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Response inhibition and serotonin in autism: a functional MRI study using acute tryptophan depletion
It has been suggested that the restricted, stereotyped and repetitive behaviours typically found in autism are underpinned by deficits of inhibitory control. The biological basis of this is unknown but may include differences in the modulatory role of neurotransmitters, such as serotonin, which are...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4132649/ https://www.ncbi.nlm.nih.gov/pubmed/25070512 http://dx.doi.org/10.1093/brain/awu178 |
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author | Daly, Eileen Ecker, Christine Hallahan, Brian Deeley, Quinton Craig, Michael Murphy, Clodagh Johnston, Patrick Spain, Debbie Gillan, Nicola Gudbrandsen, Maria Brammer, Michael Giampietro, Vincent Lamar, Melissa Page, Lisa Toal, Fiona Schmitz, Nicole Cleare, Anthony Robertson, Dene Rubia, Katya Murphy, Declan G. M. |
author_facet | Daly, Eileen Ecker, Christine Hallahan, Brian Deeley, Quinton Craig, Michael Murphy, Clodagh Johnston, Patrick Spain, Debbie Gillan, Nicola Gudbrandsen, Maria Brammer, Michael Giampietro, Vincent Lamar, Melissa Page, Lisa Toal, Fiona Schmitz, Nicole Cleare, Anthony Robertson, Dene Rubia, Katya Murphy, Declan G. M. |
author_sort | Daly, Eileen |
collection | PubMed |
description | It has been suggested that the restricted, stereotyped and repetitive behaviours typically found in autism are underpinned by deficits of inhibitory control. The biological basis of this is unknown but may include differences in the modulatory role of neurotransmitters, such as serotonin, which are implicated in the condition. However, this has never been tested directly. We therefore assessed the modifying role of serotonin on inhibitory brain function during a Go/No-Go task in 14 adults with autism and normal intelligence and 14 control subjects that did not differ in gender, age and intelligence. We undertook a double-blind, placebo-controlled, crossover trial of acute tryptophan depletion using functional magnetic resonance imaging. Following sham, adults with autism relative to controls had reduced activation in key inhibitory regions of inferior frontal cortex and thalamus, but increased activation of caudate and cerebellum. However, brain activation was modulated in opposite ways by depletion in each group. Within autistic individuals depletion upregulated fronto-thalamic activations and downregulated striato-cerebellar activations toward control sham levels, completely ‘normalizing’ the fronto-cerebellar dysfunctions. The opposite pattern occurred in controls. Moreover, the severity of autism was related to the degree of differential modulation by depletion within frontal, striatal and thalamic regions. Our findings demonstrate that individuals with autism have abnormal inhibitory networks, and that serotonin has a differential, opposite, effect on them in adults with and without autism. Together these factors may partially explain the severity of autistic behaviours and/or provide a novel (tractable) treatment target. |
format | Online Article Text |
id | pubmed-4132649 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-41326492014-08-18 Response inhibition and serotonin in autism: a functional MRI study using acute tryptophan depletion Daly, Eileen Ecker, Christine Hallahan, Brian Deeley, Quinton Craig, Michael Murphy, Clodagh Johnston, Patrick Spain, Debbie Gillan, Nicola Gudbrandsen, Maria Brammer, Michael Giampietro, Vincent Lamar, Melissa Page, Lisa Toal, Fiona Schmitz, Nicole Cleare, Anthony Robertson, Dene Rubia, Katya Murphy, Declan G. M. Brain Original Articles It has been suggested that the restricted, stereotyped and repetitive behaviours typically found in autism are underpinned by deficits of inhibitory control. The biological basis of this is unknown but may include differences in the modulatory role of neurotransmitters, such as serotonin, which are implicated in the condition. However, this has never been tested directly. We therefore assessed the modifying role of serotonin on inhibitory brain function during a Go/No-Go task in 14 adults with autism and normal intelligence and 14 control subjects that did not differ in gender, age and intelligence. We undertook a double-blind, placebo-controlled, crossover trial of acute tryptophan depletion using functional magnetic resonance imaging. Following sham, adults with autism relative to controls had reduced activation in key inhibitory regions of inferior frontal cortex and thalamus, but increased activation of caudate and cerebellum. However, brain activation was modulated in opposite ways by depletion in each group. Within autistic individuals depletion upregulated fronto-thalamic activations and downregulated striato-cerebellar activations toward control sham levels, completely ‘normalizing’ the fronto-cerebellar dysfunctions. The opposite pattern occurred in controls. Moreover, the severity of autism was related to the degree of differential modulation by depletion within frontal, striatal and thalamic regions. Our findings demonstrate that individuals with autism have abnormal inhibitory networks, and that serotonin has a differential, opposite, effect on them in adults with and without autism. Together these factors may partially explain the severity of autistic behaviours and/or provide a novel (tractable) treatment target. Oxford University Press 2014-09 2014-07-27 /pmc/articles/PMC4132649/ /pubmed/25070512 http://dx.doi.org/10.1093/brain/awu178 Text en © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Original Articles Daly, Eileen Ecker, Christine Hallahan, Brian Deeley, Quinton Craig, Michael Murphy, Clodagh Johnston, Patrick Spain, Debbie Gillan, Nicola Gudbrandsen, Maria Brammer, Michael Giampietro, Vincent Lamar, Melissa Page, Lisa Toal, Fiona Schmitz, Nicole Cleare, Anthony Robertson, Dene Rubia, Katya Murphy, Declan G. M. Response inhibition and serotonin in autism: a functional MRI study using acute tryptophan depletion |
title | Response inhibition and serotonin in autism: a functional MRI study using acute tryptophan depletion |
title_full | Response inhibition and serotonin in autism: a functional MRI study using acute tryptophan depletion |
title_fullStr | Response inhibition and serotonin in autism: a functional MRI study using acute tryptophan depletion |
title_full_unstemmed | Response inhibition and serotonin in autism: a functional MRI study using acute tryptophan depletion |
title_short | Response inhibition and serotonin in autism: a functional MRI study using acute tryptophan depletion |
title_sort | response inhibition and serotonin in autism: a functional mri study using acute tryptophan depletion |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4132649/ https://www.ncbi.nlm.nih.gov/pubmed/25070512 http://dx.doi.org/10.1093/brain/awu178 |
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