Depressive symptoms and anti-N-methyl-D-aspartate-receptor GluN1 antibody seropositivity in the PROSpective cohort with incident stroke

Background: Anti-NMDA-receptor GluN1 antibodies (NMDAR1-abs) are present in an autoimmune encephalitis with severe neuropsychiatric symptoms. We aimed to estimate the impact of serum NMDAR1-abs on depressive symptoms years after first-ever ischemic stroke (IS). Methods: Data were used from the PROSp...

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Main Authors: Pia S. Sperber, Pimrapat Gebert, Leonie H.A. Broersen, Anna Kufner, Shufan Huo, Sophie K. Piper, Bianca Teegen, Peter U. Heuschmann, Harald Prüss, Matthias Endres, Thomas G. Liman, Bob Siegerink
Format: Article
Language:English
Published: Elsevier 2023-12-01
Series:Brain, Behavior, & Immunity - Health
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Online Access:http://www.sciencedirect.com/science/article/pii/S2666354623001199
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author Pia S. Sperber
Pimrapat Gebert
Leonie H.A. Broersen
Anna Kufner
Shufan Huo
Sophie K. Piper
Bianca Teegen
Peter U. Heuschmann
Harald Prüss
Matthias Endres
Thomas G. Liman
Bob Siegerink
author_facet Pia S. Sperber
Pimrapat Gebert
Leonie H.A. Broersen
Anna Kufner
Shufan Huo
Sophie K. Piper
Bianca Teegen
Peter U. Heuschmann
Harald Prüss
Matthias Endres
Thomas G. Liman
Bob Siegerink
author_sort Pia S. Sperber
collection DOAJ
description Background: Anti-NMDA-receptor GluN1 antibodies (NMDAR1-abs) are present in an autoimmune encephalitis with severe neuropsychiatric symptoms. We aimed to estimate the impact of serum NMDAR1-abs on depressive symptoms years after first-ever ischemic stroke (IS). Methods: Data were used from the PROSpective Cohort with Incident Stroke-Berlin (PROSCIS-B; NCT01363856). Serum NMDAR1-abs (IgM/IgA/IgG) were measured within 7 days after IS using cell-based assays. We defined seropositivity as titers ≥1:10, thereof low titers as ≤1:100 and high titers as >1:100. We used the Center for Epidemiological Studies–Depression (CES-D) scale to measure depressive symptoms at year one, two and three following IS. We calculated crude and confounder adjusted weighted generalized linear models to quantify the impact of NMDAR1-abs on CES-D assessed at three annual time-points. Results: NMDAR1-abs were measured in 583 PROSCIS-B IS patients (mean age = 67 [SD = 13]; 42%female; median NIHSS = 2 [IQR = 1–4]) of whom 76 (13%; IgM: n = 49/IgA: n = 43/IgG: n = 2) were seropositive, 55 (9%) with low and 21 (4%) with high titers. CES-D regarded over all follow-up time-points was higher in seropositive patients (βcrude = 2.56 [95%CI = −0.34 to 5.45]; βadjusted = 2.26 [95%CI = −0.68 to 5.20]) and effects were highest in patients with high titer (low titers: βcrude = 1.42 [95%CI = −1.79 to 4.62], βadjusted = 0.53 [95%CI = −2.47 to 3.54]; high titers: βcrude = 5.85 [95%CI = 0.20 to 11.50]; βadjusted = 7.20 [95%CI = 0.98 to 13.43]). Conclusion: Patients with serum NMDAR1-abs (predominantly IgM&IgA) suffer more severe depressive symptoms after mild-to-moderate IS compared to NMDAR1-abs seronegative patients.
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spelling doaj.art-4d0c1842851e4139958eeef248ef2aff2023-12-03T05:43:07ZengElsevierBrain, Behavior, & Immunity - Health2666-35462023-12-0134100705Depressive symptoms and anti-N-methyl-D-aspartate-receptor GluN1 antibody seropositivity in the PROSpective cohort with incident strokePia S. Sperber0Pimrapat Gebert1Leonie H.A. Broersen2Anna Kufner3Shufan Huo4Sophie K. Piper5Bianca Teegen6Peter U. Heuschmann7Harald Prüss8Matthias Endres9Thomas G. Liman10Bob Siegerink11Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, And Berlin Institute of Health, Center for Stroke Research Berlin (CSB), Berlin, Germany; German Centre for Cardiovascular Research DZHK, Partner Site, Berlin, Germany; Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, And Berlin Institute of Health, Department of Neurology with Experimental Neurology, Berlin, Germany; Charité – Universitätsmedizin Berlin & Max Delbrück Center for Molecular Medicine, Experimental and Clinical Research Center (ECRC), Berlin, Germany; Corresponding author. Center for Stroke Research Berlin (CSB), Charité – Universitätsmedizin Berlin, Charitéplatz 1, D-10117, Berlin, Germany.Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, And Berlin Institute of Health, Institute of Biometry and Clinical Epidemiology, Berlin, Germany; Berlin Institute of Health (BIH), Charité – Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, GermanyCharité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, And Berlin Institute of Health, Center for Stroke Research Berlin (CSB), Berlin, GermanyCharité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, And Berlin Institute of Health, Center for Stroke Research Berlin (CSB), Berlin, Germany; Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, And Berlin Institute of Health, Department of Neurology with Experimental Neurology, Berlin, GermanyCharité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, And Berlin Institute of Health, Center for Stroke Research Berlin (CSB), Berlin, Germany; German Centre for Cardiovascular Research DZHK, Partner Site, Berlin, Germany; Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, And Berlin Institute of Health, Department of Neurology with Experimental Neurology, Berlin, Germany; Charité – Universitätsmedizin Berlin & Max Delbrück Center for Molecular Medicine, Experimental and Clinical Research Center (ECRC), Berlin, GermanyCharité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, And Berlin Institute of Health, Institute of Biometry and Clinical Epidemiology, Berlin, Germany; Berlin Institute of Health (BIH), Charité – Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany; Charité – Universitätsmedizin Berlin Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, And Berlin Institute of Health, Institute of Medical Informatics, GermanyInstitute of Experimental Immunology, EUROIMMUN AG, Luebeck, GermanyUniversity of Würzburg, Institute of Clinical Epidemiology and Biometry, Würzburg, Germany; University Hospital Würzburg, Clinical Trial Center Würzburg, Würzburg, GermanyCharité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, And Berlin Institute of Health, Department of Neurology with Experimental Neurology, Berlin, Germany; German Center for Neurodegenerative Disease DZNE, Partner Site, Berlin, GermanyCharité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, And Berlin Institute of Health, Center for Stroke Research Berlin (CSB), Berlin, Germany; German Centre for Cardiovascular Research DZHK, Partner Site, Berlin, Germany; Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, And Berlin Institute of Health, Department of Neurology with Experimental Neurology, Berlin, Germany; Charité – Universitätsmedizin Berlin & Max Delbrück Center for Molecular Medicine, Experimental and Clinical Research Center (ECRC), Berlin, Germany; German Center for Neurodegenerative Disease DZNE, Partner Site, Berlin, GermanyCharité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, And Berlin Institute of Health, Center for Stroke Research Berlin (CSB), Berlin, Germany; German Centre for Cardiovascular Research DZHK, Partner Site, Berlin, Germany; Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, And Berlin Institute of Health, Department of Neurology with Experimental Neurology, Berlin, Germany; Carl von Ossietzky-University, Evangelisches Krankenhaus Oldenburg, Department of Neurology, Oldenburg, GermanyCharité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, And Berlin Institute of Health, Center for Stroke Research Berlin (CSB), Berlin, Germany; Department of Clinical Epidemiology, Leiden University Medical Center, Leiden University, Leiden, the NetherlandsBackground: Anti-NMDA-receptor GluN1 antibodies (NMDAR1-abs) are present in an autoimmune encephalitis with severe neuropsychiatric symptoms. We aimed to estimate the impact of serum NMDAR1-abs on depressive symptoms years after first-ever ischemic stroke (IS). Methods: Data were used from the PROSpective Cohort with Incident Stroke-Berlin (PROSCIS-B; NCT01363856). Serum NMDAR1-abs (IgM/IgA/IgG) were measured within 7 days after IS using cell-based assays. We defined seropositivity as titers ≥1:10, thereof low titers as ≤1:100 and high titers as >1:100. We used the Center for Epidemiological Studies–Depression (CES-D) scale to measure depressive symptoms at year one, two and three following IS. We calculated crude and confounder adjusted weighted generalized linear models to quantify the impact of NMDAR1-abs on CES-D assessed at three annual time-points. Results: NMDAR1-abs were measured in 583 PROSCIS-B IS patients (mean age = 67 [SD = 13]; 42%female; median NIHSS = 2 [IQR = 1–4]) of whom 76 (13%; IgM: n = 49/IgA: n = 43/IgG: n = 2) were seropositive, 55 (9%) with low and 21 (4%) with high titers. CES-D regarded over all follow-up time-points was higher in seropositive patients (βcrude = 2.56 [95%CI = −0.34 to 5.45]; βadjusted = 2.26 [95%CI = −0.68 to 5.20]) and effects were highest in patients with high titer (low titers: βcrude = 1.42 [95%CI = −1.79 to 4.62], βadjusted = 0.53 [95%CI = −2.47 to 3.54]; high titers: βcrude = 5.85 [95%CI = 0.20 to 11.50]; βadjusted = 7.20 [95%CI = 0.98 to 13.43]). Conclusion: Patients with serum NMDAR1-abs (predominantly IgM&IgA) suffer more severe depressive symptoms after mild-to-moderate IS compared to NMDAR1-abs seronegative patients.http://www.sciencedirect.com/science/article/pii/S2666354623001199StrokeIschemiaProspective studiesReceptorsN-Methyl-D-AspartateAntibodies
spellingShingle Pia S. Sperber
Pimrapat Gebert
Leonie H.A. Broersen
Anna Kufner
Shufan Huo
Sophie K. Piper
Bianca Teegen
Peter U. Heuschmann
Harald Prüss
Matthias Endres
Thomas G. Liman
Bob Siegerink
Depressive symptoms and anti-N-methyl-D-aspartate-receptor GluN1 antibody seropositivity in the PROSpective cohort with incident stroke
Brain, Behavior, & Immunity - Health
Stroke
Ischemia
Prospective studies
Receptors
N-Methyl-D-Aspartate
Antibodies
title Depressive symptoms and anti-N-methyl-D-aspartate-receptor GluN1 antibody seropositivity in the PROSpective cohort with incident stroke
title_full Depressive symptoms and anti-N-methyl-D-aspartate-receptor GluN1 antibody seropositivity in the PROSpective cohort with incident stroke
title_fullStr Depressive symptoms and anti-N-methyl-D-aspartate-receptor GluN1 antibody seropositivity in the PROSpective cohort with incident stroke
title_full_unstemmed Depressive symptoms and anti-N-methyl-D-aspartate-receptor GluN1 antibody seropositivity in the PROSpective cohort with incident stroke
title_short Depressive symptoms and anti-N-methyl-D-aspartate-receptor GluN1 antibody seropositivity in the PROSpective cohort with incident stroke
title_sort depressive symptoms and anti n methyl d aspartate receptor glun1 antibody seropositivity in the prospective cohort with incident stroke
topic Stroke
Ischemia
Prospective studies
Receptors
N-Methyl-D-Aspartate
Antibodies
url http://www.sciencedirect.com/science/article/pii/S2666354623001199
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