Changes in immunoglobulin levels during clozapine treatment in schizophrenia

Kira Griffiths; Maria ruiz Mellado; Raymond Chung; John Lally; Grant McQueen; Kyra-Verena Sendt; Amy Gillespie; Muhammad Ibrahim; Alex Richter; Adrian Shields; Mark Ponsford; Stephen Jolles; John Hodsoll; Thomas A. Pollak; Rachel Upthegrove; Alice Egerton; James H. Maccabe

doi:10.1016/j.bbi.2023.10.001

Changes in immunoglobulin levels during clozapine treatment in schizophrenia

Kira Griffiths, Maria ruiz Mellado, Raymond Chung, John Lally, Grant McQueen, Kyra-Verena Sendt, Amy Gillespie, Muhammad Ibrahim, Alex Richter, Adrian Shields, Mark Ponsford, Stephen Jolles, John Hodsoll, Thomas A. Pollak, Rachel Upthegrove, Alice Egerton, James H. Maccabe^*

^*Corresponding author for this work

Psychology

Research output: Contribution to journal › Article › peer-review

Abstract

BACKGROUND AND HYPOTHESIS: Use of clozapine in treatment-resistant schizophrenia is often limited due to risk of adverse effects. Cross-sectional associations between clozapine treatment and low immunoglobulin levels have been reported, however prospective studies are required to establish temporal relationships. We tested the hypothesis that reductions in immunoglobulin levels would occur over the first 6 months following initiation of clozapine treatment. Relationships between immunoglobulin levels and symptom severity over the course of clozapine treatment were also explored.

DESIGN: This prospective observational study measured immunoglobulin (Ig) levels (A, M and G) in 56 patients with treatment-resistant schizophrenia at 6-, 12- and 24-weeks following initiation with clozapine. Clinical symptoms were also measured at 12 weeks using the positive and negative syndrome scale (PANSS).

RESULTS: IgA, IgG and IgM all decreased during clozapine treatment. For IgA and IgG the reduction was significant at 24 weeks (IgA: β = -32.66, 95% CI = -62.38, -2.93, p = 0.03; IgG: β = -63.96, 95% CI = -118.00, -9.31, p = 0.02). For IgM the reduction was significant at 12 and 24 weeks (12 weeks: β = -23.48, 95% CI = -39.56, -7.42, p = 0.004; 24 weeks: β = -33.12, 95 %CI = -50.30, -15.94, p = <0.001). Reductions in IgA and IgG during clozapine treatment were correlated with reductions in PANSS-total over 12 weeks (n = 32, IgA r = 0.59, p = 0.005; IgG r = 0.48, p = 0.03).

CONCLUSIONS: The observed reductions in immunoglobulin levels over six months of clozapine treatment add further evidence linking clozapine to secondary antibody deficiency. Associations between Ig reduction and symptom improvement may however indicate that immune mechanisms contribute to both desirable and undesirable effects of clozapine.

Original language	English
Pages (from-to)	223-228
Number of pages	6
Journal	Brain, Behavior, and Immunity
Volume	115
Early online date	11 Oct 2023
DOIs	https://doi.org/10.1016/j.bbi.2023.10.001
Publication status	Published - Jan 2024

Bibliographical note

Funding:
This work was funded by a grant to JHM from the European Union FP-7 programme, ‘CRESTAR,’ grant reference 13/LO/1857, and a grant to AE from the Medical Research Council, UK, Grant MR/L003988/1. This study presents independent research funded in part by the National Institute for Health Research (NIHR), Biomedical Research Centre at South London and Maudsley National Health Service (NHS) Foundation Trust and King’s College London. This work is also supported by the NIHR Oxford Health Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.

Copyright:
© 2023. Published by Elsevier Inc.

Keywords

Humans
Clozapine/therapeutic use
Schizophrenia/drug therapy
Antipsychotic Agents/adverse effects
Cross-Sectional Studies
Immunoglobulin A
Immunoglobulin G
Immunoglobulin M

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Griffiths, K., Mellado, M. R., Chung, R., Lally, J., McQueen, G., Sendt, K.-V., Gillespie, A., Ibrahim, M., Richter, A., Shields, A., Ponsford, M., Jolles, S., Hodsoll, J., Pollak, T. A., Upthegrove, R., Egerton, A., & Maccabe, J. H. (2024). Changes in immunoglobulin levels during clozapine treatment in schizophrenia. Brain, Behavior, and Immunity, 115, 223-228. https://doi.org/10.1016/j.bbi.2023.10.001

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title = "Changes in immunoglobulin levels during clozapine treatment in schizophrenia",

abstract = "BACKGROUND AND HYPOTHESIS: Use of clozapine in treatment-resistant schizophrenia is often limited due to risk of adverse effects. Cross-sectional associations between clozapine treatment and low immunoglobulin levels have been reported, however prospective studies are required to establish temporal relationships. We tested the hypothesis that reductions in immunoglobulin levels would occur over the first 6 months following initiation of clozapine treatment. Relationships between immunoglobulin levels and symptom severity over the course of clozapine treatment were also explored.DESIGN: This prospective observational study measured immunoglobulin (Ig) levels (A, M and G) in 56 patients with treatment-resistant schizophrenia at 6-, 12- and 24-weeks following initiation with clozapine. Clinical symptoms were also measured at 12 weeks using the positive and negative syndrome scale (PANSS).RESULTS: IgA, IgG and IgM all decreased during clozapine treatment. For IgA and IgG the reduction was significant at 24 weeks (IgA: β = -32.66, 95% CI = -62.38, -2.93, p = 0.03; IgG: β = -63.96, 95% CI = -118.00, -9.31, p = 0.02). For IgM the reduction was significant at 12 and 24 weeks (12 weeks: β = -23.48, 95% CI = -39.56, -7.42, p = 0.004; 24 weeks: β = -33.12, 95 %CI = -50.30, -15.94, p = <0.001). Reductions in IgA and IgG during clozapine treatment were correlated with reductions in PANSS-total over 12 weeks (n = 32, IgA r = 0.59, p = 0.005; IgG r = 0.48, p = 0.03).CONCLUSIONS: The observed reductions in immunoglobulin levels over six months of clozapine treatment add further evidence linking clozapine to secondary antibody deficiency. Associations between Ig reduction and symptom improvement may however indicate that immune mechanisms contribute to both desirable and undesirable effects of clozapine.",

keywords = "Humans, Clozapine/therapeutic use, Schizophrenia/drug therapy, Antipsychotic Agents/adverse effects, Cross-Sectional Studies, Immunoglobulin A, Immunoglobulin G, Immunoglobulin M",

author = "Kira Griffiths and Mellado, {Maria ruiz} and Raymond Chung and John Lally and Grant McQueen and Kyra-Verena Sendt and Amy Gillespie and Muhammad Ibrahim and Alex Richter and Adrian Shields and Mark Ponsford and Stephen Jolles and John Hodsoll and Pollak, {Thomas A.} and Rachel Upthegrove and Alice Egerton and Maccabe, {James H.}",

note = "Funding: This work was funded by a grant to JHM from the European Union FP-7 programme, {\textquoteleft}CRESTAR,{\textquoteright} grant reference 13/LO/1857, and a grant to AE from the Medical Research Council, UK, Grant MR/L003988/1. This study presents independent research funded in part by the National Institute for Health Research (NIHR), Biomedical Research Centre at South London and Maudsley National Health Service (NHS) Foundation Trust and King{\textquoteright}s College London. This work is also supported by the NIHR Oxford Health Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. Copyright: {\textcopyright} 2023. Published by Elsevier Inc.",

year = "2024",

month = jan,

doi = "10.1016/j.bbi.2023.10.001",

language = "English",

volume = "115",

pages = "223--228",

journal = "Brain, Behavior, and Immunity",

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Griffiths, K, Mellado, MR, Chung, R, Lally, J, McQueen, G, Sendt, K-V, Gillespie, A, Ibrahim, M, Richter, A , Shields, A, Ponsford, M, Jolles, S, Hodsoll, J, Pollak, TA, Upthegrove, R, Egerton, A & Maccabe, JH 2024, 'Changes in immunoglobulin levels during clozapine treatment in schizophrenia', Brain, Behavior, and Immunity, vol. 115, pp. 223-228. https://doi.org/10.1016/j.bbi.2023.10.001

TY - JOUR

T1 - Changes in immunoglobulin levels during clozapine treatment in schizophrenia

AU - Griffiths, Kira

AU - Mellado, Maria ruiz

AU - Chung, Raymond

AU - Lally, John

AU - McQueen, Grant

AU - Sendt, Kyra-Verena

AU - Gillespie, Amy

AU - Ibrahim, Muhammad

AU - Richter, Alex

AU - Shields, Adrian

AU - Ponsford, Mark

AU - Jolles, Stephen

AU - Hodsoll, John

AU - Pollak, Thomas A.

AU - Upthegrove, Rachel

AU - Egerton, Alice

AU - Maccabe, James H.

N1 - Funding: This work was funded by a grant to JHM from the European Union FP-7 programme, ‘CRESTAR,’ grant reference 13/LO/1857, and a grant to AE from the Medical Research Council, UK, Grant MR/L003988/1. This study presents independent research funded in part by the National Institute for Health Research (NIHR), Biomedical Research Centre at South London and Maudsley National Health Service (NHS) Foundation Trust and King’s College London. This work is also supported by the NIHR Oxford Health Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. Copyright: © 2023. Published by Elsevier Inc.

PY - 2024/1

Y1 - 2024/1

N2 - BACKGROUND AND HYPOTHESIS: Use of clozapine in treatment-resistant schizophrenia is often limited due to risk of adverse effects. Cross-sectional associations between clozapine treatment and low immunoglobulin levels have been reported, however prospective studies are required to establish temporal relationships. We tested the hypothesis that reductions in immunoglobulin levels would occur over the first 6 months following initiation of clozapine treatment. Relationships between immunoglobulin levels and symptom severity over the course of clozapine treatment were also explored.DESIGN: This prospective observational study measured immunoglobulin (Ig) levels (A, M and G) in 56 patients with treatment-resistant schizophrenia at 6-, 12- and 24-weeks following initiation with clozapine. Clinical symptoms were also measured at 12 weeks using the positive and negative syndrome scale (PANSS).RESULTS: IgA, IgG and IgM all decreased during clozapine treatment. For IgA and IgG the reduction was significant at 24 weeks (IgA: β = -32.66, 95% CI = -62.38, -2.93, p = 0.03; IgG: β = -63.96, 95% CI = -118.00, -9.31, p = 0.02). For IgM the reduction was significant at 12 and 24 weeks (12 weeks: β = -23.48, 95% CI = -39.56, -7.42, p = 0.004; 24 weeks: β = -33.12, 95 %CI = -50.30, -15.94, p = <0.001). Reductions in IgA and IgG during clozapine treatment were correlated with reductions in PANSS-total over 12 weeks (n = 32, IgA r = 0.59, p = 0.005; IgG r = 0.48, p = 0.03).CONCLUSIONS: The observed reductions in immunoglobulin levels over six months of clozapine treatment add further evidence linking clozapine to secondary antibody deficiency. Associations between Ig reduction and symptom improvement may however indicate that immune mechanisms contribute to both desirable and undesirable effects of clozapine.

AB - BACKGROUND AND HYPOTHESIS: Use of clozapine in treatment-resistant schizophrenia is often limited due to risk of adverse effects. Cross-sectional associations between clozapine treatment and low immunoglobulin levels have been reported, however prospective studies are required to establish temporal relationships. We tested the hypothesis that reductions in immunoglobulin levels would occur over the first 6 months following initiation of clozapine treatment. Relationships between immunoglobulin levels and symptom severity over the course of clozapine treatment were also explored.DESIGN: This prospective observational study measured immunoglobulin (Ig) levels (A, M and G) in 56 patients with treatment-resistant schizophrenia at 6-, 12- and 24-weeks following initiation with clozapine. Clinical symptoms were also measured at 12 weeks using the positive and negative syndrome scale (PANSS).RESULTS: IgA, IgG and IgM all decreased during clozapine treatment. For IgA and IgG the reduction was significant at 24 weeks (IgA: β = -32.66, 95% CI = -62.38, -2.93, p = 0.03; IgG: β = -63.96, 95% CI = -118.00, -9.31, p = 0.02). For IgM the reduction was significant at 12 and 24 weeks (12 weeks: β = -23.48, 95% CI = -39.56, -7.42, p = 0.004; 24 weeks: β = -33.12, 95 %CI = -50.30, -15.94, p = <0.001). Reductions in IgA and IgG during clozapine treatment were correlated with reductions in PANSS-total over 12 weeks (n = 32, IgA r = 0.59, p = 0.005; IgG r = 0.48, p = 0.03).CONCLUSIONS: The observed reductions in immunoglobulin levels over six months of clozapine treatment add further evidence linking clozapine to secondary antibody deficiency. Associations between Ig reduction and symptom improvement may however indicate that immune mechanisms contribute to both desirable and undesirable effects of clozapine.

KW - Humans

KW - Clozapine/therapeutic use

KW - Schizophrenia/drug therapy

KW - Antipsychotic Agents/adverse effects

KW - Cross-Sectional Studies

KW - Immunoglobulin A

KW - Immunoglobulin G

KW - Immunoglobulin M

U2 - 10.1016/j.bbi.2023.10.001

DO - 10.1016/j.bbi.2023.10.001

M3 - Article

C2 - 37832895

SN - 0889-1591

VL - 115

SP - 223

EP - 228

JO - Brain, Behavior, and Immunity

JF - Brain, Behavior, and Immunity

ER -

Changes in immunoglobulin levels during clozapine treatment in schizophrenia

Abstract

Bibliographical note

Keywords

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Cite this