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Research paper
CASPR2 autoantibodies are raised during pregnancy in mothers of children with mental retardation and disorders of psychological development but not autism
  1. Ester Coutinho1,
  2. Leslie Jacobson1,
  3. Marianne Giørtz Pedersen2,3,
  4. Michael Eriksen Benros2,3,4,
  5. Bent Nørgaard-Pedersen5,
  6. Preben Bo Mortensen2,3,6,
  7. Paul J Harrison7,8,
  8. Angela Vincent1
  1. 1 Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
  2. 2 Department of Economics and Business Economics, National Centre for Register-based Research, Aarhus University, Aarhus, Denmark
  3. 3 iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark
  4. 4 Mental Health Centre Copenhagen, University of Copenhagen, Faculty of Health Sciences, Copenhagen, Denmark
  5. 5 Department of Congenital Disorders, Danish Centre for Neonatal Screening, Statens Serum Institut, Copenhagen, Denmark
  6. 6 Centre for Integrated Register-Based Research (CIRRAU), Aarhus University, Aarhus, Denmark
  7. 7 Department of Psychiatry, University of Oxford, Oxford, UK
  8. 8 Oxford Health NHS Foundation Trust, Oxford, Oxfordshire, UK
  1. Correspondence to Professor Angela Vincent, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford OX3 9DU, UK; angela.vincent{at}ndcn.ox.ac.uk

Abstract

Background, Methods and Objectives Maternal autoantibodies to neuronal proteins may be one cause of neurodevelopmental disorders. This exploratory study used the Danish archived midgestational sera and their nationwide registers to search for antibodies to the N-methyl-D-aspartate receptor (NMDAR) and contactin-associated protein-like 2 (CASPR2) in maternal sera, and to relate them to subsequent psychiatric diagnoses in the woman or her child.

Results In a sample of 192 women, there was no association between antibody status and subsequent psychosis in the mothers. However, NMDAR antibodies (n=4) or CASPR2 antibodies (n=1) were identified in 5/11 (45.5%) women whose children were given a diagnosis of mild or unspecified mental retardation or disorders of psychological and motor development (collectively abbreviated as mental retardation and/or disorders of psychological development (MR/DPD)) compared with 9/176 (5.1%) of the remaining mother (p<0.001). These findings were followed up in a specifically selected cohort, in which CASPR2 antibodies were detected in 7/171 (4.1%) mothers of MR/DPD progeny, compared with only 1/171 (0.6%) control mother (p=0.067). The combined sample showed a significantly higher frequency of CASPR2 antibodies in mothers of MD/DPD children (p=0.01). These autoantibodies were not increased in mothers of children with autistic spectrum disorder.

Conclusions These findings complement the known roles of CASPR2 in brain development, and warrant further epidemiological and experimental studies to clarify the role of CASPR2 and possibly other antibodies in neurodevelopmental disorders.

  • CASPR2
  • antibodies
  • intellectual disability
  • autism

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

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Footnotes

  • Contributors EC and AV conceptualised the study. EC and AV were responsible for methodology. EC, LJ, MGP and MEB conducted the investigation. AV obtained resources. PH, PBM, BN-P and AV supervised the study. EC and AV wrote the manuscript. All authors revised the manuscript.

  • Funding EC is funded by Programme for Advanced Medical Education, Fundação Calouste Gulbenkian. This work was also supported by the Stanley Medical Research Institute.

  • Competing interests AV and the University of Oxford hold a patent for LG11 and CASPR2 antibodies, licensed to Euroimmun AG, and receive a proportion of royalties for autoimmune encephalitis diagnostics.

  • Patient consent Historical cohort under Danish research ethics.

  • Ethics approval Danish Data Protection Agency and the Research Ethics Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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