title: Response inhibition and serotonin in autism: a functional MRI study using acute tryptophan depletion.
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.
authors: 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.
authors: Eileen
authors: E
authors: Daly
authors: 1 Sackler Institute of Translational Neurodevelopment, Department of Forensic and Neurodevelopmental Science, Institute of Psychiatry, King's College London, UK.
authors: Christine
authors: C
authors: Ecker
authors: 2 Department of Psychiatry, National University of Ireland, Galway, Ireland.
authors: Brian
authors: B
authors: Hallahan
authors: 1 Sackler Institute of Translational Neurodevelopment, Department of Forensic and Neurodevelopmental Science, Institute of Psychiatry, King's College London, UK.
authors: Quinton
authors: Q
authors: Deeley
authors: 1 Sackler Institute of Translational Neurodevelopment, Department of Forensic and Neurodevelopmental Science, Institute of Psychiatry, King's College London, UK.
authors: Michael
authors: M
authors: Craig
authors: 1 Sackler Institute of Translational Neurodevelopment, Department of Forensic and Neurodevelopmental Science, Institute of Psychiatry, King's College London, UK.
authors: Clodagh
authors: C
authors: Murphy
authors: 1 Sackler Institute of Translational Neurodevelopment, Department of Forensic and Neurodevelopmental Science, Institute of Psychiatry, King's College London, UK.
authors: Patrick
authors: P
authors: Johnston
authors: 1 Sackler Institute of Translational Neurodevelopment, Department of Forensic and Neurodevelopmental Science, Institute of Psychiatry, King's College London, UK.
authors: Debbie
authors: D
authors: Spain
authors: 1 Sackler Institute of Translational Neurodevelopment, Department of Forensic and Neurodevelopmental Science, Institute of Psychiatry, King's College London, UK.
authors: Nicola
authors: N
authors: Gillan
authors: 1 Sackler Institute of Translational Neurodevelopment, Department of Forensic and Neurodevelopmental Science, Institute of Psychiatry, King's College London, UK.
authors: Maria
authors: M
authors: Gudbrandsen
authors: 3 Department of Neuroimaging, Institute of Psychiatry, King's College London, UK.
authors: Michael
authors: M
authors: Brammer
authors: 3 Department of Neuroimaging, Institute of Psychiatry, King's College London, UK.
authors: Vincent
authors: V
authors: Giampietro
authors: 4 Department of Psychiatry, University of Illinois at Chicago, USA.
authors: Melissa
authors: M
authors: Lamar
authors: 5 Sussex Partnership NHS Foundation Trust, Brighton and Sussex Medical School, Brighton, UK.
authors: Lisa
authors: L
authors: Page
authors: 1 Sackler Institute of Translational Neurodevelopment, Department of Forensic and Neurodevelopmental Science, Institute of Psychiatry, King's College London, UK.
authors: Fiona
authors: F
authors: Toal
authors: 6 Dementia Research Unit, Institute of Neurology, University College London, UK.
authors: Nicole
authors: N
authors: Schmitz
authors: 7 Department of Psychological Medicine, Institute of Psychiatry, King's College London, UK.
authors: Anthony
authors: A
authors: Cleare
authors: 8 Behavioural and Developmental Clinical Academic Group, South London and Maudsley NHS Foundation.
authors: Dene
authors: D
authors: Robertson
authors: 9 Department of Child and Adolescent Psychiatry, Institute of Psychiatry, King's College London, UK.
authors: Katya
authors: K
authors: Rubia
authors: 1 Sackler Institute of Translational Neurodevelopment, Department of Forensic and Neurodevelopmental Science, Institute of Psychiatry, King's College London, UK.
authors: Declan G M
authors: DG
authors: Murphy
mesh_terms: D000293:Adolescent; D000328:Adult; D001321:Autistic Disorder / Q000175:diagnosis / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009433:Neural Inhibition / Q000502:physiology; D010775:Photic Stimulation / Q000379:methods; D011930:Reaction Time / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism*; D014364:Tryptophan / Q000378:metabolism*; D055815:Young Adult
chemical_list: D012701:Serotonin; D014364:Tryptophan
keywords: autistic spectrum disorder; impulsivity and inhibition disorders