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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 bot...

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Autores principales: Chantiluke, Kaylita, Barrett, Nadia, Giampietro, Vincent, Santosh, Paramala, Brammer, Michael, Simmons, Andrew, Murphy, Declan G., Rubia, Katya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4432080/
https://www.ncbi.nlm.nih.gov/pubmed/25533997
http://dx.doi.org/10.1007/s00213-014-3837-2
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author Chantiluke, Kaylita
Barrett, Nadia
Giampietro, Vincent
Santosh, Paramala
Brammer, Michael
Simmons, Andrew
Murphy, Declan G.
Rubia, Katya
author_facet Chantiluke, Kaylita
Barrett, Nadia
Giampietro, Vincent
Santosh, Paramala
Brammer, Michael
Simmons, Andrew
Murphy, Declan G.
Rubia, Katya
author_sort Chantiluke, Kaylita
collection PubMed
description 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00213-014-3837-2) contains supplementary material, which is available to authorized users.
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spelling pubmed-44320802015-05-19 Inverse fluoxetine effects on inhibitory brain activation in non-comorbid boys with ADHD and with ASD Chantiluke, Kaylita Barrett, Nadia Giampietro, Vincent Santosh, Paramala Brammer, Michael Simmons, Andrew Murphy, Declan G. Rubia, Katya Psychopharmacology (Berl) Original Investigation 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00213-014-3837-2) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2014-12-24 2015 /pmc/articles/PMC4432080/ /pubmed/25533997 http://dx.doi.org/10.1007/s00213-014-3837-2 Text en © The Author(s) 2014 https://creativecommons.org/licenses/by/4.0/ Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
spellingShingle Original Investigation
Chantiluke, Kaylita
Barrett, Nadia
Giampietro, Vincent
Santosh, Paramala
Brammer, Michael
Simmons, Andrew
Murphy, Declan G.
Rubia, Katya
Inverse fluoxetine effects on inhibitory brain activation in non-comorbid boys with ADHD and with ASD
title Inverse fluoxetine effects on inhibitory brain activation in non-comorbid boys with ADHD and with ASD
title_full Inverse fluoxetine effects on inhibitory brain activation in non-comorbid boys with ADHD and with ASD
title_fullStr Inverse fluoxetine effects on inhibitory brain activation in non-comorbid boys with ADHD and with ASD
title_full_unstemmed Inverse fluoxetine effects on inhibitory brain activation in non-comorbid boys with ADHD and with ASD
title_short Inverse fluoxetine effects on inhibitory brain activation in non-comorbid boys with ADHD and with ASD
title_sort inverse fluoxetine effects on inhibitory brain activation in non-comorbid boys with adhd and with asd
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4432080/
https://www.ncbi.nlm.nih.gov/pubmed/25533997
http://dx.doi.org/10.1007/s00213-014-3837-2
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