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Autism and the serotonin transporter: the long and short of it.

Abstract：

:Autism is a neurodevelopmental disorder manifesting early in childhood. Some symptoms of autism are alleviated by treatment with selective serotonin reuptake inhibitors, which are known to interact with the serotonin transporter. Moreover, variation in the gene that encodes the transporter (SLC6A4), especially the HTTLPR locus, is known to modulate its expression. It is natural, therefore, to evaluate whether this variation plays a role in liability to autism. We investigated the impact of alleles at HTTLPR and three other loci in SLC6A4 by using a large, independent family-based sample (390 families, 1528 individuals) from the NIH Collaborative Programs of Excellence in Autism (CPEA) network. Allele transmissions to individuals diagnosed with autism were biased only for HTTLPR, both for the narrow diagnosis of autism (P=0.035) and for the broader diagnosis of autism spectrum (P=0.007). The short allele of HTTLPR was significantly overtransmitted. Investigation of haplotype transmissions suggested that, in our data, biased transmission was only due to HTTLPR. With respect to this locus, there are now seven of 12 studies reporting significant transmission bias of HTTLPR alleles, a noteworthy result in itself. However, the studies with significant findings are almost equally divided between overtransmission of short and overtransmission of long alleles. We place our results within this extremely heterogeneous field of studies. Determining the factors influencing the relationship between autism phenotypes and HTTLPR variation, as well as other loci in SLC6A4, could be an important advance in our understanding of this complex disorder.

journal_name

Mol Psychiatry

journal_title

Molecular psychiatry

authors

Devlin B,Cook EH Jr,Coon H,Dawson G,Grigorenko EL,McMahon W,Minshew N,Pauls D,Smith M,Spence MA,Rodier PM,Stodgell C,Schellenberg GD,CPEA Genetics Network.

doi

10.1038/sj.mp.4001724

subject

Has Abstract

pub_date

2005-12-01 00:00:00

pages

1110-6

issue

12

eissn

1359-4184

issn

1476-5578

pii

4001724

journal_volume

10

pub_type

临床试验,杂志文章,多中心研究

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