Article

Cortical Serotonin Type-2 Receptor Density in Parents of Children with Autism Spectrum Disorders

Department of Psychiatry and Behavioral Neurosciences, McMaster University, Hamilton, ON, Canada.
Journal of Autism and Developmental Disorders (Impact Factor: 3.34). 08/2008; 39(1):97-104. DOI: 10.1007/s10803-008-0604-4
Source: PubMed

ABSTRACT 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.

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    • "First, atypical antipsychotics, acting via HTR2A, are known to alleviate repetitive behaviour and aggression in ASD patients [Buitelaar & Willemsen-Swinkels, 2000; Marek, Carpenter, McDougle, & Price, 2003]. Furthermore, ASD subjects or their relatives displayed significant reduction in cortical [Goldberg et al., 2009; Murphy et al., 2006; Oblak, Gibbs, & Blatt, 2013] as well as platelet [Cook et al., 1993; McBride et al., 1989] HTR2A binding. Also, platelet aggregation, an indirect measure of platelet HTR2A activity/number, was found to be reduced in ASD subjects [Hranilovic et al., 2009; McBride et al., 1989; Safai-Kutti, Denfors, Kutti, & Wadenvik, 1988]. "
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    ABSTRACT: Disturbed brain and peripheral serotonin homeostasis is often found in subjects with autism spectrum disorder (ASD). The role of the serotonin receptor 2A (HTR2A) in the regulation of central and peripheral serotonin homeostasis, as well as its altered expression in autistic subjects, have implicated the HTR2A gene as a major candidate for the serotonin disturbance seen in autism. Several studies, yielding so far inconclusive results, have attempted to associate autism with a functional SNP -1438 G/A (rs6311) in the HTR2A promoter region, while possible contribution of epigenetic mechanisms, such as DNA methylation, to HTR2A dysregulation in autism has not yet been investigated. In this study, we compared the mean DNA methylation within the regulatory region of the HTR2A gene between autistic and control subjects. DNA methylation was analysed in peripheral blood leukocytes using bisulfite conversion and sequencing of the HTR2A region containing rs6311 polymorphism. Autistic subjects of rs6311 AG genotype displayed higher mean methylation levels within the analysed region than the corresponding controls (P < 0.05), while there was no statistically significant difference for AA and GG carriers. Our study provides preliminary evidence for increased HTR2A promoter methylation in leukocytes of a portion of adult autistic subjects, indicating that epigenetic mechanisms might contribute to HTR2A dysregulation observed in individuals with ASD. Autism Res 2015. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
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    • "Therefore, extension of studies to ages younger than 24 months may allow study of development of core processes related to social development and allow identification of a marker that predicts later diagnosis of ASD. & Reduced Serotonin 5-HT2 Receptor Binding Density in Parents of Children with ASDs (Goldberg et al., 2008) Serotonin (5-HT) was first shown to have a role in ASD in 1961 when Schain and Freedman (1961) reported elevated serotonin in whole blood in individuals with ASD compared to controls. Subsequent studies have highlighted that serotonin in whole blood is almost exclusively found within platelets. "
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