The hypothesis of this proposal is that the familial hyperserotoninemia present in a group of children with a diagnosis of infantile autism and in their family members plays a role in the development of the spectrum of features found in those families, including 1) abnormal immune response in autistic children and family members, 2) pre-, peri-, and postnatal complications of pregnancy in mothers of autistic children, and 3) an increased incidence of developmental delay and learning disabilities in other family members. To test this hypothesis, four groups of families will be studied: High serotonin: 1. caucasian families, 2. black families; normal serotonin: 1. caucasian families, 2. black families. A total of 75 autistic probands and 225 family members will be enrolled in the study. A low dropout rate is anticipated. All study participants will receive cognitive testing and donate blood samples. Cognitive testing will be completed prior to obtaining blood samples. Blood samples will be drawn and tested for: 1) serotonin levels and platelet uptake studies; 2) cellular immunology profiles including T cell, B cell, interleukin-2, OkDr cell, and cell surface receptors; 3) HLA, B, C, Dr, and autocrossmatch for autoantibodies; and 4) chromosomal fragile site determination in autistic probands and if positive, in first degree family members. In addition, the following data will be collected on each adult entering the study: 1) comprehensive genetic family history, including systematic pedigrees, medical, social, and educational history of the proband's family; 2) a structured psychiatric interview, the SADS-L and a family attitude questionnaire, the STAR; and 3) pre-, peri-, and postnatal histories for all pregnancies of mothers with an autistic child and for pregnancies of first-degree family members. Epidemiologic analyses will include descriptive statistics for all data sets, particularly to define normal serotonin levels and platelet studies on black families; analyses of the sources of variance within these data sets; and risk factor evaluation for symptomatology in autistic children and their families. The potential theoretical significance of this study is the provision of a unifying hypothesis to explain relationships among seemingly unrelated sets of symptoms and different sets of symptoms seen in subgroups of children with autism.
| Cuccaro, M L; Wright, H H; Abramson, R K et al. (1993) Whole-blood serotonin and cognitive functioning in autistic individuals and their first-degree relatives. J Neuropsychiatry Clin Neurosci 5:94-101 |
