Risk of Schizophrenia and Bipolar Disorder in Patients With Multiple Sclerosis: Record-Linkage Studies

Meier, Ute‐Christiane; Ramagopalan, Sreeram; Goldacre, Michael J; Goldacre, Raph

doi:10.3389/fpsyt.2020.00662

Cited by 14 publications

(6 citation statements)

References 17 publications

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“…Similar to MS, schizophrenia is often considered to be associated with the dysregulation of the immune response and chronic inflammation in the CNS (Pape et al, 2019). In contrast, schizophrenia‐like symptoms have also been described in some patients with MS (Meier et al, 2020). This suggests that the dysregulated immune system and inflammation observed in schizophrenia and MS could overlap to some extent.…”

Section: Discussionmentioning

confidence: 99%

Fingolimod ameliorates schizophrenia‐like cognitive impairments induced by phencyclidine in male rats

Long

et al. 2022

British J Pharmacology

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Background and Purpose Improvement of cognitive deficits in schizophrenia remains an unmet need owing to the lack of new therapies and drugs. Recent studies have reported that fingolimod, an immunomodulatory drug for treating multiple sclerosis, demonstrates anti‐inflammatory and neuroprotective effects in several neurological disease models. This suggests its usefulness for ameliorating cognitive dysfunction in schizophrenia. Herein, we assessed the efficacy profile and mechanism of fingolimod in a rat model of phencyclidine (PCP)‐induced schizophrenia. Experimental Approach Male Sprague–Dawley rats were treated with PCP for 14 days. The therapeutic effect of fingolimod on cognitive function was assessed using the Morris water maze and fear conditioning tests. Hippocampal neurogenesis and the expression of astrocytes and microglia were evaluated using immunostaining. Cytokine expression was quantified using multiplexed flow cytometry. Brain‐derived neurotrophic factor expression and phosphorylation of extracellular signal‐regulated kinase were determined using western blot analysis. Key Results Fingolimod attenuated cognitive deficits and restored hippocampal neurogenesis in a dose‐dependent manner in PCP‐treated rats. Fingolimod treatment exerted anti‐inflammatory effects by inhibiting microglial activation and IL‐6 and IL‐1β pro‐inflammatory cytokine expression. The underlying mechanism involves the upregulation of brain‐derived neurotrophic factor protein expression and activation of the ERK signalling pathway. Conclusion and Implications This is the first preclinical assessment of the effects of fingolimod on cognitive function in a model for schizophrenia. Our results suggest the immune system plays an crucial role in cognitive alterations in schizophrenia and highlight the potential of immunomodulatory strategies to improve cognitive deficits in schizophrenia.

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Section: Discussionmentioning

confidence: 99%

Fingolimod ameliorates schizophrenia‐like cognitive impairments induced by phencyclidine in male rats

Long

et al. 2022

British J Pharmacology

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“…Four studies expressed concerns about the coding systems 21 26–28. One study pointed out recording differences between versions 9 and 10 of the International Statistical Classification of Diseases and Related Health Problems (ICD) 27…”

Section: Resultsmentioning

confidence: 99%

Evaluation of the reported data linkage process and associated quality issues for linked routinely collected healthcare data in multimorbidity research: a systematic methodology review

et al. 2023

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ObjectiveThe objective of this systematic review was to examine how the record linkage process is reported in multimorbidity research.MethodsA systematic search was conducted in Medline, Web of Science and Embase using predefined search terms, and inclusion and exclusion criteria. Published studies from 2010 to 2020 using linked routinely collected data for multimorbidity research were included. Information was extracted on how the linkage process was reported, which conditions were studied together, which data sources were used, as well as challenges encountered during the linkage process or with the linked dataset.ResultsTwenty studies were included. Fourteen studies received the linked dataset from a trusted third party. Eight studies reported variables used for the data linkage, while only two studies reported conducting prelinkage checks. The quality of the linkage was only reported by three studies, where two reported linkage rate and one raw linkage figures. Only one study checked for bias by comparing patient characteristics of linked and non-linked records.ConclusionsThe linkage process was poorly reported in multimorbidity research, even though this might introduce bias and potentially lead to inaccurate inferences drawn from the results. There is therefore a need for increased awareness of linkage bias and transparency of the linkage processes, which could be achieved through better adherence to reporting guidelines.PROSPERO registration numberCRD42021243188.

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“…Similar to MS, schizophrenia is often considered to be associated with the dysregulation of the immune response and chronic inflammation in the CNS (Pape, Tamouza et al, 2019). In contrast, schizophrenia-like symptoms have also been described in some patients with MS (Meier, Ramagopalan et al, 2020). This suggests that the dysregulated immune system and inflammation observed in schizophrenia and MS somewhat overlap.…”

Section: Discussionmentioning

confidence: 99%

Fingolimod ameliorates cognitive impairments in a phencyclidine-induced rat model of schizophrenia

et al. 2022

Preprint

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Background and Purpose: Improvement of cognitive deficits in schizophrenia remains an unmet need due to the lack of new therapies and drugs. Recent studies have reported that fingolimod, an immunomodulatory drug for treating multiple sclerosis, demonstrates anti-inflammatory and neuroprotective effects in several neurological disease models. This suggests its usefulness for ameliorating cognitive dysfunction in schizophrenia. Herein, we assessed the efficacy profile and mechanism of fingolimod in a rat model of phencyclidine (PCP)-induced schizophrenia. Experimental Approach: Sprague-Dawley rats were treated with PCP for 14 days. The therapeutic effect of fingolimod on cognitive function was assessed using the Morris water maze and fear conditioning tests. Hippocampal neurogenesis and the expression of astrocytes and microglia were evaluated by immunostaining. Cytokine expression was quantified using multiplexed flow cytometry. Brain-derived neurotrophic factor expression and phosphorylation of extracellular signal-regulated kinase were determined using western blot analysis. Key Results: Fingolimod attenuated cognitive deficits and restored hippocampal neurogenesis in a dose-dependent manner in PCP-treated rats. Fingolimod treatment exerted anti-inflammatory effects by inhibiting microglial activation and IL-6 and IL-1β pro-inflammatory cytokine expression. The underlying mechanism involves the upregulation of brain-derived neurotrophic factor protein expression and activation of the extracellular signal-regulated kinase signalling pathway. Conclusion and Implications: To the best of our knowledge, this is the first preclinical study to assess the effects of fingolimod on cognitive function in schizophrenia models. Our results support the role of the immune system in cognitive alterations in schizophrenia and highlight the potential of immunomodulatory strategies to improve cognitive deficits in schizophrenia.

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Risk of Schizophrenia and Bipolar Disorder in Patients With Multiple Sclerosis: Record-Linkage Studies

Cited by 14 publications

References 17 publications

Fingolimod ameliorates schizophrenia‐like cognitive impairments induced by phencyclidine in male rats

Fingolimod ameliorates schizophrenia‐like cognitive impairments induced by phencyclidine in male rats

Evaluation of the reported data linkage process and associated quality issues for linked routinely collected healthcare data in multimorbidity research: a systematic methodology review

Fingolimod ameliorates cognitive impairments in a phencyclidine-induced rat model of schizophrenia

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