PMID- 33077853 OWN - NLM STAT- MEDLINE DCOM- 20211011 LR - 20220722 IS - 1476-5578 (Electronic) IS - 1359-4184 (Print) IS - 1359-4184 (Linking) VI - 26 IP - 6 DP - 2021 Jun TI - Clinical, cognitive and neuroanatomical associations of serum NMDAR autoantibodies in people at clinical high risk for psychosis. PG - 2590-2604 LID - 10.1038/s41380-020-00899-w [doi] AB - 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. CI - (c) 2020. The Author(s). FAU - Pollak, Thomas A AU - Pollak TA AUID- ORCID: 0000-0002-6171-0810 AD - Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's Health Partners, King's College London, London, UK. thomas.pollak@kcl.ac.uk. AD - Precision Psychiatry Cluster, National Institute for Health Research Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London, London, UK. thomas.pollak@kcl.ac.uk. AD - South London and Maudsley NHS Foundation Trust, London, UK. thomas.pollak@kcl.ac.uk. FAU - Kempton, Matthew J AU - Kempton MJ AD - Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's Health Partners, King's College London, London, UK. AD - Precision Psychiatry Cluster, National Institute for Health Research Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London, London, UK. FAU - Iyegbe, Conrad AU - Iyegbe C AD - Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's Health Partners, King's College London, London, UK. FAU - Vincent, Angela AU - Vincent A AUID- ORCID: 0000-0003-2395-8695 AD - Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, UK. FAU - Irani, Sarosh R AU - Irani SR AD - Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, UK. FAU - Coutinho, Ester AU - Coutinho E AD - Division of Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's Health Partners, King's College London, London, UK. FAU - Menassa, David A AU - Menassa DA AD - Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, UK. AD - Biological Sciences, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, UK. FAU - Jacobson, Leslie AU - Jacobson L AD - Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, UK. FAU - de Haan, Lieuwe AU - de Haan L AD - Amsterdam UMC, University of Amsterdam, Psychiatry, Department Early Psychosis, Meibergdreef 9, Amsterdam, The Netherlands. FAU - Ruhrmann, Stephan AU - Ruhrmann S AD - Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital, University of Cologne, Cologne, Germany. FAU - Sachs, Gabriele AU - Sachs G AD - Medical University of Vienna, Department of Psychiatry and Psychotherapy, Vienna, Austria. FAU - Riecher-Rossler, Anita AU - Riecher-Rossler A AD - Medical Faculty, University of Basel, Basel, Switzerland. FAU - Krebs, Marie-Odile AU - Krebs MO AD - University of Paris, GHU-Paris, Sainte-Anne, C'JAAD, Hospitalo-Universitaire department SHU, Inserm U1266, Institut de Psychiatrie (CNRS 3557), Paris, France. FAU - Amminger, Paul AU - Amminger P AD - Centre for Youth Mental Health, University of Melbourne, 35 Poplar Road (Locked Bag 10), Parkville, VIC, 4853052, Australia. AD - Orygen, The National Centre of Excellence in Youth Mental Health, The University of Melbourne, Parkville, VIC, Australia. FAU - Glenthoj, Birte AU - Glenthoj B AD - Centre for Neuropsychiatric Schizophrenia Research (CNSR) & Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark. FAU - Barrantes-Vidal, Neus AU - Barrantes-Vidal N AD - Departament de Psicologia Clinica I de la Salut (Universitat Autonoma de Barcelona), Fundacio Sanitaria Sant Pere Claver (Spain), Spanish Mental Health Research Network (CIBERSAM), Barcelona, Spain. FAU - van Os, Jim AU - van Os J AD - Department of Psychiatry, UMC Utrecht Brain Centre, Utrecht, The Netherlands. AD - Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Mental Health Research and Teaching Network, Maastricht University Medical Centre, P.O. Box 616, 6200 MD 464, Maastricht, The Netherlands. FAU - Rutten, Bart P F AU - Rutten BPF AUID- ORCID: 0000-0002-9834-6346 AD - Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Mental Health Research and Teaching Network, Maastricht University Medical Centre, P.O. Box 616, 6200 MD 464, Maastricht, The Netherlands. FAU - Bressan, Rodrigo A AU - Bressan RA AD - PRISMA Clinic, Y-MIND-Institute for Prevention of Mental Disorders (PRISMA); LiNC-Lab Interdisciplinar Neurociencias Clinicas, Escola Paulista de Medicina, Universidade Federal de Sao Paulo-UNIFESP, Sao Paulo, Brazil. FAU - van der Gaag, Mark AU - van der Gaag M AUID- ORCID: 0000-0002-3525-6415 AD - VU University, Faculty of Behavioural and Movement Sciences, Department of Clinical Psychology and Amsterdam Public Mental Health research institute, van der Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands. FAU - Yolken, Robert AU - Yolken R AD - Stanley Neurovirology Division. Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, MD, USA. FAU - Hotopf, Matthew AU - Hotopf M AD - Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. FAU - Valmaggia, Lucia AU - Valmaggia L AD - Department of Psychology, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. FAU - Stone, James AU - Stone J AUID- ORCID: 0000-0003-3051-0135 AD - Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's Health Partners, King's College London, London, UK. AD - Precision Psychiatry Cluster, National Institute for Health Research Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London, London, UK. AD - South London and Maudsley NHS Foundation Trust, London, UK. AD - Department of Neuroimaging, Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. FAU - David, Anthony S AU - David AS AD - Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's Health Partners, King's College London, London, UK. AD - Institute of Mental Health, University College London, Maple House, 149 Tottenham Court Road, London, W1T 7NF, UK. CN - EUGEI High-Risk Study FAU - McGuire, Philip AU - McGuire P AD - Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's Health Partners, King's College London, London, UK. AD - Precision Psychiatry Cluster, National Institute for Health Research Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London, London, UK. AD - South London and Maudsley NHS Foundation Trust, London, UK. LA - eng GR - MR/J008915/1/MRC_/Medical Research Council/United Kingdom GR - 104079/Z/14/Z/Wellcome Trust (Wellcome)/ GR - WT_/Wellcome Trust/United Kingdom GR - 105758/Z/14/Z/WT_/Wellcome Trust/United Kingdom GR - DH_/Department of Health/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201019 PL - England TA - Mol Psychiatry JT - Molecular psychiatry JID - 9607835 RN - 0 (Autoantibodies) RN - 0 (Receptors, N-Methyl-D-Aspartate) SB - IM CIN - Mol Psychiatry. 2021 Jun;26(6):1723-1725. PMID: 32968237 MH - Animals MH - Autoantibodies MH - Case-Control Studies MH - Cognition MH - Humans MH - *Psychotic Disorders MH - *Receptors, N-Methyl-D-Aspartate PMC - PMC8440194 COIS- Dr. Pollak was supported by a clinical research training fellowship grant from the Wellcome Trust (no 105758/Z/14/Z). The European Network of National Schizophrenia Networks Studying Gene- Environment Interactions (EU-GEI) Project is funded by grant agreement HEALTH-F2-2010-241909 (Project EU-GEI) from the European Community's Seventh Framework Programme. Additional support was provided by a Medical Research Council Fellowship to M Kempton (grant MR/J008915/1). Dr. Irani is supported by a Wellcome Trust Intermediate Fellowship (104079/Z/14/Z), the British Medical Association Research Grants: Vera Down (2013) and Margaret Temple (2017). Dr. Nelson was supported by a NHMRC Senior Research Fellowship. Dr. Glenthoj is the leader of a Lundbeck Foundation Centre of Excellence for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), which is partially financed by an independent grant from the Lundbeck Foundation based on international review and partially financed by the Mental Health Services in the Capital Region of Denmark, the University of Copenhagen, and other foundations. Her group has also received a research grant from Lundbeck A/S for another independent investigator-initiated study. All grants are the property of the Mental Health Services in the Capital Region of Denmark and administrated by them. She has no other conflicts to disclose. Dr. De Haan has no conflicts to disclose. Dr. Ruhrmann is a project consultant of Boehringer Ingelheim. Bart PF Rutten is funded by a VIDI award number 91718336 from the Netherlands Scientific Organisation. Barnaby Nelson was supported by an NHMRC Senior Research Fellowship (1137687). ASD is supported by the NIHR University College London Hospital (UCLH) Biomedical Research Centre. Dr. Barrantes-Vidal was supported by the Ministerio de Ciencia, Innovacion e Universidades (PSI2017-87512-C2-1-R), Generalitat de Catalunya (2017SGR1612 and ICREA Academia Award). Dr Bressan has received research grants from Janssen and the governmental funding research agencies: CAPES, CNPq and FAPESP (2016/022465 and 2011/50740-5) and has participated in speaker bureaus for Janssen and Sanofi-Aventis, all outside the submitted work. The authors acknowledge financial support from the National Institute for Health Research (NIHR) Biomedical Research Centres at the South London and Maudsley NHS Foundation Trust, University College London Hospital and the John Radcliffe Hospital NHS Foundation Trust, Oxford. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. Additional support was provided by the Maudsley Charity (Grant Ref. 980) and Guy's and St. Thomas's Charity (Grant Ref. STR130505). These funders had no involvement in study design, data collection, analysis or the decision to submit for publication. The study received financial support by French Government's Agence Nationale pour la Recherche (ANR, 08-MNP-007) and by the French Health Ministry's Programme Hospitalier de Recherche Clinique (PHRC, AOM-07-118, 'Influence of cannabis psychopathological outcome in At risk mental state' (ICAAR study)). The Sainte-Anne hospital center promoted the study. Additional financial support was obtained from the Institut National de la Sante et de la Recherche Medicale (INSERM, recurrent funding and fellowships) and by Fondation Pierre Deniker. AV and SRI are coapplicants and receive royalties on patent application WO/2010/046716 (U.K. patent no., PCT/GB2009/051441) entitled 'Neurological Autoimmune Disorders'. The patent has been licensed to Euroimmun AG for the development of assays for LGI1 and other VGKC-complex antibodies. MOK participated on boards (Roche, Janssen) and received financial support from Janssen, Otsuka Lundbeck alliance, EIsai for conference or dissemination initiatives. FIR - Calem, Maria IR - Calem M FIR - Tognin, Stefania IR - Tognin S FIR - Modinos, Gemma IR - Modinos G FIR - de Haan, Lieuwe IR - de Haan L FIR - van der Gaag, Mark IR - van der Gaag M FIR - Velthorst, Eva IR - Velthorst E FIR - Kraan, Tamar C IR - Kraan TC FIR - van Dam, Daniella S IR - van Dam DS FIR - Burger, Nadine IR - Burger N FIR - Nelson, Barnaby IR - Nelson B FIR - McGorry, Patrick IR - McGorry P FIR - Pantelis, Christos IR - Pantelis C FIR - Politis, Athena IR - Politis A FIR - Goodall, Joanne IR - Goodall J FIR - Borgwardt, Stefan IR - Borgwardt S FIR - Ittig, Sarah IR - Ittig S FIR - Studerus, Erich IR - Studerus E FIR - Smieskova, Renata IR - Smieskova R FIR - Gadelha, Ary IR - Gadelha A FIR - Brietzke, Elisa IR - Brietzke E FIR - Asevedo, Graccielle IR - Asevedo G FIR - Asevedo, Elson IR - Asevedo E FIR - Zugman, Andre IR - Zugman A FIR - Rosa, Araceli IR - Rosa A FIR - Racioppi, Anna IR - Racioppi A FIR - Monsonet, Manel IR - Monsonet M FIR - Hinojosa-Marques, Lidia IR - Hinojosa-Marques L FIR - Kwapil, Thomas R IR - Kwapil TR FIR - Kazes, Mathilde IR - Kazes M FIR - Daban, Claire IR - Daban C FIR - Bourgin, Julie IR - Bourgin J FIR - Gay, Olivier IR - Gay O FIR - Mam-Lam-Fook, Celia IR - Mam-Lam-Fook C FIR - Nordholm, Dorte IR - Nordholm D FIR - Randers, Lasse IR - Randers L FIR - Krakauer, Kristine IR - Krakauer K FIR - Glenthoj, Louise IR - Glenthoj L FIR - Nordentoft, Merete IR - Nordentoft M FIR - Gebhard, Dominika IR - Gebhard D FIR - Arnhold, Julia IR - Arnhold J FIR - Klosterkotter, Joachim IR - Klosterkotter J FIR - Lasser, Iris IR - Lasser I FIR - Winklbaur, Bernadette IR - Winklbaur B FIR - Delespaul, Philippe A IR - Delespaul PA FIR - van Os, Jim IR - van Os J EDAT- 2020/10/21 06:00 MHDA- 2021/10/12 06:00 PMCR- 2020/10/19 CRDT- 2020/10/20 06:21 PHST- 2019/04/21 00:00 [received] PHST- 2020/09/21 00:00 [accepted] PHST- 2020/07/28 00:00 [revised] PHST- 2020/10/21 06:00 [pubmed] PHST- 2021/10/12 06:00 [medline] PHST- 2020/10/20 06:21 [entrez] PHST- 2020/10/19 00:00 [pmc-release] AID - 10.1038/s41380-020-00899-w [pii] AID - 899 [pii] AID - 10.1038/s41380-020-00899-w [doi] PST - ppublish SO - Mol Psychiatry. 2021 Jun;26(6):2590-2604. doi: 10.1038/s41380-020-00899-w. Epub 2020 Oct 19.