title: The effects of acute fluoxetine administration on temporal discounting in youth with ADHD.
abstract: BACKGROUND
  Serotonin is under-researched in attention deficit hyperactivity disorder (ADHD), despite accumulating evidence for its involvement in impulsiveness and the disorder. Serotonin further modulates temporal discounting (TD), which is typically abnormal in ADHD relative to healthy subjects, underpinned by reduced fronto-striato-limbic activation. This study tested whether a single acute dose of the selective serotonin reuptake inhibitor (SSRI) fluoxetine up-regulates and normalizes reduced fronto-striato-limbic neurofunctional activation in ADHD during TD.
  
  
  METHODS
  Twelve boys with ADHD were scanned twice in a placebo-controlled randomized design under either fluoxetine (between 8 and 15 mg, titrated to weight) or placebo while performing an individually adjusted functional magnetic resonance imaging TD task. Twenty healthy controls were scanned once. Brain activation was compared in patients under either drug condition and compared to controls to test for normalization effects.
  
  
  RESULTS
  Repeated-measures whole-brain analysis in patients revealed significant up-regulation with fluoxetine in a large cluster comprising right inferior frontal cortex, insula, premotor cortex and basal ganglia, which further correlated trend-wise with TD performance, which was impaired relative to controls under placebo, but normalized under fluoxetine. Fluoxetine further down-regulated default mode areas of posterior cingulate and precuneus. Comparisons between controls and patients under either drug condition revealed normalization with fluoxetine in right premotor-insular-parietal activation, which was reduced in patients under placebo.
  
  
  CONCLUSIONS
  The findings show that a serotonin agonist up-regulates activation in typical ADHD dysfunctional areas in right inferior frontal cortex, insula and striatum as well as down-regulating default mode network regions in the context of impulsivity and TD.
authors.affiliation: Department of Child & Adolescent Psychiatry,Institute of Psychiatry, Psychology and Neuroscience,King's College,London,UK.
authors.forename: C O
authors.initials: CO
authors.lastname: Carlisi
authors.affiliation: Department of Child & Adolescent Psychiatry,Institute of Psychiatry, Psychology and Neuroscience,King's College,London,UK.
authors.forename: K
authors.initials: K
authors.lastname: Chantiluke
authors.affiliation: Department of Child & Adolescent Psychiatry,Institute of Psychiatry, Psychology and Neuroscience,King's College,London,UK.
authors.forename: L
authors.initials: L
authors.lastname: Norman
authors.affiliation: Department of Child & Adolescent Psychiatry,Institute of Psychiatry, Psychology and Neuroscience,King's College,London,UK.
authors.forename: A
authors.initials: A
authors.lastname: Christakou
authors.affiliation: South London and Maudsley NHS Trust,London,UK.
authors.forename: N
authors.initials: N
authors.lastname: Barrett
authors.affiliation: Department of Neuroimaging,Institute of Psychiatry, Psychology and Neuroscience,King's College,London,UK.
authors.forename: V
authors.initials: V
authors.lastname: Giampietro
authors.affiliation: Department of Neuroimaging,Institute of Psychiatry, Psychology and Neuroscience,King's College,London,UK.
authors.forename: M
authors.initials: M
authors.lastname: Brammer
authors.affiliation: Department of Neuroimaging,Institute of Psychiatry, Psychology and Neuroscience,King's College,London,UK.
authors.forename: A
authors.initials: A
authors.lastname: Simmons
authors.affiliation: Department of Child & Adolescent Psychiatry,Institute of Psychiatry, Psychology and Neuroscience,King's College,London,UK.
authors.forename: K
authors.initials: K
authors.lastname: Rubia
mesh_terms: D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000503:physiopathology; D001479:Basal Ganglia / Q000187:drug effects* / Q000503:physiopathology; D001931:Brain Mapping; D016022:Case-Control Studies; D002648:Child; D065786:Delay Discounting / Q000187:drug effects*; D005473:Fluoxetine / Q000008:administration & dosage*; D005625:Frontal Lobe / Q000187:drug effects* / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D011569:Psychiatric Status Rating Scales; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage*; D016896:Treatment Outcome; D006113:United Kingdom; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Attention deficit hyperactivity disorder; basal ganglia; delay discounting; functional magnetic resonance imaging; impulsiveness; insula; right inferior frontal cortex; selective serotonin reuptake inhibitor; serotonin; temporal discounting