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

doi:10.1007/s00213-014-3837-2

Cited by 63Attention Deficit Hyperactivity DisorderNeural and Behavioral Psychology StudiesAutism Spectrum Disorder Research

Inverse fluoxetine effects on inhibitory brain activation in non-comorbid boys with ADHD and with ASD

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Chantiluke, Kaylita, Barrett, Nadia, Giampietro, Vincent, Santosh, Paramala, Brammer, Michael, Simmons, Andrew, Murphy, Declan G., Rubia, Katya·2015·Psychopharmacology

DOI 10.1007/s00213-014-3837-2PMC PMC4432080

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Abstract

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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IFC underactivation was found to be disorder-specific in individual fMRI studies compared to ASD.
“IFC underactivation was also found to be disorder-specific in individual fMRI studies compared to ASD (Chantiluke et al., 2015)”
From Cognitive Neuroscience of Attention Deficit Hyperactivity Disorder (ADHD) and Its Clinical Translation (2018) · cites this paper as Chantiluke et al., 2015
The Discussion says ADHD boys had lower IFC activation relative to ASD boys, but explicitly says they had no IFC underactivation relative to controls. The Results likewise show significantly higher left IFC activation in ASD than ADHD, while the right IFC difference was only a trend. The paper therefore supports the ADHD–ASD comparison, but characterizes the disorder-specific IFC finding as ASD overactivation rather than ADHD underactivation relative to controls. (LLM, conf=0.85)
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Auditory and visual word processing studied with fMRI
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Pauls AM O’Daly OG Rubia K Riedel WJ Williams SC Mehta MA Methylphenidate effects on prefrontal functioning during attentional-capture and response inhibition Biol Psychiatry 2012 72 142 149 10.1016/j.biopsych.2012.03.028 22552046 · DOI · Paper page

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Inverse Effect of Fluoxetine on Medial Prefrontal Cortex Activation During Reward Reversal in ADHD and Autism
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ADHD and ASD: distinct brain patterns of inhibition-related activation?
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Authors: Chantiluke, K., Barrett, N., Giampietro, V., Santosh, P., Brammer, M., Simmons, A., Murphy, D. G., & Rubia, K.
Affiliations: King's College London (GB)
South London and Maudsley NHS Foundation Trust (GB)
Corresponding author: Rubia, Katya
ORCID: Chantiluke, Kaylita
Giampietro, Vincent
Santosh, Paramala
Brammer, Michael
Simmons, Andrew
Murphy, Declan G.
Rubia, Katya
Venue: Psychopharmacology
Publisher: Springer Science and Business Media LLC
Published: 2014-12-24
Volume: 232
Issue: 12
Pages: 2071-2082
ISSN: 0033-3158 (ISSN-L)
1432-2072
DOI: 10.1007/s00213-014-3837-2
PMC: PMC4432080
OpenAlex: W2093733834
Cited by: 63
References: 80
Citations by year: 2026: 3 · 2025: 6 · 2024: 7 · 2023: 5 · 2022: 1 · 2021: 8 · 2020: 6 · 2019: 5 · 2018: 5 · 2017: 7 · 2016: 4 · 2015: 5 · 2014: 1
FWCI: 4.33
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0 (unspecified)
Locations: Psychopharmacology (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Research Portal (King's College London) (submittedVersion, other-oa)
Funders: Eli Lilly and Company
South London and Maudsley NHS Foundation Trust
European Federation of Pharmaceutical Industries and Associations
National Institute for Health and Care Research (RP-PG-0606-1045)
King's College London (115300)
European Commission (115300, FP7/2007)
Innovative Medicines Initiative (115300)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
Keywords: fluoxetine, attention deficit hyperactivity disorder, autism spectrum disorder, motor inhibition, stop-signal task, serotonin, selective serotonin reuptake inhibitors, inferior frontal cortex, orbitofrontal cortex, basal ganglia, boys, comorbidities
MeSH terms: Autism Spectrum Disorder, Adolescent, Attention Deficit Disorder with Hyperactivity, Basal Ganglia, Child, Double-Blind Method, Fluoxetine, Frontal Lobe, Humans, Inhibition, Psychological, Intelligence, Magnetic Resonance Imaging, Male, Movement, Psychomotor Performance, Prefrontal Cortex, Antidepressive Agents, Second-Generation

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Inverse fluoxetine effects on inhibitory brain activation in non-comorbid boys with ADHD and with ASD

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