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A randomised clinical trial of methotrexate points to possible efficacy and adaptive immune dysfunction in psychosis

NMDA autoantibody encephalitis presenting as schizophrenia suggests the possible role of adaptive cell-mediated immunity in idiopathic schizophrenia. However, to our knowledge there have been no trials of the immune-suppressant methotrexate in schizophrenia. We tested if low-dose methotrexate as use...

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Autores principales: Chaudhry, I. B., Husain, M. O., Khoso, A. B., Husain, M. I., Buch, M. H., Kiran, T., Fu, B., Bassett, P., Qurashi, I., ur Rahman, R., Baig, S., Kazmi, A., Corsi-Zuelli, F., Haddad, P. M., Deakin, B., Husain, N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705702/
https://www.ncbi.nlm.nih.gov/pubmed/33257661
http://dx.doi.org/10.1038/s41398-020-01095-8
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author Chaudhry, I. B.
Husain, M. O.
Khoso, A. B.
Husain, M. I.
Buch, M. H.
Kiran, T.
Fu, B.
Bassett, P.
Qurashi, I.
ur Rahman, R.
Baig, S.
Kazmi, A.
Corsi-Zuelli, F.
Haddad, P. M.
Deakin, B.
Husain, N.
author_facet Chaudhry, I. B.
Husain, M. O.
Khoso, A. B.
Husain, M. I.
Buch, M. H.
Kiran, T.
Fu, B.
Bassett, P.
Qurashi, I.
ur Rahman, R.
Baig, S.
Kazmi, A.
Corsi-Zuelli, F.
Haddad, P. M.
Deakin, B.
Husain, N.
author_sort Chaudhry, I. B.
collection PubMed
description NMDA autoantibody encephalitis presenting as schizophrenia suggests the possible role of adaptive cell-mediated immunity in idiopathic schizophrenia. However, to our knowledge there have been no trials of the immune-suppressant methotrexate in schizophrenia. We tested if low-dose methotrexate as used in the treatment of systemic autoimmune disorders would be tolerable and effective in people with schizophrenia in a feasibility study. Ninety-two participants within 5 years of schizophrenia diagnosis were recruited from inpatient and outpatient facilities in Karachi, Pakistan. They were randomised to receive once weekly 10-mg oral methotrexate (n = 45) or matching placebo (n = 47) both with daily 5-mg folic acid, in addition to treatment as usual for 12 weeks. There were eight dropouts per group. Side effects were non-significantly more common in those on methotrexate and were not severe. One person developed leukopenia. Positive symptom scores improved more in those receiving methotrexate than placebo (β = −2.5; [95% CI −4.7 to −0.4]), whereas negative symptoms were unaffected by treatment (β = −0.39; [95% CI −2.01 to 1.23]). There were no immune biomarkers but methotrexate did not affect group mean leucocyte counts or C-reactive protein. We conclude that further studies are feasible but should be focussed on subgroups identified by advances in neuroimmune profiling. Methotrexate is thought to work in autoimmune disorders by resetting systemic regulatory T-cell control of immune signalling; we show that a similar action in the CNS would account for otherwise puzzling features of the immuno-pathogenesis of schizophrenia.
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spelling pubmed-77057022020-12-03 A randomised clinical trial of methotrexate points to possible efficacy and adaptive immune dysfunction in psychosis Chaudhry, I. B. Husain, M. O. Khoso, A. B. Husain, M. I. Buch, M. H. Kiran, T. Fu, B. Bassett, P. Qurashi, I. ur Rahman, R. Baig, S. Kazmi, A. Corsi-Zuelli, F. Haddad, P. M. Deakin, B. Husain, N. Transl Psychiatry Article NMDA autoantibody encephalitis presenting as schizophrenia suggests the possible role of adaptive cell-mediated immunity in idiopathic schizophrenia. However, to our knowledge there have been no trials of the immune-suppressant methotrexate in schizophrenia. We tested if low-dose methotrexate as used in the treatment of systemic autoimmune disorders would be tolerable and effective in people with schizophrenia in a feasibility study. Ninety-two participants within 5 years of schizophrenia diagnosis were recruited from inpatient and outpatient facilities in Karachi, Pakistan. They were randomised to receive once weekly 10-mg oral methotrexate (n = 45) or matching placebo (n = 47) both with daily 5-mg folic acid, in addition to treatment as usual for 12 weeks. There were eight dropouts per group. Side effects were non-significantly more common in those on methotrexate and were not severe. One person developed leukopenia. Positive symptom scores improved more in those receiving methotrexate than placebo (β = −2.5; [95% CI −4.7 to −0.4]), whereas negative symptoms were unaffected by treatment (β = −0.39; [95% CI −2.01 to 1.23]). There were no immune biomarkers but methotrexate did not affect group mean leucocyte counts or C-reactive protein. We conclude that further studies are feasible but should be focussed on subgroups identified by advances in neuroimmune profiling. Methotrexate is thought to work in autoimmune disorders by resetting systemic regulatory T-cell control of immune signalling; we show that a similar action in the CNS would account for otherwise puzzling features of the immuno-pathogenesis of schizophrenia. Nature Publishing Group UK 2020-11-30 /pmc/articles/PMC7705702/ /pubmed/33257661 http://dx.doi.org/10.1038/s41398-020-01095-8 Text en © The Author(s) 2020 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Chaudhry, I. B.
Husain, M. O.
Khoso, A. B.
Husain, M. I.
Buch, M. H.
Kiran, T.
Fu, B.
Bassett, P.
Qurashi, I.
ur Rahman, R.
Baig, S.
Kazmi, A.
Corsi-Zuelli, F.
Haddad, P. M.
Deakin, B.
Husain, N.
A randomised clinical trial of methotrexate points to possible efficacy and adaptive immune dysfunction in psychosis
title A randomised clinical trial of methotrexate points to possible efficacy and adaptive immune dysfunction in psychosis
title_full A randomised clinical trial of methotrexate points to possible efficacy and adaptive immune dysfunction in psychosis
title_fullStr A randomised clinical trial of methotrexate points to possible efficacy and adaptive immune dysfunction in psychosis
title_full_unstemmed A randomised clinical trial of methotrexate points to possible efficacy and adaptive immune dysfunction in psychosis
title_short A randomised clinical trial of methotrexate points to possible efficacy and adaptive immune dysfunction in psychosis
title_sort randomised clinical trial of methotrexate points to possible efficacy and adaptive immune dysfunction in psychosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705702/
https://www.ncbi.nlm.nih.gov/pubmed/33257661
http://dx.doi.org/10.1038/s41398-020-01095-8
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