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Inverse fluoxetine effects on inhibitory brain activation in non-comorbid boys with ADHD and with ASD . RATIONALE 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 . AIMS 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 .
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Intervention_Physical
functional magnetic resonance imaging
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Intervention_Physical
compared with fMRI during a stop task measuring motor inhibition .
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Intervention_Pharmacological
an acute dose of fluoxetine
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Intervention_Control
placebo
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Intervention_Control
placebo-controlled
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Outcome_Physical
inhibitory brain activation
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Outcome_Physical
motor response inhibition
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Outcome_Mental
behavioural effects
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Outcome_Physical
inhibitory brain dysfunctions
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Outcome_Physical
motor inhibition .
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Outcome_Adverse-effects
drug effects .
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Outcome_Mental
normalisation effects
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Outcome_Physical
overactivation in left and right inferior frontal cortex ( IFC )
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Outcome_Physical
underactivation in orbitofrontal cortex ( OFC ) and basal ganglia .
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Outcome_Physical
prefrontal dysfunctions
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Outcome_Physical
IFC and OFC activation
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Outcome_Physical
frontal lobe dysfunctions
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Outcome_Physical
frontal activation
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Outcome_Physical
frontal activation
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Participant_Sex
boys
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Participant_Condition
ADHD
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Participant_Condition
ASD
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Participant_Sex
boys
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Participant_Condition
ADHD
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Participant_Condition
ASD
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Participant_Condition
healthy controls
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Participant_Condition
ASD
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Participant_Sex
boys
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Participant_Condition
ADHD
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Participant_Sex
boys