title: Associations between cytokines, endocrine stress response, and gastrointestinal symptoms in autism spectrum disorder.
abstract: Many children and adolescents with autism spectrum disorder (ASD) have significant gastrointestinal (GI) symptoms, but the etiology is currently unknown. Some individuals with ASD show altered reactivity to stress and altered immune markers relative to typically-developing individuals, particularly stress-responsive cytokines including tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6). Acute and chronic stress is associated with the onset and exacerbation of GI symptoms in those without ASD. The present study examined whether GI symptoms in ASD were associated with increases in cortisol, a stress-associated endocrine marker, and TNF-α and IL-6 in response to stress. As hypothesized, a greater amount of lower GI tract symptoms were significantly associated with post-stress cortisol concentration. The relationship between cortisol response to stress and GI functioning was greater for children who had a history of regressive autism. Exploratory analyses revealed significant correlations between cortisol response, intelligence, and inappropriate speech. In contrast, symptoms of the lower GI tract were not associated with levels of TNF-α or IL-6. Significant correlations were found, however, between TNF-α and IL-6 and irritability, socialization, and intelligence. These findings suggest that individuals with ASD and symptoms of the lower GI tract may have an increased response to stress, but this effect is not associated with concomitant changes in TNF-α and IL-6. The relationship between cortisol stress response and lower GI tract symptoms in children with regressive autism, as well as the relationships between cortisol, IL-6, and intelligence in ASD, warrant further investigation.
authors.affiliation: Interdisciplinary Neuroscience Program, University of Missouri, United States; The Thompson Center for Autism and Neurodevelopmental Disorders, University of Missouri, United States.
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Ferguson
authors.affiliation: Department of Child and Adolescent Psychiatry, Vanderbilt University Medical Center, United States.
authors.forename: Sarah
authors.initials: S
authors.lastname: Marler
authors.affiliation: Massachusetts General Hospital Biostatistics Center, United States.
authors.forename: Lily L
authors.initials: LL
authors.lastname: Altstein
authors.affiliation: Departments of Pediatrics, Psychology, and Psychiatry, Vanderbilt University, United States.
authors.forename: Evon Batey
authors.initials: EB
authors.lastname: Lee
authors.affiliation: The Thompson Center for Autism and Neurodevelopmental Disorders, University of Missouri, United States; Department of Health Psychology, University of Missouri, United States.
authors.forename: Micah O
authors.initials: MO
authors.lastname: Mazurek
authors.affiliation: University of Missouri School of Medicine, United States.
authors.forename: Aaron
authors.initials: A
authors.lastname: McLaughlin
authors.affiliation: Massachusetts General Hospital Biostatistics Center, United States; Harvard Medical School, United States.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Macklin
authors.affiliation: Massachusetts General Hospital Biostatistics Center, United States.
authors.forename: Erin
authors.initials: E
authors.lastname: McDonnell
authors.affiliation: Department of Veterinary Pathobiology, University of Missouri, United States.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Davis
authors.affiliation: Department of Nutrition and Exercise Physiology, University of Missouri, United States.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Belenchia
authors.affiliation: Department of Veterinary Pathobiology, University of Missouri, United States.
authors.forename: Catherine H
authors.initials: CH
authors.lastname: Gillespie
authors.affiliation: Department of Nutrition and Exercise Physiology, University of Missouri, United States.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Peterson
authors.affiliation: Boston University School of Medicine, United States.
authors.forename: Margaret L
authors.initials: ML
authors.lastname: Bauman
authors.affiliation: Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Columbia University, United States.
authors.forename: Kara Gross
authors.initials: KG
authors.lastname: Margolis
authors.affiliation: Department of Psychiatry and Sackler Institute for Developmental Psychobiology, Columbia University, United States; New York State Psychiatric Institute, New York Presbyterian Hospital Center for Autism and the Developing Brain, United States.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Veenstra-VanderWeele
authors.affiliation: Interdisciplinary Neuroscience Program, University of Missouri, United States; The Thompson Center for Autism and Neurodevelopmental Disorders, University of Missouri, United States; William and Nancy Thompson Chair in Radiology, Departments of Radiology, Neurology, and Psychological Sciences, University of Missouri, United States. Electronic address: beversdorfd@health.mssouri.edu.
authors.forename: David Q
authors.initials: DQ
authors.lastname: Beversdorf
mesh_terms: D000293:Adolescent; D000067877:Autism Spectrum Disorder / Q000150:complications* / Q000276:immunology*; D002648:Child; D016207:Cytokines / Q000378:metabolism; D004703:Endocrine System / Q000276:immunology; D005260:Female; D005767:Gastrointestinal Diseases / Q000150:complications* / Q000276:immunology*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D013315:Stress, Psychological / Q000150:complications* / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; C508600:IL6 protein, human; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D006854:Hydrocortisone
keywords: Autism spectrum disorder; Cortisol; Cytokines; Gastrointestinal disorders; Stress