Preliminary Results of a Study of the Platelet Dense Granule and Serotonin Storage Pool in Autistic Children and Their Families.

Abstract

4456 The etiology of autism is thought to be neurobiological, but the mechanisms involved are not known. One possible clue into this disorder can be found in multiple clinical studies which have established that at least 30-40% of individuals diagnosed with autism have significantly elevated levels of serotonin (5HT) in their blood. Serotonin transport by platelets and 5HT plasma levels have been found to be altered in patients with multiple neurobiological disorders, including bipolar disorder, schizophrenia, depression, aggression, autism, and migraine headache. Serotonin has numerous functions, including regulation of vasoconstriction, vasodilatation, and coagulation. A review of the literature reveals few studies of coagulopathy related to autism other than attempts to associate vaccination or infections with the etiology of autism. One recent study, of a limited number of individuals with autism spectrum disorders (ASD) and their families, reported a significant incidence of thrombophilia. All children evaluated (10/10) and 15 of 16 family members in the study were found to be at risk for thrombophilia disorders. We have been evaluating patients for PL dysfunction for many years and recently, have included ELISA tests to determine the 5HT concentration in PLs of patients suffering from migraine headache or syncope. All of our investigations to date have evaluated patients for a deficiency of the PL storage pool (DG SPD) including a decrease of PL DGs and their stored biochemical constituents; we have never conducted a study related to potentially increased numbers of DGs or the concentration of biochemicals contained in these granules. As at least one report exists in the literature suggesting the potential for thrombophilia in patients diagnosed with an autism spectrum disorder and their families, we decided to assess the platelet storage pool in autistic patients and their families as a potential model of platelet dysfunction due to elevated DGs and/or 5HT levels and/or as a potential biomarker for autism. As the major storage pool of 5HT in the circulation is known to exist in platelet PL DGs, it is possible that a PL DG storage pool could be an important mediator of ASD. Our hypothesis is that autistic children may have elevated numbers of DGs and increased levels of PL 5HT. Peripheral blood samples were obtained from children diagnosed with autism as well as their parents and siblings. Platelets were obtained via centrifugation and DG content determined by electron microscopy and an ELISA assay was utilized to determine PL 5HT concentration for all subjects. A questionnaire was also used to evaluate family bleeding history and drug therapy for the autistic children. At present, 4 families have been recruited for the study. Autistic children (n = 5) have an average of 5.42 ± 0.69 DG/PL and a mean 5HT concentration of 447.6.4 ± 85.6 ng/109 PL (PL 5HT normal range = 215-850 ng/109 PL). Their parents have an average of 5.00 ± 0.54 DG/PL and a mean 5HT concentration of 427.6.4 ± 82.66 ng/109 PL and one five year old sibling was found to have 8.17 DG/PL and 2233 ng/109 PL. Control subjects (n=21) have an average of 4.16 ± 0.09 DG/PL and a 5HT concentration of 589.6 ± 56.25 ng/109. There is no statistically significant difference between controls, parents or autistic subjects by ANOVA. Our preliminary data does not support our hypothesis. However, with serotonin being the immediate precursor of melatonin, we do not discount the fact that all of our subjects were receiving drug therapies including melatonin supplementation (n=2) or selective serotonin reuptake inhibitors (n=3) which diminish the PL 5HT concentration. Thus, the therapeutic regimens for these subjects could account for their normal 5HT levels. This project had been initiated just prior to the time of abstract submission; we are currently recruiting study participants and will present additional data at the meeting. Disclosures: No relevant conflicts of interest to declare.