1. ¹Pritzker School of Medicine, University of Chicago, Chicago, IL, USA
2. ²Laboratory of Developmental Neuroscience, Department of Psychiatry, Institute of Juvenile Research, University of Illinois at Chicago, Chicago, IL, USA
3. ³Department of Psychiatry, University of Florida, Florida, FL, USA
4. ⁴Department of Human Genetics, University of Chicago, Chicago, IL, USA
5. ⁵Departments of Molecular Physiology and Biophysics and Psychiatry, and Center for Molecular Neuroscience, Vanderbilt University Medical Center, Nashville, TN, USA

Correspondence: Dr J Veenstra-VanderWeele, Center for Molecular Neuroscience, Vanderbilt University Medical Center, Medical Research Building III, 465 21st Ave S, Nashville, TN 37232, USA. Tel: +1 615 936-1700; Fax: +1 615 936-3745; E-mail: jVVw@vanderbilt.edu

⁶Current address: Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School and Medical and Population Genetics, Broad Institute of MIT and Harvard, USA.

⁷Current address: Center for Molecular Neuroscience, Vanderbilt University Medical Center, Nashville, TN, USA.

Received 31 October 2006; Revised 26 February 2007; Accepted 27 February 2007; Published online 4 April 2007.

Abstract

Elevated platelet serotonin (5-hydroxytryptamine, 5-HT) is found in a subset of children with autism and in some of their first-degree relatives. Indices of the platelet serotonin system, including whole blood 5-HT, 5-HT binding affinity for the serotonin transporter (K_m), 5-HT uptake (V_max), and lysergic acid diethylamide (LSD) receptor binding, were previously studied in 24 first-degree relatives of probands with autism, half of whom were selected for elevated whole blood 5-HT levels. All subjects were then genotyped for selected polymorphisms at the SLC6A4, HTR7, HTR2A, ITGB3, and TPH1 loci. Previous studies allowed an a priori prediction of SLC6A4 haplotypes that separated the subjects into three groups that showed significantly different 5-HT binding affinity (K_m, p=0.005) and 5-HT uptake rate (V_max, p=0.046). Genotypes at four individual polymorphisms in SLC6A4 were not associated with platelet 5-HT indices. Haplotypes at SLC6A4 and individual genotypes of polymorphisms at SLC6A4, HTR7, HTR2A, ITGB3, and TPH1 showed no significant association with whole blood 5-HT. Haplotype analysis of two polymorphisms in TPH1 revealed a nominally significant association with whole blood 5-HT (p=0.046). These initial studies of indices of the 5-HT system with several single-nucleotide polymorphisms at loci in this system generate hypotheses for testing in other samples.