Original articleLack of Evidence for Association of the Serotonin Transporter Gene SLC6A4 with Autism
Section snippets
Subjects and Subsets of Autism Families
A total of 352 families were either recruited by the Seaver Autism Research Center (SARC)/Greater New York Autism Research Center for Excellence/STAART Center at Mount Sinai (n = 57), corecruited by the SARC and the Autism Genetic Resource Exchange (AGRE) (n = 130), or obtained from AGRE (n = 165) (Geschwind et al 2001). All parents provided written informed consent. The Autism Diagnostic Interview—Revised (ADI-R) was used for the clinical assessment of affected subjects. Individuals with
No Linkage Between Markers of SLC6A4 and Autism
The 5-HTTLPR locus and 9 SNPs that cover the 5′ half of SLC6A4 gene, including five SNPs previously shown to be positive, were genotyped in 352 families (Figure 1). Accuracy of genotyping has been estimated to > 99.99% by checking 120 individuals in duplicates or triplicates and 27 pairs of monozygote twins. Markers were confirmed to be in Hardy–Weinberg equilibrium and their allelic frequencies and heterozygosity rates were similar to those reported in the NCBI SNP database and in
Discussion
Autism appears to be one of the most highly genetic of the neuropsychiatric disorders. We examined the 5-HT transporter, SLC6A4, in a large cohort of autism families and according to specific endophenotype subsets.
We analyzed the promoter 5-HTTLPR insertion–deletion polymorphisms and nine SNPs within the SLC6A4 gene to evaluate whether these polymorphisms were associated with autism or with certain symptom domains. No significant overtransmission for the S or L allele of 5-HTTLPR was found, nor
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The influence of 5-HTTLPR transporter genotype on amygdala-subgenual anterior cingulate cortex connectivity in autism spectrum disorder
2017, Developmental Cognitive NeuroscienceCitation Excerpt :TD individuals who are carriers of 5-HTTLPR short (S) alleles exhibit increased anxiety related traits (Canli and Lesch, 2007), depressive symptoms (Caspi et al., 2003), as well decreased functional connectivity between the amygdala and the sACC when looking at fearful faces (Pezawas et al., 2005). Whereas studies have found inconclusive evidence of an association between 5-HTTLPR and susceptibility to ASD (e.g. Cook and Leventhal, 1996; Devlin et al., 2005; Zhong et al., 1999; Ramoz et al., 2006), various reports highlight the effect of genotype on the severity of social dysfunction in ASD, which may be related to amygdala functioning and its connectivity with the sACC. For example, Tordjman et al. (2001) found evidence of increased severity in the Combined Social and Communication domain subset of the Autism Diagnostic Interview- Revised (ADI-R; Lord et al., 1994) in participants with the S allele compared to those homozygous for the L allele.
Effects of developmental hyperserotonemia on the morphology of rat dentate nuclear neurons
2016, NeuroscienceCitation Excerpt :Furthermore, abnormalities in basic motor control (Vilensky et al., 1981; Hughes, 1996; Ghaziuddin and Butler, 1998; Teitelbaum et al., 1998; Noterdaeme et al., 2002), skilled motor gestures (DeMeyer et al., 1972; Williams et al., 1980; Jones and Prior, 1985; Ohta et al., 1987; Smith and Bryson, 1994; Rogers et al., 1996; Mostofsky et al., 2006), and motor learning (Mostofsky et al., 2000; Rinehart et al., 2001), are common in ASD and have been attributed to a possible defect in the pre- and postnatal development of specific neural networks including a fronto-cerebello-thalamo-frontal pathway (Mostofsky et al., 2000; Coutinho et al., 2007). The most consistent neurochemical finding reported in ASD is an observed 40–70% increase in platelet serotonin (5-hydroxytriptamine, 5-HT) (Veenstra-VanderWeele et al., 2002; Janusonis, 2005; Ramoz et al., 2006; Coutinho et al., 2007; McNamara et al., 2008; Azmitia et al., 2011), occurring in as many as 30% of autistic subjects and possibly implicated in the pathophysiology of ASD (Azmitia et al., 2011). Serotonin plays an active role in brain development, by promoting dendritic elaboration (Faber and Haring, 1999; Mazer et al., 1997; Yan et al., 1997; Kondoh et al., 2004), synaptogenesis (Okado et al., 1993), neurogenesis (Lauder et al., 1981, 1983), cortical organization (Bennett-Clarke et al., 1994; Cases et al., 1996; Janusonis et al., 2004) and autoregulation of the serotonergic system (Whitaker-Azmitia, 2001).
Serotonin mediated immunoregulation and neural functions: Complicity in the aetiology of autism spectrum disorders
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