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Serotonin and Restricted, Repetitive and Stereotyped Behaviors in Autism

Thursday, 2 May 2013: 09:00-13:00
Banquet Hall (Kursaal Centre)
E. Daly1, C. Ecker1, C. M. Murphy1, N. Gillan1, M. Gudbrandsen1, V. D'Almeida2, D. M. Robertson3 and D. G. Murphy4, (1)Department of Forensic and Neurodevelopmental Sciences, King's College London, Institute of Psychiatry, London, United Kingdom, (2)Centre For Neuroimaging Sciences, Institute of Psychiatry, King's College London, London, United Kingdom, (3)Behavioural Genetics Clinic, South London and Maudsley NHS Foundation Trust, London, United Kingdom, (4)Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, King's College London, London, United Kingdom
Background: People with autism have life-long difficulties in social interaction communication and repetitive behaviours. It has been suggested that the restricted, repetitive and stereotyped behaviors, 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.

Objectives: In order to assess the modifying role of serotonin on inhibitory brain function in adults with autism and controls we employed acute tryptophan depletion (ATD) and functional Magnetic Resonance Imaging (fMRI).

Methods:   We performed a double-blind, placebo-controlled, crossover trial of ATD using fMRI to measure brain activity during a Go/No-Go inhibition task in 14 adults with autism and normal IQ and 14 controls who did not differ in gender, age and IQ.

Results:   During 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 ATD in each group.  Within autistic individuals ATD 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, within people with autism, there was a significant relationship between severity of restricted, repetitive and stereotyped behaviors and functional abnormality at baseline within frontal and thalamic regions; and between the degree that this abnormality was reversible by serotonergic modulation.

Conclusions:   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 restricted, repetitive and stereotyped behaviors in autism and/or provide a novel (tractable) treatment target.

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