Autism with intellectual disability is associated with increased levels of maternal cytokines and chemokines during gestation

K. L. Jones, L. A. Croen, C. K. Yoshida, L. Heuer, Robin L Hansen, O. Zerbo, G. N. DeLorenze, M. Kharrazi, R. Yolken, Paul Ashwood, Judith A Van de Water

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Immune abnormalities have been described in some individuals with autism spectrum disorders (ASDs) as well as their family members. However, few studies have directly investigated the role of prenatal cytokine and chemokine profiles on neurodevelopmental outcomes in humans. In the current study, we characterized mid-gestational serum profiles of 22 cytokines and chemokines in mothers of children with ASD (N=415), developmental delay (DD) without ASD (N=188), and general population (GP) controls (N=428) using a bead-based multiplex technology. The ASD group was further divided into those with intellectual disabilities (developmental/cognitive and adaptive composite score<70) (ASD+ID, N=184) and those without (composite score⩾70) (ASD-noID, N=201). Levels of cytokines and chemokines were compared between groups using multivariate logistic regression analyses, adjusting for maternal age, ethnicity, birth country and weight, as well as infant gender, birth year and birth month. Mothers of children with ASD+ID had significantly elevated mid-gestational levels of numerous cytokines and chemokines, such as granulocyte macrophage colony-stimulating factor, interferon-γ, interleukin-1α (IL-1α) and IL-6, compared with mothers of children with either ASD-noID, those with DD, or GP controls. Conversely, mothers of children with either ASD-noID or with DD had significantly lower levels of the chemokines IL-8 and monocyte chemotactic protein-1 compared with mothers of GP controls. This observed immunologic distinction between mothers of children with ASD+ID from mothers of children with ASD-noID or DD suggests that the intellectual disability associated with ASD might be etiologically distinct from DD without ASD. These findings contribute to the ongoing efforts toward identification of early biological markers specific to subphenotypes of ASD.Molecular Psychiatry advance online publication, 24 May 2016; doi:10.1038/mp.2016.77.

Original languageEnglish (US)
JournalMolecular Psychiatry
DOIs
StateAccepted/In press - May 24 2016

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Autistic Disorder
Chemokines
Intellectual Disability
Mothers
Cytokines
Pregnancy
Population Control
Autism Spectrum Disorder
Parturition
Chemokine CCL2
Maternal Age
Granulocyte-Macrophage Colony-Stimulating Factor
Interleukin-8
Interleukin-1
Birth Weight
Interferons
Psychiatry
Publications
Interleukin-6
Biomarkers

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Autism with intellectual disability is associated with increased levels of maternal cytokines and chemokines during gestation. / Jones, K. L.; Croen, L. A.; Yoshida, C. K.; Heuer, L.; Hansen, Robin L; Zerbo, O.; DeLorenze, G. N.; Kharrazi, M.; Yolken, R.; Ashwood, Paul; Van de Water, Judith A.

In: Molecular Psychiatry, 24.05.2016.

Research output: Contribution to journalArticle

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abstract = "Immune abnormalities have been described in some individuals with autism spectrum disorders (ASDs) as well as their family members. However, few studies have directly investigated the role of prenatal cytokine and chemokine profiles on neurodevelopmental outcomes in humans. In the current study, we characterized mid-gestational serum profiles of 22 cytokines and chemokines in mothers of children with ASD (N=415), developmental delay (DD) without ASD (N=188), and general population (GP) controls (N=428) using a bead-based multiplex technology. The ASD group was further divided into those with intellectual disabilities (developmental/cognitive and adaptive composite score<70) (ASD+ID, N=184) and those without (composite score⩾70) (ASD-noID, N=201). Levels of cytokines and chemokines were compared between groups using multivariate logistic regression analyses, adjusting for maternal age, ethnicity, birth country and weight, as well as infant gender, birth year and birth month. Mothers of children with ASD+ID had significantly elevated mid-gestational levels of numerous cytokines and chemokines, such as granulocyte macrophage colony-stimulating factor, interferon-γ, interleukin-1α (IL-1α) and IL-6, compared with mothers of children with either ASD-noID, those with DD, or GP controls. Conversely, mothers of children with either ASD-noID or with DD had significantly lower levels of the chemokines IL-8 and monocyte chemotactic protein-1 compared with mothers of GP controls. This observed immunologic distinction between mothers of children with ASD+ID from mothers of children with ASD-noID or DD suggests that the intellectual disability associated with ASD might be etiologically distinct from DD without ASD. These findings contribute to the ongoing efforts toward identification of early biological markers specific to subphenotypes of ASD.Molecular Psychiatry advance online publication, 24 May 2016; doi:10.1038/mp.2016.77.",
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