Cortical Serotonin 5-HT 2A Receptor Binding and Social Communication in Adults With Asperger’s Syndrome: An in Vivo SPECT Study

VU University Amsterdam, Amsterdamo, North Holland, Netherlands
American Journal of Psychiatry (Impact Factor: 12.3). 06/2006; 163(5):934-6. DOI: 10.1176/appi.ajp.163.5.934
Source: PubMed


The cause of autistic spectrum disorder (i.e., autism and Asperger's syndrome) is unknown. The serotonergic (5-HT) system may be especially implicated. However, cortical 5-HT2A receptor density in adults with the disorder has not been examined, to the authors' knowledge.
The authors investigated cortical 5-HT2A receptor binding in eight adults with Asperger's syndrome and in 10 healthy comparison subjects with single photon emission computed tomography and the selective 5-HT2A receptor ligand 123I iodinated 4-amino-N-[1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]-5-iodo-2-methoxybenzamide (123I-5-I-R91150).
People with Asperger's syndrome had a significant reduction in cortical 5-HT2A receptor binding in the total, anterior, and posterior cingulate; bilaterally in the frontal and superior temporal lobes; and in the left parietal lobe. Also, reduced receptor binding was significantly related to abnormal social communication.
The authors' findings suggest that adults with Asperger's syndrome have abnormalities in cortical 5-HT2A receptor density and that this deficit may underlie some clinical symptoms.

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Available from: Jos L H Eersels, Nov 26, 2015
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    • "les were more likely to have communication problems , an autistic - like trait . Further analysis showed that the genotype effect on communication is mediated by individuals ' perspective taking abilities . Previous studies have demonstrated that the reduced availability of HTR2A impairs empathy - related behaviors , such as social communication ( Murphy et al . , 2006 ) and prosocial and affiliated orientations ( Gerretsen et al . , 2010 ) ."
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    ABSTRACT: Previous studies have indicated that empathic traits, such as perspective taking, are associated with the levels of serotonin in the brain and with autism spectrum conditions. Inspired by the finding that the serotonin receptor 2A gene (HTR2A) modulates the availability of serotonin, this study investigated to what extent HTR2A modulates individuals' perspective taking ability and autistic-like traits. To examine the associations of the functional HTR2A polymorphism T102C (rs6313) with individuals' perspective taking abilities and autistic-like traits, we differentiated individuals according to this polymorphism and measured empathic and autistic-like traits with Interpersonal Reactivity Index (IRI) and Autism-Spectrum Quotient (AQ) scale in 523 Chinese people. The results indicated that this polymorphism was significantly associated with the scores on Perspective Taking and Personal Distress subscales of IRI, and Communication subscale of AQ. Individuals with a greater number of the C alleles were less likely to spontaneously adopt the point of view of others, more likely to be anxious when observing the pain endured by others, and more likely to have communication problems. Moreover, the genotype effect on communication problems was mediated by individuals' perspective taking ability. These findings provide evidence that the HTR2A T102C polymorphism is a predictor of individual differences in empathic and autistic-like traits and highlight the role of the gene in the connection between perspective taking and autistic-like traits.
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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.
    No preview · Article · Jul 2015 · Autism Research
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    • "Alterations in brain 5-HT receptor density were found in autistic patients. A reduction of 5-HT2A binding sites in the cingulate, frontal, and temporal cortex was detected in adults with Asperger syndrome by single photon emission computed tomography (SPECT; Murphy et al., 2006), although a later PET study found contrasting results (Girgis et al., 2011). A reduced density of 5-HT1A and 5-HT2 receptors in posterior cingulate cortex and fusiform cortex, brain regions involved in social and emotional behaviors, was observed in post-mortem brain tissue from young adults diagnosed with autism other than Asperger syndrome (Oblak et al., 2013). "
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    ABSTRACT: Serotonin type 7 receptors (5-HT7) are expressed in several brain areas, regulate brain development, synaptic transmission and plasticity, and therefore are involved in various brain functions such as learning and memory. A number of studies suggest that 5-HT7 receptors could be potential pharmacotherapeutic target for cognitive disorders. Several abnormalities of serotonergic system have been described in patients with autism spectrum disorder (ASD), including abnormal activity of 5-HT transporter, altered blood and brain 5-HT levels, reduced 5-HT synthesis and altered expression of 5-HT receptors in the brain. A specific role for 5-HT7 receptors in ASD has not yet been demonstrated but some evidence implicates their possible involvement. We have recently shown that 5-HT7 receptor activation rescues hippocampal synaptic plasticity in a mouse model of Fragile X Syndrome, a monogenic cause of autism. Several other studies have shown that 5-HT7 receptors modulate behavioral flexibility, exploratory behavior, mood disorders and epilepsy, which include core and co-morbid symptoms of ASD. These findings further suggest an involvement of 5-HT7 receptors in ASD. Here, we review the physiological roles of 5-HT7 receptors and their implications in Fragile X Syndrome and other ASD.
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