Gastrointestinal Symptoms, Whole Blood Serotonin Levels, and Behavioral Symptoms in Children and Adolescents with Autism Spectrum Disorder

Background: Autism spectrum disorder (ASD) is characterized by social communication deficits and repetitive behavior, but several co-occurring medical disorders are also increased in ASD. Constipation appears to be particularly common, occurring in 32% of children in the Autism Speaks Autism Treatment Network (Peters et al., 2014). In parallel, elevated whole blood serotonin, or hyperserotonemia, is a well-replicated, heritable biomarker occurring in a subgroup of approximately 28% of children with ASD (Gabriele et al., 2014). In the periphery, serotonin (5-hydroxytryptamine, 5-HT) is synthesized in gut enterochromaffin cells that release it into the blood, where >99% of whole blood 5-HT is found stored in platelets. Within the gastrointestinal (GI) system, 5-HT regulates multiple processes, including motility and inflammation (Gershon, 2014). To our knowledge, no previous study has examined the relationship between gastrointestinal symptoms and whole blood 5-HT levels in ASD. Previous studies have separately examined behavioral correlates in these ASD subgroups, with some but not all studies finding elevated rates of self-injury, repetitive behavior, sensory processing difficulties, and heightened stress reactivity associated with either GI symptoms or elevated blood 5-HT levels.

Objectives: Our primary aim was to investigate the relationship between gut symptoms, particularly functional constipation, and whole blood 5-HT levels in children and adolescents with ASD. We also aimed to assess the relationship between functional constipation, whole blood 5-HT levels, and previously reported behavioral correlates.

Methods: This multicenter study involved a sample of 81 children with ASD, ages 6-18, with and without GI symptoms. The Questionnaire on Pediatric Gastrointestinal Symptoms—Rome III Version (QPGS-RIII) was used to assess GI disorders. Whole blood serotonin was measured by high-performance liquid chromatography. Sensory symptoms, repetitive behavior, and anxiety were assessed using caregiver reported measures. Stress reactivity was assessed by heart rate variability during two stress-inducing tasks.

Results: Functional constipation (FC) was the most common Rome III diagnosis, occurring in 42% (34/81) of the sample. Participants with functional constipation did not differ from those with no GI diagnosis on age, sex, race, ethnicity, or IQ. Comparing to previous norms (McBride et al., 1998), 23% (19/81) of the participants had 5-HT levels two standard deviations above the mean for their age, sex, and race. Whole blood 5-HT levels, corrected for age and sex, were not significantly different in the functional constipation group in comparison to those with no GI diagnosis (p = 0.18). Behavioral measures and stress reactivity were not different in the hyperserotonemic or in the functional constipation subgroups in comparison to the rest of the sample.

Conclusions: No association between functional constipation and whole blood serotonin was observed in this population of children with ASD. These are preliminary analyses, with further analysis ongoing to include measurement of inflammatory markers.