Inverse Effect of Fluoxetine on Medial Prefrontal Cortex Activation During Reward Reversal in ADHD and Autism.
Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) share brain function abnormalities during cognitive flexibility. Serotonin is involved in both disorders, and selective serotonin reuptake inhibitors (SSRIs) can modulate cognitive flexibility and improve behavior in both disorders. Thus, this study investigates shared and disorder-specific brain dysfunctions in these 2 disorders during reward reversal, and the acute effects of an SSRI on these. Age-matched boys with ADHD (15), ASD (18), and controls (21) were compared with functional magnetic resonance imaging (fMRI) during a reversal task. Patients were scanned twice, under either an acute dose of Fluoxetine or placebo in a double-blind, placebo-controlled randomized design. Repeated-measures analyses within patients assessed drug effects. Patients under each drug condition were compared with controls to assess normalization effects. fMRI data showed that, under placebo, ASD boys underactivated medial prefrontal cortex (mPFC), compared with control and ADHD boys. Both patient groups shared decreased precuneus activation. Under Fluoxetine, mPFC activation was up-regulated and normalized in ASD boys relative to controls, but down-regulated in ADHD boys relative to placebo, which was concomitant with worse task performance in ADHD. Fluoxetine therefore has inverse effects on mPFC activation in ASD and ADHD during reversal learning, suggesting dissociated underlying serotonin abnormalities.
Department of Child and Adolescent Psychiatry.
Kaylita
K
Chantiluke
South London and Maudsley NHS Trust.
Nadia
N
Barrett
Department of Neuroimaging, Institute of Psychiatry.
Vincent
V
Giampietro
Department of Neuroimaging, Institute of Psychiatry.
Michael
M
Brammer
Department of Neuroimaging, Institute of Psychiatry NIHR Biomedical Research Centre for Mental Health at South London and Maudsley NHS Trust.
Andrew
A
Simmons
Department of Forensic and Developmental Sciences, King's College London, London, UK.
Declan G
DG
Murphy
Department of Child and Adolescent Psychiatry.
Katya
K
Rubia
D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000503:physiopathology; D001321:Autistic Disorder / Q000188:drug therapy* / Q000503:physiopathology; D001931:Brain Mapping; D002648:Child; D004311:Double-Blind Method; D005473:Fluoxetine / Q000627:therapeutic use*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000503:physiopathology; D012193:Reversal Learning / Q000187:drug effects* / Q000502:physiology; D012201:Reward; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*
D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors
ADHD; ASD; cognitive flexibility; fMRI; serotonin