-------------------------------- Serotonin Yonan: Genetic dissection of autism spectrum disorder http://gradworks.umi.com/31/74/3174930.html Genetic dissection of autism spectrum disorder by Yonan, Amanda Lynne, PhD, COLUMBIA UNIVERSITY, 2005, 360 pages; 3174930 Abstract: Autistic Disorder (OMIM 209850) is a neuropsychiatric developmental disorder characterized by severe disabilities in three distinct areas: (1) social interaction, (2) communication, and (3) restricted and repetitive behaviors or interests. Evidence from twin and epidemiological studies clearly establishes autism as a genetic disorder, although no Mendelian inheritance pattern has been easily identified. In fact, all evidence points to autism being a complex disorder, resulting from the combination of multiple genetic and environmental factors. This thesis describes our efforts to identify the genetic factors involved in autism and Autism Spectrum Disorders (ASD). While controlling for genetic heterogeneity as much as possible in our study design, we undertook a genetic analysis of the largest sample of ASD families ever collected. Using new techniques in bioinformatics, and by subdividing the population based on a prior hypothesis, we were able to narrow down the genomic regions involved in ASD to one significantly linked region on chromosome 17q11. We identified and characterized a candidate gene in 17q11, the serotonin transporter (SLC6A4); previously identified as a candidate gene to ASD from many different avenues, including autistic's response to SSRI's and positive association studies. We examined SLC6A4's genetic involvement in our large sample of ASD families. This thesis provides new analysis on the genomic regions involved in ASD, describes new methodologies for genotyping and genetic analysis as well as outlining the effect of one specific candidate gene on ASD. ------------------------- Serotonin ITGB3 autism and serotonin http://www.nature.com/ejhg/journal/v14/n8/abs/5201644a.html Autism is a pervasive developmental disorder affecting more males than females. Heritability estimates for autism can rise above 90%, and genes influencing the serotonin system are strong candidates for autism susceptibility genes, as drugs selectively acting on the serotonin system are some of the most effective treatments for maladaptive behaviors seen in autism. ITGB3 was recently identified as a male quantitative trait locus (QTL) for whole-blood serotonin levels in the Hutterites (P=0.0003). Here, we demonstrate associations between variation in ITGB3 and serotonin levels in two outbred samples (P=0.010 and 0.015). Lastly, we show that a coding variant of ITGB3 is associated with autism susceptibility in a large multiplex sample (P=0.00082), and that this variation has different effects in males and females (P=0.0018). Genetics of autism spectrum disorder http://www.nature.com/ejhg/journal/v14/n6/abs/5201610a.html ----------------------------- http://www.springerlink.com/content/1573-3432/ vol 36, number 5, page 697 plus Published online: 13 April 2006 Abstract One of the most consistent biological findings in autism is elevated whole blood serotonin (5-HT) levels found in about 1/3 of cases. Immune abnormalities are also commonly observed in this disorder. Given 5-HT�s role as an immunomodulator, possible connections between 5-HT and immune abnormalities in autism are explored in this review. Areas of focus include hyperserotoninemia and cellular immune function, autoantibodies to 5-HT receptors, and 5-HT�s role in autoimmunity. Further research is needed to determine the interactions between neuropsychiatric and immune dysfunction in autism and related disorders. pdf'd and printed http://www.springerlink.com/content/x06l575373t3410r/?p=cb21fb73e85e41e596ba9616b6452038&pi=12