STAART Network Centers: Mt. Sinai School of Medicine

Genetics (An Autism Susceptibility Gene and Repetitive Behaviors in Autism)
Principal Investigator: Buxbaum; site: Mt. Sinai Medical School

Autism has been shown to be highly heritable, with heritability estimated at over 90%. Estimates for the number of genes underlying autism range from 3 to over 15 and there is evidence for genetic heterogeneity. The evidence for linkage to chromosome 2 was observed in our studies and in additional studies. The current application represents a focused attempt to identify an autism susceptibility gene on 2Q. This study aims to identify an additional 150 families with at least two family members affected with autism, to genotype samples and analyze the data for linkage to autism and repetitive behaviors. In addition, we will look for overlap between areas of linkage for repetitive behaviors and candidate genes of serotonin system.

Specific Aims:

1. Identify an additional 150 families with at least two family members, usually sibs, affected with autism.
2. Genotype samples across the linked regions and analyze the data for linkage to autism.
3. Genotype polymorphisms in genes of interest across linked regions and carry out association studies.
4. Genotype polymorphisms in serotonin-related genes and carry out association studies.

Neuroimaging (Imaging 5HT Transporters and 5HT 2a Receptors in Aspergers)
Principal Investigator: Laruelle, site: NY State Psychiatric Institute (Columbia)

Several lines of evidence implicate the serotonergic system in the pathophysiology of aspergers. However, very little specific information is currently available regarding 5-HT function in the brain of patients with aspergers. This study aims to quantify the anatomical distribution of two key elements of the 5-HT systems that have been implicated in aspegers: the 5-HT transporter (SERT) and the 5HT2A receptors. Forty adult patients with aspergers and forty controls matched for age, gender and ethnicity will undergo a MRI scan and two PET scans with [11C]DASB and [11c]MDL 100907, respectively. Following the scans, subjects will be treated with fluoxetine in another study. The hypothesis is that patients with aspegers will present reduced density of SERT and a compensatory upregulation of 5HT2A receptors in several areas of the limbic system. In addition, candidate genes of the 5HT2A receptor and the serotonin transporter will be explored in these subjects.

Specific Aims:

1. To study the regional distribution of SERT in 40 adult patients with Asperger's disorder and 40 matched controls, by measuring the binding potential (BP) of [11C]DASB in limbic and neocortical regions. The hypothesis is that Asperger's disorder will be associated with a generalized decrease in [11C]DASB BP, and that this decrease will be more pronounced in the ACC, OFC and AMY.
2. To study the regional distribution of 5-HT2A receptors in the same 40 adult patients with Asperger's disorder and 40 matched controls, by measuring the BP of [11C]MDL 100907 in limbic and neocortical regions. The hypothesis is that Asperger's disorder will be associated with a generalized increase in [11C]MDL 100907 BP, and that this increase will be more pronounced in the ACC, OFC and AMY.
3. To study the relationship between [11C]DASB and [11C]MDL 100907 regional BP in patients with Asperger's disorder and matched controls. The hypothesis is that the upregulation of [11C]MDL 100907 BP will be correlated with the reduction in [11C]DASB BP in patients with Aspergers disorder.
4. To study the relationship between alterations of 5-HT markers and symptom domains in Asperger's disorder.

Citalopram Treatment in Children with Autism Spectrum Disorders and High Levels of Repetitive Behavior
Principal Investigator: Hollander; sites: Mt. Sinai and Long Island Jewish Medical Center
Multi-site study - see description under Social and Affective Processes in Autism
Primary Site: Boston University School of Medicine

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