Clinical, cognitive and neuroanatomical associations of serum NMDAR autoantibodies in people at clinical high risk for psychosis The EUGEI High-Risk Study

Autor: Pollak, Thomas, Kempton, Matthew, Iyegbe, Conrad, Vincent, Angela, Irani, Sarosh R, Coutinho, Ester, Menassa, David A, Jacobson, Leslie, De Haan, Lieuwe, Ruhrmann, Stephan, Sachs, Gabriele, Riecher-Rössler, Anita, Krebs, Marie-Odile, Amminger, Paul, Glenthøj, Birte, Barrantes-Vidal, Neus, Van Os, Jim, Rutten, Bart, Bressan, Rodrigo, Van Der Gaag, Mark, Yolken, Robert, Hotopf, Matthew, Valmaggia, Lucia, Stone, James, David, Anthony S, McGuire, Philip
Přispěvatelé: Martinez Rico, Clara, King‘s College London, South London and Maudsley NHS Foundation Trust, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital [Oxford University Hospital], University of Southampton, University of Amsterdam [Amsterdam] (UvA), University of Cologne, Medizinische Universität Wien = Medical University of Vienna, University of Basel (Unibas), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), University of Melbourne, IT University of Copenhagen (ITU), Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), Brain Centre Rudolf Magnus [Utrecht], University Medical Center [Utrecht], Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Universidade Federal de São Paulo, Vrije Universiteit Amsterdam [Amsterdam] (VU), Johns Hopkins University School of Medicine [Baltimore], University College of London [London] (UCL), EUGEI High-Risk Study: Maria Calem, Stefania Tognin, Gemma Modinos, Lieuwe de Haan, Mark van der Gaag, Eva Velthorst, Tamar C Kraan, Daniella S van Dam, Nadine Burger, Barnaby Nelson, Patrick McGorry, Christos Pantelis, Athena Politis, Joanne Goodall, Stefan Borgwardt, Sarah Ittig, Erich Studerus, Renata Smieskova, Ary Gadelha, Elisa Brietzke, Graccielle Asevedo, Elson Asevedo, Andre Zugman, Araceli Rosa, Anna Racioppi, Manel Monsonet, Lídia Hinojosa-Marqués, Thomas R Kwapil, Mathilde Kazes, Claire Daban, Julie Bourgin, Olivier Gay, Célia Mam-Lam-Fook, Dorte Nordholm, Lasse Randers, Kristine Krakauer, Louise Glenthøj, Merete Nordentoft, Dominika Gebhard, Julia Arnhold, Joachim Klosterkötter, Iris Lasser, Bernadette Winklbaur, Philippe A Delespaul, Jim van Os, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), IT University of Copenhagen, VU University Amsterdam, Vrije universiteit = Free university of Amsterdam [Amsterdam] (VU)
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Molecular Psychiatry
Molecular Psychiatry, Nature Publishing Group, 2020, Online ahead of
ISSN: 1359-4184
1476-5578
Popis: International audience; Serum neuronal autoantibodies, such as those to the NMDA receptor (NMDAR), are detectable in a subgroup of patients with psychotic disorders. It is not known if they are present before the onset of psychosis or whether they are associated with particular clinical features or outcomes. In a case-control study, sera from 254 subjects at clinical high risk (CHR) for psychosis and 116 healthy volunteers were tested for antibodies against multiple neuronal antigens implicated in CNS autoimmune disorders, using fixed and live cell-based assays (CBAs). Within the CHR group, the relationship between NMDAR antibodies and symptoms, cognitive function and clinical outcomes over 24 month follow-up was examined. CHR subjects were not more frequently seropositive for neuronal autoantibodies than controls (8.3% vs. 5.2%; OR = 1.50; 95% CI: 0.58-3.90). The NMDAR was the most common target antigen and NMDAR IgGs were more sensitively detected with live versus fixed CBAs (p < 0.001). Preliminary phenotypic analyses revealed that within the CHR sample, the NMDAR antibody seropositive subjects had higher levels of current depression, performed worse on the Rey Auditory Verbal Learning Task (p < 0.05), and had a markedly lower IQ (p < 0.01). NMDAR IgGs were not more frequent in subjects who later became psychotic than those who did not. NMDAR antibody serostatus and titre was associated with poorer levels of functioning at follow-up (p < 0.05) and the presence of a neuronal autoantibody was associated with larger amygdala volumes (p < 0.05). Altogether, these findings demonstrate that NMDAR autoantibodies are detectable in a subgroup of CHR subjects at equal rates to controls. In the CHR group, they are associated with affective psychopathology, impairments in verbal memory, and overall cognitive function: these findings are qualitatively and individually similar to core features of autoimmune encephalitis and/or animal models of NMDAR antibody-mediated CNS disease. Overall the current work supports further evaluation of NMDAR autoantibodies as a possible prognostic biomarker and aetiological factor in a subset of people already meeting CHR criteria.
Databáze: OpenAIRE
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