Serum Serotonin Levels As a Biomarker of Autism Severity

Background: Despite remarkable inter-individual differences at the clinical level, individuals with autism spectrum disorders (ASD) essentially share two major clinical characteristics: 1) deficits in social interaction and communication and; 2) behavioral abnormalities, such as stereotypic behaviors, insistence on sameness and/or restricted interests. This clinical heterogeneity and its molecular complexities have driven increasing interest into biomarkers. Biological markers can be defined as a biological variable associated with the disease of interest and is measured directly in a patient´s biomaterial using sensitive and reliable quantitative procedures. Those measurable parameters could facilitate earlier and more reliable diagnosis, as well as the identification of subgroups of patients sharing common pathophysiological aspects.

Objectives: This study aimed to evaluate the serum serotonin level and its relationship with the severity of the symptoms in the child with autism.

Methods: A comparative cross-sectional study was performed with 140 children diagnosed with ASD (70 classified into mild/moderate and 70 classified into severe autism), and 65 healthy controls. Their ages ranged from 2 to 11 years old. The diagnosis of ASD was confirmed by the Diagnostic and Statistical Manual of Mental Disorders, 5^th Edition (DSM-V) and the severity was assessed by the Childhood Autism Rating Scale (CARS). Serum serotonin levels were determined through high performance liquid chromatography (HPLC).

Results: Serum serotonin levels were significantly increased in autistic children when compared to gender matched controls. Serotonin levels were in 170,62+/-67,17 ng/dL in mild/moderate and 304,98+/-90,05 ng/dL in severe autistic patients. While serotonin levels were 136,25+/-46,30 ng/dL in controls. Applying univariate regression analysis, serum serotonin levels above 200 ng/dL represented a 13 fold increased risk of revealing a case of severe autism.

Conclusions: Previous studies have hypothesized that a disruption in the synaptogenesis plays an important role in the pathophysiology of autism. In this regard, many evidences suggest that the different systems of neurotransmission may be involved in autism. Serotonin (5-hidroxytryptamine; 5-HT) is a neurotransmitter which is involved in modulating cortical plasticity with a significant role in early cortex development as a regulator of neuronal proliferation, migration and differentiation. Association studies, aiming to demonstrate that serum serotonin levels may represent a good biomarker of the susceptibility of autism, however, had controversial results. The results of this study were in accordance with previously obtained data that demonstrates a significant elevation in the levels of serum serotonin in autistic children when compared to healthy control subjects. An even more interesting result, was a significant positive correlation between elevated serum serotonin levels and autism severity.