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Maternal mid-gestational and child cord blood immune signatures are strongly associated with offspring risk of ASD.
Che, Xiaoyu; Hornig, Mady; Bresnahan, Michaeline; Stoltenberg, Camilla; Magnus, Per; Surén, Pål; Mjaaland, Siri; Reichborn-Kjennerud, Ted; Susser, Ezra; Lipkin, W Ian.
Afiliación
  • Che X; Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY, USA.
  • Hornig M; Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY, USA.
  • Bresnahan M; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.
  • Stoltenberg C; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.
  • Magnus P; New York State Psychiatric Institute, New York, NY, USA.
  • Surén P; Norwegian Institute of Public Health, Oslo, Norway.
  • Mjaaland S; Department of Global Public Health, University of Bergen, Bergen, Norway.
  • Reichborn-Kjennerud T; Norwegian Institute of Public Health, Oslo, Norway.
  • Susser E; Norwegian Institute of Public Health, Oslo, Norway.
  • Lipkin WI; Norwegian Institute of Public Health, Oslo, Norway.
Mol Psychiatry ; 27(3): 1527-1541, 2022 03.
Article en En | MEDLINE | ID: mdl-34987169
Epidemiological studies and work in animal models indicate that immune activation may be a risk factor for autism spectrum disorders (ASDs). We measured levels of 60 cytokines and growth factors in 869 maternal mid-gestational (MMG) and 807 child cord blood (CB) plasma samples from 457 ASD (385 boys, 72 girls) and 497 control children (418 boys, 79 girls) from the Norwegian Autism Birth Cohort. We analyzed associations first using sex-stratified unadjusted and adjusted logistic regression models, and then employed machine learning strategies (LASSO + interactions, Random Forests, XGBoost classifiers) with cross-validation and randomly sampled test set evaluation to assess the utility of immune signatures as ASD biomarkers. We found prominent case-control differences in both boys and girls with alterations in a wide range of analytes in MMG and CB plasma including but not limited to IL1RA, TNFα, Serpin E1, VCAM1, VEGFD, EGF, CSF1, and CSF2. MMG findings were most striking, with particularly strong effect sizes in girls. Models did not change appreciably upon adjustment for maternal conditions, medication use, or emotional distress ratings. Findings were corroborated using machine learning approaches, with area under the receiver operating characteristic curve values in the test sets ranging from 0.771 to 0.965. Our results are consistent with gestational immunopathology in ASD, may provide insights into sex-specific differences, and have the potential to lead to biomarkers for early diagnosis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trastorno Autístico / Trastorno del Espectro Autista Tipo de estudio: Etiology_studies / Observational_studies / Prognostic_studies / Screening_studies Límite: Female / Humans / Male Idioma: En Revista: Mol Psychiatry Asunto de la revista: BIOLOGIA MOLECULAR / PSIQUIATRIA Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trastorno Autístico / Trastorno del Espectro Autista Tipo de estudio: Etiology_studies / Observational_studies / Prognostic_studies / Screening_studies Límite: Female / Humans / Male Idioma: En Revista: Mol Psychiatry Asunto de la revista: BIOLOGIA MOLECULAR / PSIQUIATRIA Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido