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Maternal autoimmunity and inflammation are associated with childhood tics and obsessive-compulsive disorder: Transcriptomic data show common enriched innate immune pathways.
Jones, Hannah F; Han, Velda X; Patel, Shrujna; Gloss, Brian S; Soler, Nicolette; Ho, Alvin; Sharma, Suvasini; Kothur, Kavitha; Nosadini, Margherita; Wienholt, Louise; Hardwick, Chris; Barnes, Elizabeth H; Lim, Jacqueline R; Alshammery, Sarah; Nielsen, Timothy C; Wong, Melanie; Hofer, Markus J; Nassar, Natasha; Gold, Wendy; Brilot, Fabienne; Mohammad, Shekeeb S; Dale, Russell C.
Afiliación
  • Jones HF; Kids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; Department of Neuroservices, Starship Children's Hospital, Auckland, New Zealand; The Children's Hospital at Westmead Clinical School, Faculty of M
  • Han VX; Kids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore.
  • Patel S; Kids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; The Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
  • Gloss BS; Westmead Research Hub, Westmead Institute for Medical Research, Westmead, Sydney, New South Wales, Australia.
  • Soler N; Kids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; The Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; Depa
  • Ho A; Kids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, Hong Kong.
  • Sharma S; Kids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; Neurology Division, Department of Paediatrics, Lady Hardinge Medical College and Associated Kalawati Saran Children's Hospital, New Delhi, India.
  • Kothur K; Kids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; The Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
  • Nosadini M; Kids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; Paediatric Neurology Unit, Department of Paediatrics, University of Padua, Italy.
  • Wienholt L; The Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; Department of Clinical Immunology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.
  • Hardwick C; Department of Psychological Medicine, The Children's Hospital at Westmead, Sydney, New South Wales, Australia.
  • Barnes EH; NHMRC Clinical Trials Centre, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
  • Lim JR; The Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
  • Alshammery S; Kids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; The Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
  • Nielsen TC; Child Population and Translational Health Research, The Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
  • Wong M; Department of Immunology, The Children's Hospital at Westmead, Sydney, New South Wales, Australia.
  • Hofer MJ; School of Life and Environmental Sciences and Charles Perkins Centre, Faculty of Science, University of Sydney, Sydney, New South Wales, Australia.
  • Nassar N; Child Population and Translational Health Research, The Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
  • Gold W; Kids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; The Children's Medical Resear
  • Brilot F; Kids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; The Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; The
  • Mohammad SS; Kids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; The Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
  • Dale RC; Kids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; The Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; The
Brain Behav Immun ; 94: 308-317, 2021 05.
Article en En | MEDLINE | ID: mdl-33422639
ABSTRACT
Although genetic variation is a major risk factor of neurodevelopmental disorders, environmental factors during pregnancy and early life are also important in disease expression. Animal models demonstrate that maternal inflammation causes fetal neuroinflammation and neurodevelopmental deficits, and brain transcriptomics of neurodevelopmental disorders in humans show upregulated differentially expressed genes are enriched in immune pathways. We prospectively recruited 200 sequentially referred children with tic disorders/obsessive-compulsive disorder (OCD), 100 autoimmune neurological controls, and 100 age-matched healthy controls. A structured interview captured the maternal and family history of autoimmune disease and other pro-inflammatory states. Maternal blood and published Tourette brain transcriptomes were analysed for overlapping enriched pathways. Mothers of children with tics/OCD had a higher rate of autoimmune disease compared with mothers of children with autoimmune neurological conditions (p = 0.054), and mothers of healthy controls (p = 0.0004). Autoimmunity was similarly elevated in first- and second-degree maternal relatives of children with tics/OCD (p < 0.0001 and p = 0.014 respectively). Other pro-inflammatory states were also more common in mothers of children with tics/OCD than controls (p < 0.0001). Upregulated differentially expressed genes in maternal autoimmune disease and Tourette brain transcriptomes were commonly enriched in innate immune processes. Pro-inflammatory states, including autoimmune disease, are more common in the mothers and families of children with tics/OCD. Exploratory transcriptome analysis indicates innate immune signalling may link maternal inflammation and childhood tics/OCD. Targeting inflammation may represent preventative strategies in pregnancy and treatment opportunities for children with neurodevelopmental disorders.
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Trastornos de Tic / Tics / Trastorno Obsesivo Compulsivo Tipo de estudio: Prognostic_studies / Qualitative_research / Risk_factors_studies Límite: Child / Female / Humans / Newborn / Pregnancy Idioma: En Revista: Brain Behav Immun Asunto de la revista: ALERGIA E IMUNOLOGIA / CEREBRO / PSICOFISIOLOGIA Año: 2021 Tipo del documento: Article

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Trastornos de Tic / Tics / Trastorno Obsesivo Compulsivo Tipo de estudio: Prognostic_studies / Qualitative_research / Risk_factors_studies Límite: Child / Female / Humans / Newborn / Pregnancy Idioma: En Revista: Brain Behav Immun Asunto de la revista: ALERGIA E IMUNOLOGIA / CEREBRO / PSICOFISIOLOGIA Año: 2021 Tipo del documento: Article