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

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

Brain, Behavior, & Immunity - Health (Dec 2023)

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

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

Affiliations

Pia S. Sperber: Charité – 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.
Pimrapat Gebert: 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, Germany
Leonie H.A. Broersen: Charité – 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
Anna Kufner: Charité – 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, Germany
Shufan Huo: Charité – 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
Sophie K. Piper: 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, Germany; Charité – Universitätsmedizin Berlin Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, And Berlin Institute of Health, Institute of Medical Informatics, Germany
Bianca Teegen: Institute of Experimental Immunology, EUROIMMUN AG, Luebeck, Germany
Peter U. Heuschmann: University of Würzburg, Institute of Clinical Epidemiology and Biometry, Würzburg, Germany; University Hospital Würzburg, Clinical Trial Center Würzburg, Würzburg, Germany
Harald Prüss: 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; German Center for Neurodegenerative Disease DZNE, Partner Site, Berlin, Germany
Matthias Endres: Charité – 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, Germany
Thomas G. Liman: Charité – 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, Germany
Bob Siegerink: Charité – 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 Netherlands

Journal volume & issue: Vol. 34
p. 100705

Abstract

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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.

Published in Brain, Behavior, & Immunity - Health

ISSN: 2666-3546 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/brain-behavior-and-immunity-health

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