Thursday, May 20, 2010
Franklin Hall B Level 4 (Philadelphia Marriott Downtown)
1:00 PM
Background: Autism is known to be associated with hyperserotoninemia and, more recently, with decreased blood melatonin level. Melatonin is a neurohormone synthesized from serotonin and involved in circadian rhythms and sleep regulations. Thus, serotonin and melatonin are two ends of a biochemical pathway, and little is known concerning all the steps of this pathway in patients with Autism Spectrum Disorders. Moreover, the clinical relevance of these biochemical endophenotypes remains to be determined.
Objectives: Here we explore the serotonin-melatonin pathway in a large cohort of patients with ASD, in order to (i) better characterize the biochemical abnormalities of this pathway in ASD, (ii) determine the clinical correlates of these biochemical abnormalities, and (iii) assess the relevance of these biochemical parameters as biomarkers for ASD diagnosis.
Methods: The five parameters related to the serotonin-melatonin pathway, i.e. serotonin, arylalkylamine N-acetyltransferase (AA-NAT) enzyme activity, N-acetylserotonin, acetylserotonin methyltransferase (ASMT) enzyme activity, and melatonin, were measured in the blood of 203 patients with ASD, their unaffected relatives (291 parents and 92 sibs), and age- and sex-matched controls. Biochemical data were correlated with clinical data obtained from ADI-R for 117 patients.
Results: Patients with ASD display elevated blood serotonin and N-acetylserotonin levels (p<0,001) compared to controls and unaffected relatives, and decreased ASMT activity and melatonin levels (p<0,001) compared to controls. When confronted to clinical data, melatonin deficiency appears significantly associated with stereotyped behavior (ADI-R axis D, p=0,003). Finally, comparisons between ASD patients, controls and unaffected sibs on the one hand, and between autism and Asperger syndrome on the other hand, reveal that hyperserotoninemia is a relevant biomarker of autism, with good specificity and sensitivity.
Conclusions: This study confirms the previously reported major abnormalities of the serotonin-melatonin pathway in ASD. The typical biochemical profile of ASD patients suggests a deficit of the ASMT enzyme, consistent with our previous work. Serotonin and melatonin are both clinically relevant parameters, serotonin as a specific biomarker of autism, and melatonin for behavioral correlates. These results highlight the clinical interest of the serotonin –melatonin pathway in ASD, and its potential role as a susceptibility factor to autism.
Objectives: Here we explore the serotonin-melatonin pathway in a large cohort of patients with ASD, in order to (i) better characterize the biochemical abnormalities of this pathway in ASD, (ii) determine the clinical correlates of these biochemical abnormalities, and (iii) assess the relevance of these biochemical parameters as biomarkers for ASD diagnosis.
Methods: The five parameters related to the serotonin-melatonin pathway, i.e. serotonin, arylalkylamine N-acetyltransferase (AA-NAT) enzyme activity, N-acetylserotonin, acetylserotonin methyltransferase (ASMT) enzyme activity, and melatonin, were measured in the blood of 203 patients with ASD, their unaffected relatives (291 parents and 92 sibs), and age- and sex-matched controls. Biochemical data were correlated with clinical data obtained from ADI-R for 117 patients.
Results: Patients with ASD display elevated blood serotonin and N-acetylserotonin levels (p<0,001) compared to controls and unaffected relatives, and decreased ASMT activity and melatonin levels (p<0,001) compared to controls. When confronted to clinical data, melatonin deficiency appears significantly associated with stereotyped behavior (ADI-R axis D, p=0,003). Finally, comparisons between ASD patients, controls and unaffected sibs on the one hand, and between autism and Asperger syndrome on the other hand, reveal that hyperserotoninemia is a relevant biomarker of autism, with good specificity and sensitivity.
Conclusions: This study confirms the previously reported major abnormalities of the serotonin-melatonin pathway in ASD. The typical biochemical profile of ASD patients suggests a deficit of the ASMT enzyme, consistent with our previous work. Serotonin and melatonin are both clinically relevant parameters, serotonin as a specific biomarker of autism, and melatonin for behavioral correlates. These results highlight the clinical interest of the serotonin –melatonin pathway in ASD, and its potential role as a susceptibility factor to autism.