Clinical, cognitive and neuroanatomical associations of serum NMDAR autoantibodies in people at clinical high risk for psychosis.
Identifieur interne : 000052 ( Main/Corpus ); précédent : 000051; suivant : 000053Clinical, cognitive and neuroanatomical associations of serum NMDAR autoantibodies in people at clinical high risk for psychosis.
Auteurs : Thomas A. Pollak ; Matthew J. Kempton ; Conrad Iyegbe ; Angela Vincent ; Sarosh R. Irani ; Ester Coutinho ; David A. Menassa ; Leslie Jacobson ; Lieuwe De Haan ; Stephan Ruhrmann ; Gabriele Sachs ; Anita Riecher-Rössler ; Marie-Odile Krebs ; Paul Amminger ; Birte Glenth J ; Neus Barrantes-Vidal ; Jim Van Os ; Bart P F. Rutten ; Rodrigo A. Bressan ; Mark Van Der Gaag ; Robert Yolken ; Matthew Hotopf ; Lucia Valmaggia ; James Stone ; Anthony S. David ; Philip McguireSource :
- Molecular psychiatry [ 1476-5578 ] ; 2020.
Abstract
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.
DOI: 10.1038/s41380-020-00899-w
PubMed: 33077853
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Clinical, cognitive and neuroanatomical associations of serum NMDAR autoantibodies in people at clinical high risk for psychosis.</title><author><name sortKey="Pollak, Thomas A" sort="Pollak, Thomas A" uniqKey="Pollak T" first="Thomas A" last="Pollak">Thomas A. Pollak</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>South London and Maudsley NHS Foundation Trust, London, UK. thomas.pollak@kcl.ac.uk.</nlm:affiliation></affiliation></author><author><name sortKey="Kempton, Matthew J" sort="Kempton, Matthew J" uniqKey="Kempton M" first="Matthew J" last="Kempton">Matthew J. Kempton</name><affiliation><nlm:affiliation>Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's Health Partners, King's College London, London, UK.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Iyegbe, Conrad" sort="Iyegbe, Conrad" uniqKey="Iyegbe C" first="Conrad" last="Iyegbe">Conrad Iyegbe</name><affiliation><nlm:affiliation>Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's Health Partners, King's College London, London, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Vincent, Angela" sort="Vincent, Angela" uniqKey="Vincent A" first="Angela" last="Vincent">Angela Vincent</name><affiliation><nlm:affiliation>Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Irani, Sarosh R" sort="Irani, Sarosh R" uniqKey="Irani S" first="Sarosh R" last="Irani">Sarosh R. Irani</name><affiliation><nlm:affiliation>Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Coutinho, Ester" sort="Coutinho, Ester" uniqKey="Coutinho E" first="Ester" last="Coutinho">Ester Coutinho</name><affiliation><nlm:affiliation>Division of Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's Health Partners, King's College London, London, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Menassa, David A" sort="Menassa, David A" uniqKey="Menassa D" first="David A" last="Menassa">David A. Menassa</name><affiliation><nlm:affiliation>Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, UK.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Biological Sciences, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Jacobson, Leslie" sort="Jacobson, Leslie" uniqKey="Jacobson L" first="Leslie" last="Jacobson">Leslie Jacobson</name><affiliation><nlm:affiliation>Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, UK.</nlm:affiliation></affiliation></author><author><name sortKey="De Haan, Lieuwe" sort="De Haan, Lieuwe" uniqKey="De Haan L" first="Lieuwe" last="De Haan">Lieuwe De Haan</name><affiliation><nlm:affiliation>Amsterdam UMC, University of Amsterdam, Psychiatry, Department Early Psychosis, Meibergdreef 9, Amsterdam, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Ruhrmann, Stephan" sort="Ruhrmann, Stephan" uniqKey="Ruhrmann S" first="Stephan" last="Ruhrmann">Stephan Ruhrmann</name><affiliation><nlm:affiliation>Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital, University of Cologne, Cologne, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Sachs, Gabriele" sort="Sachs, Gabriele" uniqKey="Sachs G" first="Gabriele" last="Sachs">Gabriele Sachs</name><affiliation><nlm:affiliation>Medical University of Vienna, Department of Psychiatry and Psychotherapy, Vienna, Austria.</nlm:affiliation></affiliation></author><author><name sortKey="Riecher Rossler, Anita" sort="Riecher Rossler, Anita" uniqKey="Riecher Rossler A" first="Anita" last="Riecher-Rössler">Anita Riecher-Rössler</name><affiliation><nlm:affiliation>Medical Faculty, University of Basel, Basel, Switzerland.</nlm:affiliation></affiliation></author><author><name sortKey="Krebs, Marie Odile" sort="Krebs, Marie Odile" uniqKey="Krebs M" first="Marie-Odile" last="Krebs">Marie-Odile Krebs</name><affiliation><nlm:affiliation>University of Paris, GHU-Paris, Sainte-Anne, C'JAAD, Hospitalo-Universitaire department SHU, Inserm U1266, Institut de Psychiatrie (CNRS 3557), Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Amminger, Paul" sort="Amminger, Paul" uniqKey="Amminger P" first="Paul" last="Amminger">Paul Amminger</name><affiliation><nlm:affiliation>Centre for Youth Mental Health, University of Melbourne, 35 Poplar Road (Locked Bag 10), Parkville, VIC, 4853052, Australia.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Orygen, The National Centre of Excellence in Youth Mental Health, The University of Melbourne, Parkville, VIC, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Glenth J, Birte" sort="Glenth J, Birte" uniqKey="Glenth J B" first="Birte" last="Glenth J">Birte Glenth J</name><affiliation><nlm:affiliation>Centre for Neuropsychiatric Schizophrenia Research (CNSR) & Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="Barrantes Vidal, Neus" sort="Barrantes Vidal, Neus" uniqKey="Barrantes Vidal N" first="Neus" last="Barrantes-Vidal">Neus Barrantes-Vidal</name><affiliation><nlm:affiliation>Departament de Psicologia Clínica I de la Salut (Universitat Autònoma de Barcelona), Fundació Sanitària Sant Pere Claver (Spain), Spanish Mental Health Research Network (CIBERSAM), Barcelona, Spain.</nlm:affiliation></affiliation></author><author><name sortKey="Van Os, Jim" sort="Van Os, Jim" uniqKey="Van Os J" first="Jim" last="Van Os">Jim Van Os</name><affiliation><nlm:affiliation>Department of Psychiatry, UMC Utrecht Brain Centre, Utrecht, The Netherlands.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Rutten, Bart P F" sort="Rutten, Bart P F" uniqKey="Rutten B" first="Bart P F" last="Rutten">Bart P F. Rutten</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Bressan, Rodrigo A" sort="Bressan, Rodrigo A" uniqKey="Bressan R" first="Rodrigo A" last="Bressan">Rodrigo A. Bressan</name><affiliation><nlm:affiliation>PRISMA Clinic, Y-MIND-Institute for Prevention of Mental Disorders (PRISMA); LiNC-Lab Interdisciplinar Neurociências Clínicas, Escola Paulista de Medicina, Universidade Federal de São Paulo-UNIFESP, Sao Paulo, Brazil.</nlm:affiliation></affiliation></author><author><name sortKey="Van Der Gaag, Mark" sort="Van Der Gaag, Mark" uniqKey="Van Der Gaag M" first="Mark" last="Van Der Gaag">Mark Van Der Gaag</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Yolken, Robert" sort="Yolken, Robert" uniqKey="Yolken R" first="Robert" last="Yolken">Robert Yolken</name><affiliation><nlm:affiliation>Stanley Neurovirology Division. Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, MD, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Hotopf, Matthew" sort="Hotopf, Matthew" uniqKey="Hotopf M" first="Matthew" last="Hotopf">Matthew Hotopf</name><affiliation><nlm:affiliation>Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Valmaggia, Lucia" sort="Valmaggia, Lucia" uniqKey="Valmaggia L" first="Lucia" last="Valmaggia">Lucia Valmaggia</name><affiliation><nlm:affiliation>Department of Psychology, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Stone, James" sort="Stone, James" uniqKey="Stone J" first="James" last="Stone">James Stone</name><affiliation><nlm:affiliation>Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's Health Partners, King's College London, London, UK.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>South London and Maudsley NHS Foundation Trust, London, UK.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Department of Neuroimaging, Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.</nlm:affiliation></affiliation></author><author><name sortKey="David, Anthony S" sort="David, Anthony S" uniqKey="David A" first="Anthony S" last="David">Anthony S. David</name><affiliation><nlm:affiliation>Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's Health Partners, King's College London, London, UK.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Institute of Mental Health, University College London, Maple House, 149 Tottenham Court Road, London, W1T 7NF, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Mcguire, Philip" sort="Mcguire, Philip" uniqKey="Mcguire P" first="Philip" last="Mcguire">Philip Mcguire</name><affiliation><nlm:affiliation>Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's Health Partners, King's College London, London, UK.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>South London and Maudsley NHS Foundation Trust, London, UK.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:33077853</idno><idno type="pmid">33077853</idno><idno type="doi">10.1038/s41380-020-00899-w</idno><idno type="wicri:Area/Main/Corpus">000052</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000052</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Clinical, cognitive and neuroanatomical associations of serum NMDAR autoantibodies in people at clinical high risk for psychosis.</title><author><name sortKey="Pollak, Thomas A" sort="Pollak, Thomas A" uniqKey="Pollak T" first="Thomas A" last="Pollak">Thomas A. Pollak</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>South London and Maudsley NHS Foundation Trust, London, UK. thomas.pollak@kcl.ac.uk.</nlm:affiliation></affiliation></author><author><name sortKey="Kempton, Matthew J" sort="Kempton, Matthew J" uniqKey="Kempton M" first="Matthew J" last="Kempton">Matthew J. Kempton</name><affiliation><nlm:affiliation>Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's Health Partners, King's College London, London, UK.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Iyegbe, Conrad" sort="Iyegbe, Conrad" uniqKey="Iyegbe C" first="Conrad" last="Iyegbe">Conrad Iyegbe</name><affiliation><nlm:affiliation>Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's Health Partners, King's College London, London, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Vincent, Angela" sort="Vincent, Angela" uniqKey="Vincent A" first="Angela" last="Vincent">Angela Vincent</name><affiliation><nlm:affiliation>Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Irani, Sarosh R" sort="Irani, Sarosh R" uniqKey="Irani S" first="Sarosh R" last="Irani">Sarosh R. Irani</name><affiliation><nlm:affiliation>Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Coutinho, Ester" sort="Coutinho, Ester" uniqKey="Coutinho E" first="Ester" last="Coutinho">Ester Coutinho</name><affiliation><nlm:affiliation>Division of Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's Health Partners, King's College London, London, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Menassa, David A" sort="Menassa, David A" uniqKey="Menassa D" first="David A" last="Menassa">David A. Menassa</name><affiliation><nlm:affiliation>Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, UK.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Biological Sciences, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Jacobson, Leslie" sort="Jacobson, Leslie" uniqKey="Jacobson L" first="Leslie" last="Jacobson">Leslie Jacobson</name><affiliation><nlm:affiliation>Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, UK.</nlm:affiliation></affiliation></author><author><name sortKey="De Haan, Lieuwe" sort="De Haan, Lieuwe" uniqKey="De Haan L" first="Lieuwe" last="De Haan">Lieuwe De Haan</name><affiliation><nlm:affiliation>Amsterdam UMC, University of Amsterdam, Psychiatry, Department Early Psychosis, Meibergdreef 9, Amsterdam, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Ruhrmann, Stephan" sort="Ruhrmann, Stephan" uniqKey="Ruhrmann S" first="Stephan" last="Ruhrmann">Stephan Ruhrmann</name><affiliation><nlm:affiliation>Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital, University of Cologne, Cologne, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Sachs, Gabriele" sort="Sachs, Gabriele" uniqKey="Sachs G" first="Gabriele" last="Sachs">Gabriele Sachs</name><affiliation><nlm:affiliation>Medical University of Vienna, Department of Psychiatry and Psychotherapy, Vienna, Austria.</nlm:affiliation></affiliation></author><author><name sortKey="Riecher Rossler, Anita" sort="Riecher Rossler, Anita" uniqKey="Riecher Rossler A" first="Anita" last="Riecher-Rössler">Anita Riecher-Rössler</name><affiliation><nlm:affiliation>Medical Faculty, University of Basel, Basel, Switzerland.</nlm:affiliation></affiliation></author><author><name sortKey="Krebs, Marie Odile" sort="Krebs, Marie Odile" uniqKey="Krebs M" first="Marie-Odile" last="Krebs">Marie-Odile Krebs</name><affiliation><nlm:affiliation>University of Paris, GHU-Paris, Sainte-Anne, C'JAAD, Hospitalo-Universitaire department SHU, Inserm U1266, Institut de Psychiatrie (CNRS 3557), Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Amminger, Paul" sort="Amminger, Paul" uniqKey="Amminger P" first="Paul" last="Amminger">Paul Amminger</name><affiliation><nlm:affiliation>Centre for Youth Mental Health, University of Melbourne, 35 Poplar Road (Locked Bag 10), Parkville, VIC, 4853052, Australia.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Orygen, The National Centre of Excellence in Youth Mental Health, The University of Melbourne, Parkville, VIC, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Glenth J, Birte" sort="Glenth J, Birte" uniqKey="Glenth J B" first="Birte" last="Glenth J">Birte Glenth J</name><affiliation><nlm:affiliation>Centre for Neuropsychiatric Schizophrenia Research (CNSR) & Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="Barrantes Vidal, Neus" sort="Barrantes Vidal, Neus" uniqKey="Barrantes Vidal N" first="Neus" last="Barrantes-Vidal">Neus Barrantes-Vidal</name><affiliation><nlm:affiliation>Departament de Psicologia Clínica I de la Salut (Universitat Autònoma de Barcelona), Fundació Sanitària Sant Pere Claver (Spain), Spanish Mental Health Research Network (CIBERSAM), Barcelona, Spain.</nlm:affiliation></affiliation></author><author><name sortKey="Van Os, Jim" sort="Van Os, Jim" uniqKey="Van Os J" first="Jim" last="Van Os">Jim Van Os</name><affiliation><nlm:affiliation>Department of Psychiatry, UMC Utrecht Brain Centre, Utrecht, The Netherlands.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Rutten, Bart P F" sort="Rutten, Bart P F" uniqKey="Rutten B" first="Bart P F" last="Rutten">Bart P F. Rutten</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Bressan, Rodrigo A" sort="Bressan, Rodrigo A" uniqKey="Bressan R" first="Rodrigo A" last="Bressan">Rodrigo A. Bressan</name><affiliation><nlm:affiliation>PRISMA Clinic, Y-MIND-Institute for Prevention of Mental Disorders (PRISMA); LiNC-Lab Interdisciplinar Neurociências Clínicas, Escola Paulista de Medicina, Universidade Federal de São Paulo-UNIFESP, Sao Paulo, Brazil.</nlm:affiliation></affiliation></author><author><name sortKey="Van Der Gaag, Mark" sort="Van Der Gaag, Mark" uniqKey="Van Der Gaag M" first="Mark" last="Van Der Gaag">Mark Van Der Gaag</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Yolken, Robert" sort="Yolken, Robert" uniqKey="Yolken R" first="Robert" last="Yolken">Robert Yolken</name><affiliation><nlm:affiliation>Stanley Neurovirology Division. Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, MD, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Hotopf, Matthew" sort="Hotopf, Matthew" uniqKey="Hotopf M" first="Matthew" last="Hotopf">Matthew Hotopf</name><affiliation><nlm:affiliation>Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Valmaggia, Lucia" sort="Valmaggia, Lucia" uniqKey="Valmaggia L" first="Lucia" last="Valmaggia">Lucia Valmaggia</name><affiliation><nlm:affiliation>Department of Psychology, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Stone, James" sort="Stone, James" uniqKey="Stone J" first="James" last="Stone">James Stone</name><affiliation><nlm:affiliation>Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's Health Partners, King's College London, London, UK.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>South London and Maudsley NHS Foundation Trust, London, UK.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Department of Neuroimaging, Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.</nlm:affiliation></affiliation></author><author><name sortKey="David, Anthony S" sort="David, Anthony S" uniqKey="David A" first="Anthony S" last="David">Anthony S. David</name><affiliation><nlm:affiliation>Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's Health Partners, King's College London, London, UK.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Institute of Mental Health, University College London, Maple House, 149 Tottenham Court Road, London, W1T 7NF, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Mcguire, Philip" sort="Mcguire, Philip" uniqKey="Mcguire P" first="Philip" last="Mcguire">Philip Mcguire</name><affiliation><nlm:affiliation>Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's Health Partners, King's College London, London, UK.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>South London and Maudsley NHS Foundation Trust, London, UK.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Molecular psychiatry</title><idno type="eISSN">1476-5578</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><pubmed><MedlineCitation Status="Publisher" Owner="NLM"><PMID Version="1">33077853</PMID><DateRevised><Year>2020</Year><Month>10</Month><Day>20</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1476-5578</ISSN><JournalIssue CitedMedium="Internet"><PubDate><Year>2020</Year><Month>Oct</Month><Day>19</Day></PubDate></JournalIssue><Title>Molecular psychiatry</Title><ISOAbbreviation>Mol Psychiatry</ISOAbbreviation></Journal><ArticleTitle>Clinical, cognitive and neuroanatomical associations of serum NMDAR autoantibodies in people at clinical high risk for psychosis.</ArticleTitle><ELocationID EIdType="doi" ValidYN="Y">10.1038/s41380-020-00899-w</ELocationID><Abstract><AbstractText>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.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Pollak</LastName><ForeName>Thomas A</ForeName><Initials>TA</Initials><Identifier Source="ORCID">http://orcid.org/0000-0002-6171-0810</Identifier><AffiliationInfo><Affiliation>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.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>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.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>South London and Maudsley NHS Foundation Trust, London, UK. thomas.pollak@kcl.ac.uk.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kempton</LastName><ForeName>Matthew J</ForeName><Initials>MJ</Initials><AffiliationInfo><Affiliation>Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's Health Partners, King's College London, London, UK.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Iyegbe</LastName><ForeName>Conrad</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's Health Partners, King's College London, London, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Vincent</LastName><ForeName>Angela</ForeName><Initials>A</Initials><Identifier Source="ORCID">http://orcid.org/0000-0003-2395-8695</Identifier><AffiliationInfo><Affiliation>Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Irani</LastName><ForeName>Sarosh R</ForeName><Initials>SR</Initials><AffiliationInfo><Affiliation>Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Coutinho</LastName><ForeName>Ester</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Division of Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's Health Partners, King's College London, London, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Menassa</LastName><ForeName>David A</ForeName><Initials>DA</Initials><AffiliationInfo><Affiliation>Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, UK.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Biological Sciences, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jacobson</LastName><ForeName>Leslie</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>de Haan</LastName><ForeName>Lieuwe</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Amsterdam UMC, University of Amsterdam, Psychiatry, Department Early Psychosis, Meibergdreef 9, Amsterdam, The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ruhrmann</LastName><ForeName>Stephan</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital, University of Cologne, Cologne, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sachs</LastName><ForeName>Gabriele</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Medical University of Vienna, Department of Psychiatry and Psychotherapy, Vienna, Austria.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Riecher-Rössler</LastName><ForeName>Anita</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Medical Faculty, University of Basel, Basel, Switzerland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Krebs</LastName><ForeName>Marie-Odile</ForeName><Initials>MO</Initials><AffiliationInfo><Affiliation>University of Paris, GHU-Paris, Sainte-Anne, C'JAAD, Hospitalo-Universitaire department SHU, Inserm U1266, Institut de Psychiatrie (CNRS 3557), Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Amminger</LastName><ForeName>Paul</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Centre for Youth Mental Health, University of Melbourne, 35 Poplar Road (Locked Bag 10), Parkville, VIC, 4853052, Australia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Orygen, The National Centre of Excellence in Youth Mental Health, The University of Melbourne, Parkville, VIC, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Glenthøj</LastName><ForeName>Birte</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Centre for Neuropsychiatric Schizophrenia Research (CNSR) & Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Barrantes-Vidal</LastName><ForeName>Neus</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Departament de Psicologia Clínica I de la Salut (Universitat Autònoma de Barcelona), Fundació Sanitària Sant Pere Claver (Spain), Spanish Mental Health Research Network (CIBERSAM), Barcelona, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>van Os</LastName><ForeName>Jim</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Psychiatry, UMC Utrecht Brain Centre, Utrecht, The Netherlands.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rutten</LastName><ForeName>Bart P F</ForeName><Initials>BPF</Initials><Identifier Source="ORCID">http://orcid.org/0000-0002-9834-6346</Identifier><AffiliationInfo><Affiliation>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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bressan</LastName><ForeName>Rodrigo A</ForeName><Initials>RA</Initials><AffiliationInfo><Affiliation>PRISMA Clinic, Y-MIND-Institute for Prevention of Mental Disorders (PRISMA); LiNC-Lab Interdisciplinar Neurociências Clínicas, Escola Paulista de Medicina, Universidade Federal de São Paulo-UNIFESP, Sao Paulo, Brazil.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>van der Gaag</LastName><ForeName>Mark</ForeName><Initials>M</Initials><Identifier Source="ORCID">http://orcid.org/0000-0002-3525-6415</Identifier><AffiliationInfo><Affiliation>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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yolken</LastName><ForeName>Robert</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Stanley Neurovirology Division. Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, MD, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hotopf</LastName><ForeName>Matthew</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Valmaggia</LastName><ForeName>Lucia</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Psychology, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Stone</LastName><ForeName>James</ForeName><Initials>J</Initials><Identifier Source="ORCID">http://orcid.org/0000-0003-3051-0135</Identifier><AffiliationInfo><Affiliation>Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's Health Partners, King's College London, London, UK.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>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.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>South London and Maudsley NHS Foundation Trust, London, UK.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Neuroimaging, Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>David</LastName><ForeName>Anthony S</ForeName><Initials>AS</Initials><AffiliationInfo><Affiliation>Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's Health Partners, King's College London, London, UK.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Mental Health, University College London, Maple House, 149 Tottenham Court Road, London, W1T 7NF, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><CollectiveName>EUGEI High-Risk Study</CollectiveName></Author><Author ValidYN="Y"><LastName>McGuire</LastName><ForeName>Philip</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's Health Partners, King's College London, London, UK.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>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.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>South London and Maudsley NHS Foundation Trust, London, UK.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>MR/J008915/1</GrantID><Agency>RCUK | Medical Research Council (MRC)</Agency><Country></Country></Grant><Grant><GrantID>104079/Z/14/Z</GrantID><Agency>Wellcome Trust (Wellcome)</Agency><Country></Country></Grant><Grant><GrantID>08-MNP-007</GrantID><Agency>Agence Nationale de la Recherche (French National Research Agency)</Agency><Country></Country></Grant><Grant><GrantID>2017SGR1612</GrantID><Agency>Generalitat de Catalunya (Government of Catalonia)</Agency><Country></Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>10</Month><Day>19</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Mol 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