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document
Disorder-dissociated effects of fluoxetine on brain function of working memory in attention deficit hyperactivity disorder and autism spectrum disorder . BACKGROUND Attention deficit hyperactivity disorder ( ADHD ) and autism spectrum disorder ( ASD ) are often co-morbid and share performance and brain dysfunctions during working memory ( WM ) . Serotonin agonists modulate WM and there is evidence of positive behavioural effects in both disorders . We therefore used functional magnetic resonance imaging ( fMRI ) to investigate shared and disorder-specific brain dysfunctions of WM in these disorders , and the effects of a single dose of the selective serotonin reuptake inhibitor ( SSRI ) fluoxetine . METHOD Age-matched boys with ADHD ( n = 17 ) , ASD ( n = 17 ) and controls ( n = 22 ) were compared using fMRI during an N-back WM 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 on performance and brain function . To test for normalization effects of brain dysfunctions , patients under each drug condition were compared to controls . RESULTS Under placebo , relative to controls , both ADHD and ASD boys shared underactivation in the right dorsolateral prefrontal cortex ( DLPFC ) . Fluoxetine significantly normalized the DLPFC underactivation in ASD relative to controls whereas it increased posterior cingulate cortex ( PCC ) deactivation in ADHD relative to control boys . Within-patient analyses showed inverse effects of fluoxetine on PCC deactivation , which it enhanced in ADHD and decreased in ASD . CONCLUSIONS The findings show that fluoxetine modulates brain activation during WM in a disorder-specific manner by normalizing task-positive DLPFC dysfunction in ASD boys and enhancing task-negative default mode network ( DMN ) deactivation in ADHD .
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Intervention_Pharmacological
fluoxetine
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Intervention_Pharmacological
serotonin reuptake inhibitor ( SSRI ) fluoxetine
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Intervention_Pharmacological
dose of fluoxetine
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Participant_Condition
attention deficit hyperactivity disorder
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Participant_Condition
autism spectrum disorder .
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Participant_Age
Age-matched
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Participant_Sex
boys
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Participant_Sample-size
17
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Participant_Sample-size
17
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Participant_Sample-size
22
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Participant_Condition
ASD