title: Inverse fluoxetine effects on inhibitory brain activation in non-comorbid boys with ADHD and with ASD.
abstract: BACKGROUND
  Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are often comorbid and have both performance and brain dysfunctions during motor response inhibition. Serotonin agonists modulate motor response inhibition and have shown positive behavioural effects in both disorders.
  
  
  OBJECTIVE
  We therefore used functional magnetic resonance imaging (fMRI) to investigate the so far unknown shared and disorder-specific inhibitory brain dysfunctions in these two disorders, as well as the effects of a single dose of the selective serotonin reuptake inhibitor fluoxetine.
  
  
  METHODS
  Age-matched boys with ADHD (18), ASD (19) and healthy controls (25) were compared with fMRI during a stop task measuring motor inhibition. Patients were scanned twice, under either an acute dose of fluoxetine or placebo in a double-blind, placebo-controlled randomised design. Repeated measures analyses within patients assessed drug effects. To test for potential normalisation effects of brain dysfunctions, patients under each drug condition were compared to controls.
  
  
  RESULTS
  Under placebo, relative to controls, ASD boys showed overactivation in left and right inferior frontal cortex (IFC), while ADHD boys showed disorder-specific underactivation in orbitofrontal cortex (OFC) and basal ganglia. Under fluoxetine, the prefrontal dysfunctions were no longer observed, due to inverse effects of fluoxetine on these activations: fluoxetine downregulated IFC and OFC activation in ASD but upregulated them in ADHD.
  
  
  CONCLUSIONS
  The findings show that fluoxetine normalises frontal lobe dysfunctions in both disorders via inverse effects, downregulating abnormally increased frontal activation in ASD and upregulating abnormally decreased frontal activation in ADHD, potentially reflecting inverse baseline serotonin levels in both disorders.
authors.affiliation: Department of Child and Adolescent Psychiatry/MRC Center for Social, Genetic and Developmental Psychiatry (SGDP), Institute of Psychiatry, King's College London, 16 De Crespigny Park, PO46, London, SE5 8AF, UK.
authors.forename: Kaylita
authors.initials: K
authors.lastname: Chantiluke
authors.forename: Nadia
authors.initials: N
authors.lastname: Barrett
authors.forename: Vincent
authors.initials: V
authors.lastname: Giampietro
authors.forename: Paramala
authors.initials: P
authors.lastname: Santosh
authors.forename: Michael
authors.initials: M
authors.lastname: Brammer
authors.forename: Andrew
authors.initials: A
authors.lastname: Simmons
authors.forename: Declan G
authors.initials: DG
authors.lastname: Murphy
authors.forename: Katya
authors.initials: K
authors.lastname: Rubia
mesh_terms: D000293:Adolescent; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000523:psychology*; D000067877:Autism Spectrum Disorder / Q000188:drug therapy* / Q000523:psychology*; D001479:Basal Ganglia / Q000187:drug effects; D002648:Child; D004311:Double-Blind Method; D005473:Fluoxetine / Q000627:therapeutic use*; D005625:Frontal Lobe / Q000187:drug effects; D006801:Humans; D007266:Inhibition, Psychological; D007360:Intelligence / Q000502:physiology; D008279:Magnetic Resonance Imaging; D008297:Male; D009068:Movement / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects
chemical_list: D018687:Antidepressive Agents, Second-Generation; D005473:Fluoxetine