BRAIN SEROTONIN SYNTHESIS IN AUTISM

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Autism is a devastating neurodevelopmental disorder characterized by a spectrum of abnormal behaviors including profound impairment in social interaction and communication, restrictive repetitive and stereotyped patterns of behavior, interests, and activities, as well as stereotypic motor abnormalities. Studies investigating alterations of neuro- transmitters in blood of autistic patients have consistently found increased platelet serotonin in approximately one-third to one-half of autistic patients. Studies of the serotonin metabolite 5-HIAA in cerebrospinal fluid, however, have failed to demonstrate consistent abnormalities of central serotonergic tone. Previously, no method for direct in vivo measurement of serotonin synthesis in humans was available, and only indirect and relatively insensitive measures could be made. Alpha[C-11]-Methyl-L-tryptophan has been developed as a tracer for serotonin synthesis with positron emission tomography (PET) and now allows a direct in vivo measurement of serotonin synthesis in humans. Using this technique, we have preliminary data demonstrating alteration in the whole brain serotonin synthesis in autistic children, as compared to their siblings aged 8-14 years or children with epilepsy aged 2-12 years. Furthermore, we have found focal differences between autistic boys and their siblings. Asymmetries of serotonin synthesis in frontal cortex, thalamus and cerebellum were found in autistic boys, but not in autistic girls nor in the majority of siblings studied. We propose that abnormal serotonin synthesis plays a role in the pathophysiology of autism. In order to further characterize whole brain and focal abnormalities of serotonin synthesis in autistic children, we propose to use alpha[C-11]-Methyl-L-tryptophan imaged with PET to: 1. Determine whether autistic children differ from their siblings with expanded phenotype of autistic disorder, their normal siblings and epileptic children with regard to changes in values for whole brain serotonin synthesis capacity with age. 2. Determine whether there are abnormalities of serotonin synthesis in specific brain regions in autistic children. An understanding of the neurochemical disturbances in autism is important for the development of new treatment approaches.