clinical trial; resting-state fMRI