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      Developmental changes in brain serotonin synthesis capacity in autistic and nonautistic children.

      Annals of Neurology

      Tomography, Emission-Computed, Age Distribution, Autistic Disorder, psychology, radionuclide imaging, Brain, Child, Adolescent, Child Behavior, Child, Preschool, Female, Humans, Male, Serotonin, biosynthesis

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          Abstract

          Serotonin content, serotonin uptake sites, and serotonin receptor binding measured in animal studies are all higher in the developing brain, compared with adult values, and decline before puberty. Furthermore, a disruption of synaptic connectivity in sensory cortical regions can result from experimental increase or decrease of brain serotonin before puberty. The purpose of the present study was to determine whether brain serotonin synthesis capacity is higher in children than in adults and whether there are differences in serotonin synthesis capacity between autistic and nonautistic children. Serotonin synthesis capacity was measured in autistic and nonautistic children at different ages, using alpha[11C]methyl-L-tryptophan and positron emission tomography. Global brain values for serotonin synthesis capacity (K complex) were obtained for autistic children (n = 30), their nonautistic siblings (n = 8), and epileptic children without autism (n = 16). K-complex values were plotted according to age and fitted to linear and five-parameter functions, to determine developmental changes and differences in serotonin synthesis between groups. For nonautistic children, serotonin synthesis capacity was more than 200% of adult values until the age of 5 years and then declined toward adult values. Serotonin synthesis capacity values declined at an earlier age in girls than in boys. In autistic children, serotonin synthesis capacity increased gradually between the ages of 2 years and 15 years to values 1.5 times adult normal values and showed no sex difference. Significant differences were detected between the autistic and epileptic groups and between the autistic and sibling groups for the change with age in the serotonin synthesis capacity. These data suggest that humans undergo a period of high brain serotonin synthesis capacity during childhood, and that this developmental process is disrupted in autistic children.

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          Most cited references 42

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          Autism Diagnostic Interview-Revised: A revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders

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            Positron emission tomography study of human brain functional development.

            From over 100 children studied with 2-deoxy-2[18F]fluoro-D-glucose and positron emission tomography we selected 29 children (aged 5 days to 15.1 years) who had suffered transient neurological events not significantly affecting normal neurodevelopment. These 29 children were reasonably representative of normal children and provided an otherwise unobtainable population in which to study developmental changes in local cerebral metabolic rates for glucose (lCMRGlc). In infants less than 5 weeks old lCMRGlc was highest in sensorimotor cortex, thalamus, brainstem, and cerebellar vermis. By 3 months, lCMRGlc had increased in parietal, temporal, and occipital cortices; basal ganglia; and cerebellar cortex. Frontal and dorsolateral occipital cortical regions displayed a maturational rise in lCMRGlc by approximately 6 to 8 months. Absolute values of lCMRGlc for various grey matter regions were low at birth (13 to 25 mumol/min/100 gm), and rapidly rose to reach adult values (19 to 33 mumol/min/100 gm) by 2 years. lCMRGlc continued to rise until, by 3 to 4 years, it reached values of 49 to 65 mumol/min/100 gm in most regions. These high rates were maintained until approximately 9 years, when they began to decline, and reached adult rates again by the latter part of the second decade. The highest increases of lCMRGlc over adult values occurred in cerebral cortical structures; lesser increases were seen in subcortical structures and in the cerebellum. This time course of lCMRGlc changes matches that describing the process of initial overproduction and subsequent elimination of excessive neurons, synapses, and dendritic spines known to occur in the developing brain. The determination of changing metabolic patterns accompanying normal brain development is a necessary prelude to the study of abnormal brain development with positron emission tomography.
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              Histoanatomic observations of the brain in early infantile autism.

              Early infantile autism is a behaviorally defined syndrome that is often associated with abnormalities on neurologic examination and seizures. We report on the brain of a 29-year-old autistic man as compared with that of an age- and sex-matched normal control, using gapless sections of whole brain. Abnormalities were found in the hippocampus, subiculum, entorhinal cortex, septal nuclei, mamillary body, selected nuclei of the amygdala, neocerebellar cortex, roof nuclei of the cerebellum, and inferior olivary nucleus.
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                10072042

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