Relationship between whole blood serotonin and repetitive behaviors in autism

Abstract

This study was conducted to examine the relationship between whole blood serotonin level and behavioral symptoms in 78 subjects with autism. No significant associations were found between serotonin level and the primary behavioral outcome measures. However, a significant inverse relationship between serotonin level and self-injury was demonstrated. Keywordsautism; serotonin; repetitive behavior; self-injury; aggression INTRODUCTIONAutism is a severe neurodevelopmental disorder. Its etiology most probably resides primarily in complex genetics and genetic heterogeneity likely accounts for the historic difficulty in reliably identifying susceptibility genes. Autistic symptoms are also well recognized in many other genetic disorders with disparate etiologies, and it is possible that these symptoms represent a phenotype with a common neurochemical substrate (Chugani, 2002). Genetic analysis would greatly benefit from the identification of specific quantitative characteristics, such as biochemical measures. Quantitative measures such as whole blood serotonin may help identify a subgroup of patients with a homogeneous phenotype and provide a complementary strategy for genetic studies beyond relying on qualitative criteria such as those elicited from the widely used Autism Diagnostic Interview-Revised (ADI-R). Biochemical investigation in autism may also potentially identify subgroups that are pathophysiologically related and the Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. (Kuperman et al., 1985) and sibling recurrence (Piven et al., 1991). NIH Public AccessBeginning with a study by Schain and Freedman in 1961, most investigators have found that serotonin levels measured in whole blood are significantly higher in autistic subjects as compared to normal controls, and approximately one-third of autistic individuals are considered to have hyperserotonemia. There is also a significant body of evidence to support the notion that serotonin plays an important role in brain development and affects a range of social behavior, affect regulation, aggression, and anxiety. Recent neuroimaging studies are noteworthy in their ability to demonstrate developmental changes in brain serotonin synthesis capacity and using positron emission tomography (PET), Chugani et al. (1999) found significant differences between autistic and nonautistic children in serotonin synthesis capacity. These results must be interpreted with caution because of the methodology employed, but may suggest that there is a disruption in the mechanisms that regulate serotonin synthesis during development in autism....

The serotonin system in autism spectrum disorder: From biomarker to animal models

“…Several groups have attempted to find clinical correlates of hyperserotonemia in ASD but with mixed results for symptoms such as stereotypic and self-injurious behavior and with some inconsistency across studies (McBride et al, 1998, Mulder et al, 2004, Kolevzon et al, 2010, Sacco et al, 2010). The relationship between hyperserotonemia and other ASD symptoms or frequently co-occurring disorders has been underexplored, including systems that are known to relate to 5-HT function, such as sensory function and gastrointestinal symptoms.…”

The combined role of serotonin and interleukin-6 as biomarker for autism

“…Hyperserotonemia, or elevated blood 5-HT levels are occurred in 25-35% of individuals with ASD (Hanley et al, 1977;Cook et al, 1993;Hranilovic et al, 2007). Some data suggested an association of hyperserotonemia with stereotyped or self-injurious behavior, although results have been inconsistent (Kolevzon et al, 2010;Sacco et al, 2010;Veenstra-VanderWeele et al, 2012). Abnormalities in the brain serotonin system are also reported in ASD, including evidence of altered serotonin synthesis and receptor binding, as well as dystrophic serotonergic axons (Chugani et al, 1997;Makkonen et al, 2008;Nakamura et al, 2010;Azmitia et al, 2011).…”

Dystrophic Serotonin Axons in Postmortem Brains from Young Autism Patients

“…Since Schain and Freedman (1961) first suggested a link between autism and serotonin, more than 500 papers have subsequently been published in support of this association (Kolevzon et al, 2010; West et al, 2009; Carneiro et. al., 2008; Goldberg et.…”