Inflammation and cognition in severe mental illness: patterns of covariation and subgroups

A potential relationship between dysregulation of immune/inflammatory pathways and cognitive impairment has been suggested in severe mental illnesses (SMI), such as schizophrenia (SZ) and bipolar (BD) spectrum disorders. However, multivariate relationships between peripheral inflammatory/immune-rela...

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Published in:Molecular psychiatry 2023-03, Vol.28 (3), p.1284-1292
Main Authors: Sæther, Linn Sofie, Ueland, Thor, Haatveit, Beathe, Maglanoc, Luigi Angelo, Szabo, Attila, Djurovic, Srdjan, Aukrust, Pål, Roelfs, Daniel, Mohn, Christine, Ormerod, Monica Bettina Elkjaer Greenwood, Lagerberg, Trine Vik, Steen, Nils Eiel, Melle, Ingrid, Andreassen, Ole Andreas, Ueland, Torill
Format: Article
Language:English
Subjects:
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Antipsychotics
Behavioral Sciences
Biological Psychology
Biomarkers
Bipolar Disorder - diagnosis
Cognition
Cognition & reasoning
Cognitive ability
Correlation analysis
Humans
Immune status
Inflammation
Inflammation - complications
Information processing
Innate immunity
Interleukin 18
Medicine
Medicine & Public Health
Mental disorders
Neuropsychological Tests
Neurosciences
Pharmacotherapy
Psychiatry
Schizophrenia
Schizophrenia - complications
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Summary:A potential relationship between dysregulation of immune/inflammatory pathways and cognitive impairment has been suggested in severe mental illnesses (SMI), such as schizophrenia (SZ) and bipolar (BD) spectrum disorders. However, multivariate relationships between peripheral inflammatory/immune-related markers and cognitive domains are unclear, and many studies do not account for inter-individual variance in both cognitive functioning and inflammatory/immune status. This study aimed to investigate covariance patterns between inflammatory/immune-related markers and cognitive domains and further elucidate heterogeneity in a large SMI and healthy control (HC) cohort (SZ = 343, BD = 289, HC = 770). We applied canonical correlation analysis (CCA) to identify modes of maximum covariation between a comprehensive selection of cognitive domains and inflammatory/immune markers. We found that poor verbal learning and psychomotor processing speed was associated with higher levels of interleukin-18 system cytokines and beta defensin 2, reflecting enhanced activation of innate immunity, a pattern augmented in SMI compared to HC. Applying hierarchical clustering on covariance patterns identified by the CCA revealed a high cognition—low immune dysregulation subgroup with predominantly HC (24% SZ, 45% BD, 74% HC) and a low cognition—high immune dysregulation subgroup predominantly consisting of SMI patients (76% SZ, 55% BD, 26% HC). These subgroups differed in IQ, years of education, age, CRP, BMI (all groups), level of functioning, symptoms and defined daily dose (DDD) of antipsychotics (SMI cohort). Our findings suggest a link between cognitive impairment and innate immune dysregulation in a subset of individuals with severe mental illness.
ISSN:1359-4184
1476-5578
1476-5578
DOI:10.1038/s41380-022-01924-w