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


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.
    Autism Research 07/2015; DOI:10.1002/aur.1519 · 4.33 Impact Factor
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    • "Nakamura et al. [92] used PET imaging and found reduced 5-HT transporter (5-HTT) binding in the anterior and posterior cingulate cortices associated with impairment in social cognition in individuals with high functioning autism and reduction of 5-HTT binding in the thalamus correlated to obsessive behaviors and interests. Goldberg et al. [93] published findings from a PET imaging study on the parents of children with Autism Spectrum Disorders (ASD) having significantly reduced 5-HT2 binding and found that their platelet 5-HT levels were inversely correlated to the 5-HT2 binding potential. "
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    ABSTRACT: Autism is a behaviorally defined neurodevelopmental disorder that affects over 1% of new births in the United States and about 2% of boys. The etiologies are unknown and they are genetically complex. There may be epigenetic effects, environmental influences, and other factors that contribute to the mechanisms and affected neural pathway(s). The underlying neuropathology of the disorder has been evolving in the literature to include specific brain areas in the cerebellum, limbic system, and cortex. Part(s) of structures appear to be affected most rather than the entire structure, for example, select nuclei of the amygdala, the fusiform face area, and so forth. Altered cortical organization characterized by more frequent and narrower minicolumns and early overgrowth of the frontal portion of the brain, affects connectivity. Abnormalities include cytoarchitectonic laminar differences, excess white matter neurons, decreased numbers of GABAergic cerebellar Purkinje cells, and other events that can be traced developmentally and cause anomalies in circuitry. Problems with neurotransmission are evident by recent receptor and binding site studies especially in the inhibitory GABA system likely contributing to an imbalance of excitatory/inhibitory transmission. As postmortem findings are related to core behavior symptoms, and technology improves, researchers are gaining a much better perspective of contributing factors to the disorder.
    12/2012; 2012(6):703675. DOI:10.6064/2012/703675
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    • "In addition, studies with single-photon emission computed tomography (SPECT) have revealed the low binding capacity of the serotonin transporter in the medial frontal cortex, midbrain, and temporal lobe areas [63], whereas PET and SPECT investigations have determined the reduced binding capacity of the cortical serotonin type 2-receptor in individuals with PDDs, as well as parents of children with autism [43,71]. The low binding potentials have been attributed to the diminished serotonergic nerve terminals and sparse synapse density. "
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    ABSTRACT: Autism is a severe childhood disorder already presenting in the first 3 years of life and, therefore, strongly correlated with neurodevelopmental alterations in prenatal, as well as postnatal period. Neurotransmitters hold a pivotal role in development by providing the stimulation needed for synapses and neuronal networks to be formed during the critical period of neuroplasticity. Aberrations of the serotonergic system modify key processes in the developing brain and are strongly implicated in the pathophysiology of developmental disorders. Evidence for the role of serotonin in autism emerges from neuropathological, imaging and genetic studies. Due to its developmental arrest, autism requires early intervention that would, among others, target the disrupted serotonergic system and utilize brain plasticity to elicit clinically important brain changes in children.
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