pyrimidinones and Autistic-Disorder

Rett syndrome (RS) is a neurodevelopmental disorder that shares many symptomatic and pathological commonalities with idiopathic autism. Alterations in protein synthesis-dependent synaptic plasticity (PSDSP) are a hallmark of a number of syndromic forms of autism; in the present work, we explore the consequences of disruption and rescue of PSDSP in a mouse model of RS. We report that expression of a key regulator of synaptic protein synthesis, the metabotropic glutamate receptor 5 (mGlu

Topics: Adult; Allosteric Regulation; Animals; Autistic Disorder; Autopsy; Disease Models, Animal; Female; Gene Expression Regulation; Hippocampus; Humans; Male; Methyl-CpG-Binding Protein 2; Mice; Mice, Knockout; Motor Cortex; Neuronal Plasticity; Pyrazoles; Pyrimidinones; Receptor, Metabotropic Glutamate 5; Rett Syndrome; Seizures; Signal Transduction; Young Adult

The serotonergic system is implicated in disordered emotional behavior. Autism is characterized by impaired processing of emotional information. The serotonergic (5-HT) system is also critically involved in brain development, and abnormal brain synthesis of serotonin is observed in autism. Furthermore, whole blood and platelet serotonin have been reported to be elevated in autism. The authors examined the CNS serotonin system in autism in vivo. 5-HT2 receptors were visualized by PET imaging of [18F]setoperone-binding in this pilot study of 6 high-functioning autistic adults and 10 matched-control participants. Autism subjects had less thalamic [18F]setoperone binding than controls, when covaried for age, but no difference reached significance in other areas. A negative relationship between thalamic binding and history of language impairment was also observed. Further studies will be needed to gain a clearer picture of the role of the 5-HT system in autism.

Topics: Adult; Autistic Disorder; Brain; Case-Control Studies; Female; Fluorine Radioisotopes; Functional Neuroimaging; Humans; Language Disorders; Male; Pilot Projects; Positron-Emission Tomography; Pyrimidinones; Radioligand Assay; Radiopharmaceuticals; Receptors, Serotonin, 5-HT2; Thalamus

Parents (N = 19) of children with autism spectrum disorders (ASD) and adult controls (N = 17) underwent positron emission tomography (PET) using [(18)F]setoperone to image cortical serotonin type-2 (5-HT2) receptors. The 5-HT2 binding potentials (BPs) were calculated by ratioing [(18)F]setoperone intensity in regions of interest (ROI) to cerebellar intensity. Cortical 5-HT2 BPs were significantly lower in parents compared to controls and platelet 5-HT levels were significantly negatively correlated with cortical 5-HT2 BP in parents. Lower cortical 5-HT2 receptor density in parents of children with ASD is consistent with reports of diminished 5-HT2 expression and functioning in individuals with ASD. Further research should examine the relationship of reduced 5-HT2 receptor expression to underlying causation and to clinical and neurochemical correlates of autistic behavior.

Topics: Adult; Autistic Disorder; Cerebral Cortex; Child; Female; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Phenotype; Pyrimidinones; Radionuclide Imaging; Receptors, Serotonin, 5-HT2; Reference Values; Serotonin Antagonists