Neonatal Cytokine Profiles Associated With Autism Spectrum Disorder
Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that can be reliably diagnosed at age 24 months. Immunological phenomena, including skewed cytokine production, have been observed among children with ASD. Little is known about whether immune dysregulation is present before di...
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| Published in | Biological psychiatry (1969) Vol. 81; no. 5; pp. 442 - 451 |
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| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | English |
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United States
Elsevier Inc
01.03.2017
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| Online Access | Get full text |
| ISSN | 0006-3223 1873-2402 1873-2402 |
| DOI | 10.1016/j.biopsych.2015.08.007 |
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| Abstract | Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that can be reliably diagnosed at age 24 months. Immunological phenomena, including skewed cytokine production, have been observed among children with ASD. Little is known about whether immune dysregulation is present before diagnosis of ASD.
We examined neonatal blood spots from 214 children with ASD (141 severe, 73 mild/moderate), 62 children with typical development, and 27 children with developmental delay as control subjects who participated in the Childhood Autism Risks from Genetics and the Environment study, a population-based case-control study. Levels of 17 cytokines and chemokines were compared across groups and in relation to developmental and behavioral domains.
Interleukin (IL)-1β and IL-4 were independently associated with ASD compared with typical development, although these relationships varied by ASD symptom intensity. Elevated IL-4 was associated with increased odds of severe ASD (odds ratio [OR] = 1.40, 95% confidence interval [CI], 1.03, 1.91), whereas IL-1β was associated with increased odds of mild/moderate ASD (OR = 3.02, 95% CI, 1.43, 6.38). Additionally, IL-4 was associated with a higher likelihood of severe ASD versus mild/moderate ASD (OR = 1.35, 95% CI, 1.04, 1.75). In male subjects with ASD, IL-4 was negatively associated with nonverbal cognitive ability (β = −3.63, SE = 1.33, p = .04).
This study is part of a growing effort to identify early biological markers for ASD. We demonstrate that peripheral cytokine profiles at birth are associated with ASD later in childhood and that cytokine profiles vary depending on ASD severity. Cytokines have complex roles in neurodevelopment, and dysregulated levels may be indicative of genetic differences and environmental exposures or their interactions that relate to ASD. |
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| AbstractList | Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that can be reliably diagnosed at age 24 months. Immunological phenomena, including skewed cytokine production, have been observed among children with ASD. Little is known about whether immune dysregulation is present before diagnosis of ASD.
We examined neonatal blood spots from 214 children with ASD (141 severe, 73 mild/moderate), 62 children with typical development, and 27 children with developmental delay as control subjects who participated in the Childhood Autism Risks from Genetics and the Environment study, a population-based case-control study. Levels of 17 cytokines and chemokines were compared across groups and in relation to developmental and behavioral domains.
Interleukin (IL)-1β and IL-4 were independently associated with ASD compared with typical development, although these relationships varied by ASD symptom intensity. Elevated IL-4 was associated with increased odds of severe ASD (odds ratio [OR] = 1.40, 95% confidence interval [CI], 1.03, 1.91), whereas IL-1β was associated with increased odds of mild/moderate ASD (OR = 3.02, 95% CI, 1.43, 6.38). Additionally, IL-4 was associated with a higher likelihood of severe ASD versus mild/moderate ASD (OR = 1.35, 95% CI, 1.04, 1.75). In male subjects with ASD, IL-4 was negatively associated with nonverbal cognitive ability (β = -3.63, SE = 1.33, p = .04).
This study is part of a growing effort to identify early biological markers for ASD. We demonstrate that peripheral cytokine profiles at birth are associated with ASD later in childhood and that cytokine profiles vary depending on ASD severity. Cytokines have complex roles in neurodevelopment, and dysregulated levels may be indicative of genetic differences and environmental exposures or their interactions that relate to ASD. AbstractBackgroundAutism spectrum disorder (ASD) is a complex neurodevelopmental condition that can be reliably diagnosed at age 24 months. Immunological phenomena, including skewed cytokine production, have been observed among children with ASD. Little is known about whether immune dysregulation is present before diagnosis of ASD. MethodsWe examined neonatal blood spots from 214 children with ASD (141 severe, 73 mild/moderate), 62 children with typical development, and 27 children with developmental delay as control subjects who participated in the Childhood Autism Risks from Genetics and the Environment study, a population-based case-control study. Levels of 17 cytokines and chemokines were compared across groups and in relation to developmental and behavioral domains. ResultsInterleukin (IL)-1β and IL-4 were independently associated with ASD compared with typical development, although these relationships varied by ASD symptom intensity. Elevated IL-4 was associated with increased odds of severe ASD (odds ratio [OR] = 1.40, 95% confidence interval [CI], 1.03, 1.91), whereas IL-1β was associated with increased odds of mild/moderate ASD (OR = 3.02, 95% CI, 1.43, 6.38). Additionally, IL-4 was associated with a higher likelihood of severe ASD versus mild/moderate ASD (OR = 1.35, 95% CI, 1.04, 1.75). In male subjects with ASD, IL-4 was negatively associated with nonverbal cognitive ability (β = −3.63, SE = 1.33, p = .04). ConclusionsThis study is part of a growing effort to identify early biological markers for ASD. We demonstrate that peripheral cytokine profiles at birth are associated with ASD later in childhood and that cytokine profiles vary depending on ASD severity. Cytokines have complex roles in neurodevelopment, and dysregulated levels may be indicative of genetic differences and environmental exposures or their interactions that relate to ASD. Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that can be reliably diagnosed at age 24 months. Immunological phenomena, including skewed cytokine production, have been observed among children with ASD. Little is known about whether immune dysregulation is present before diagnosis of ASD.BACKGROUNDAutism spectrum disorder (ASD) is a complex neurodevelopmental condition that can be reliably diagnosed at age 24 months. Immunological phenomena, including skewed cytokine production, have been observed among children with ASD. Little is known about whether immune dysregulation is present before diagnosis of ASD.We examined neonatal blood spots from 214 children with ASD (141 severe, 73 mild/moderate), 62 children with typical development, and 27 children with developmental delay as control subjects who participated in the Childhood Autism Risks from Genetics and the Environment study, a population-based case-control study. Levels of 17 cytokines and chemokines were compared across groups and in relation to developmental and behavioral domains.METHODSWe examined neonatal blood spots from 214 children with ASD (141 severe, 73 mild/moderate), 62 children with typical development, and 27 children with developmental delay as control subjects who participated in the Childhood Autism Risks from Genetics and the Environment study, a population-based case-control study. Levels of 17 cytokines and chemokines were compared across groups and in relation to developmental and behavioral domains.Interleukin (IL)-1β and IL-4 were independently associated with ASD compared with typical development, although these relationships varied by ASD symptom intensity. Elevated IL-4 was associated with increased odds of severe ASD (odds ratio [OR] = 1.40, 95% confidence interval [CI], 1.03, 1.91), whereas IL-1β was associated with increased odds of mild/moderate ASD (OR = 3.02, 95% CI, 1.43, 6.38). Additionally, IL-4 was associated with a higher likelihood of severe ASD versus mild/moderate ASD (OR = 1.35, 95% CI, 1.04, 1.75). In male subjects with ASD, IL-4 was negatively associated with nonverbal cognitive ability (β = -3.63, SE = 1.33, p = .04).RESULTSInterleukin (IL)-1β and IL-4 were independently associated with ASD compared with typical development, although these relationships varied by ASD symptom intensity. Elevated IL-4 was associated with increased odds of severe ASD (odds ratio [OR] = 1.40, 95% confidence interval [CI], 1.03, 1.91), whereas IL-1β was associated with increased odds of mild/moderate ASD (OR = 3.02, 95% CI, 1.43, 6.38). Additionally, IL-4 was associated with a higher likelihood of severe ASD versus mild/moderate ASD (OR = 1.35, 95% CI, 1.04, 1.75). In male subjects with ASD, IL-4 was negatively associated with nonverbal cognitive ability (β = -3.63, SE = 1.33, p = .04).This study is part of a growing effort to identify early biological markers for ASD. We demonstrate that peripheral cytokine profiles at birth are associated with ASD later in childhood and that cytokine profiles vary depending on ASD severity. Cytokines have complex roles in neurodevelopment, and dysregulated levels may be indicative of genetic differences and environmental exposures or their interactions that relate to ASD.CONCLUSIONSThis study is part of a growing effort to identify early biological markers for ASD. We demonstrate that peripheral cytokine profiles at birth are associated with ASD later in childhood and that cytokine profiles vary depending on ASD severity. Cytokines have complex roles in neurodevelopment, and dysregulated levels may be indicative of genetic differences and environmental exposures or their interactions that relate to ASD. Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that can be reliably diagnosed at age 24 months. Immunological phenomena, including skewed cytokine production, have been observed among children with ASD. Little is known about whether immune dysregulation is present before diagnosis of ASD. We examined neonatal blood spots from 214 children with ASD (141 severe, 73 mild/moderate), 62 children with typical development, and 27 children with developmental delay as control subjects who participated in the Childhood Autism Risks from Genetics and the Environment study, a population-based case-control study. Levels of 17 cytokines and chemokines were compared across groups and in relation to developmental and behavioral domains. Interleukin (IL)-1β and IL-4 were independently associated with ASD compared with typical development, although these relationships varied by ASD symptom intensity. Elevated IL-4 was associated with increased odds of severe ASD (odds ratio [OR] = 1.40, 95% confidence interval [CI], 1.03, 1.91), whereas IL-1β was associated with increased odds of mild/moderate ASD (OR = 3.02, 95% CI, 1.43, 6.38). Additionally, IL-4 was associated with a higher likelihood of severe ASD versus mild/moderate ASD (OR = 1.35, 95% CI, 1.04, 1.75). In male subjects with ASD, IL-4 was negatively associated with nonverbal cognitive ability (β = −3.63, SE = 1.33, p = .04). This study is part of a growing effort to identify early biological markers for ASD. We demonstrate that peripheral cytokine profiles at birth are associated with ASD later in childhood and that cytokine profiles vary depending on ASD severity. Cytokines have complex roles in neurodevelopment, and dysregulated levels may be indicative of genetic differences and environmental exposures or their interactions that relate to ASD. |
| Author | Hansen, Robin L. Hertz-Picciotto, Irva Van de Water, Judy Goines, Paula E. Ashwood, Paul Krakowiak, Paula Tancredi, Daniel J. |
| AuthorAffiliation | d Department of Pediatrics, School of Medicine, University of California, Davis e Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis b Division of Rheumatology, Allergy and Clinical Immunology, Department of Internal Medicine, School of Medicine, University of California, Davis f Division of Developmental Behavioral Pediatrics, Department of Pediatrics, School of Medicine, University of California, Davis c MIND (Medical Investigations of Neurodevelopmental Disorders) Institute, University of California, Davis a Divisions of Epidemiology and of Environmental and Occupational Health, Department of Public Health Sciences, School of Medicine, University of California, Davis |
| AuthorAffiliation_xml | – name: d Department of Pediatrics, School of Medicine, University of California, Davis – name: b Division of Rheumatology, Allergy and Clinical Immunology, Department of Internal Medicine, School of Medicine, University of California, Davis – name: e Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis – name: c MIND (Medical Investigations of Neurodevelopmental Disorders) Institute, University of California, Davis – name: a Divisions of Epidemiology and of Environmental and Occupational Health, Department of Public Health Sciences, School of Medicine, University of California, Davis – name: f Division of Developmental Behavioral Pediatrics, Department of Pediatrics, School of Medicine, University of California, Davis |
| Author_xml | – sequence: 1 givenname: Paula orcidid: 0000-0001-9329-0892 surname: Krakowiak fullname: Krakowiak, Paula organization: Divisions of Epidemiology and of Environmental and Occupational Health, University of California, Davis, Davis, California – sequence: 2 givenname: Paula E. surname: Goines fullname: Goines, Paula E. organization: Department of Public Health Sciences, Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, Davis, California – sequence: 3 givenname: Daniel J. surname: Tancredi fullname: Tancredi, Daniel J. organization: Department of Internal Medicine, Department of Pediatrics, University of California, Davis, Davis, California – sequence: 4 givenname: Paul surname: Ashwood fullname: Ashwood, Paul organization: Department of Medical Microbiology and Immunology, University of California, Davis, Davis, California – sequence: 5 givenname: Robin L. surname: Hansen fullname: Hansen, Robin L. organization: School of Medicine, and MIND (Medical Investigations of Neurodevelopmental Disorders) Institute, University of California, Davis, Davis, California – sequence: 6 givenname: Irva surname: Hertz-Picciotto fullname: Hertz-Picciotto, Irva organization: Divisions of Epidemiology and of Environmental and Occupational Health, University of California, Davis, Davis, California – sequence: 7 givenname: Judy surname: Van de Water fullname: Van de Water, Judy email: javandewater@ucdavis.edu organization: Department of Public Health Sciences, Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, Davis, California |
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| Copyright | 2016 Society of Biological Psychiatry Society of Biological Psychiatry Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved. |
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| Keywords | Neurodevelopment Blood spot Neonatal cytokines Autism spectrum disorder Chemokines Developmental delays |
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| Snippet | Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that can be reliably diagnosed at age 24 months. Immunological phenomena, including... AbstractBackgroundAutism spectrum disorder (ASD) is a complex neurodevelopmental condition that can be reliably diagnosed at age 24 months. Immunological... |
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| SubjectTerms | Autism spectrum disorder Autism Spectrum Disorder - blood Autism Spectrum Disorder - diagnosis Autism Spectrum Disorder - immunology Biomarkers - blood Blood spot Case-Control Studies Chemokines Child, Preschool Cytokines - blood Cytokines - immunology Developmental delays Female Humans Interleukin-1beta - blood Interleukin-1beta - immunology Interleukin-4 - blood Interleukin-4 - immunology Male Neonatal cytokines Neurodevelopment Psychiatric/Mental Health Severity of Illness Index |
| Title | Neonatal Cytokine Profiles Associated With Autism Spectrum Disorder |
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