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Brain. 2014 Sep;137(Pt 9):2600-10. doi: 10.1093/brain/awu178. Epub 2014 Jul 28.

Response inhibition and serotonin in autism: a functional MRI study using acute tryptophan depletion.

Author information

1
1 Sackler Institute of Translational Neurodevelopment, Department of Forensic and Neurodevelopmental Science, Institute of Psychiatry, King's College London, UK eileen.daly@kcl.ac.uk.
2
1 Sackler Institute of Translational Neurodevelopment, Department of Forensic and Neurodevelopmental Science, Institute of Psychiatry, King's College London, UK.
3
2 Department of Psychiatry, National University of Ireland, Galway, Ireland.
4
3 Department of Neuroimaging, Institute of Psychiatry, King's College London, UK.
5
4 Department of Psychiatry, University of Illinois at Chicago, USA.
6
5 Sussex Partnership NHS Foundation Trust, Brighton and Sussex Medical School, Brighton, UK.
7
6 Dementia Research Unit, Institute of Neurology, University College London, UK.
8
7 Department of Psychological Medicine, Institute of Psychiatry, King's College London, UK.
9
8 Behavioural and Developmental Clinical Academic Group, South London and Maudsley NHS Foundation.
10
9 Department of Child and Adolescent Psychiatry, Institute of Psychiatry, King's College London, UK.

Abstract

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.

KEYWORDS:

autistic spectrum disorder; impulsivity and inhibition disorders

PMID:
25070512
PMCID:
PMC4132649
DOI:
10.1093/brain/awu178
[Indexed for MEDLINE]
Free PMC Article

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