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Minor immunomodulatory effects of psychotropics suggested in severe mental disorders: Associations of antipsychotics with beta defensin 2, antidepressants with C-reactive protein, and mood stabilizers with soluble interleukin 2 receptor

M. Ormerod,Mashhood Ahmed Sheikh,T. Ueland,G. Hjell,L. Rødevand,L. Sæther,S. H. Lunding,I. Johansen,D. Andreou,T. Ueland,T. Lagerberg,I. Melle,S. Djurovic,O. Andreassen,N. E. Steen

Published 2025 in European psychiatry

ABSTRACT

Abstract Background Immunomodulatory effects of psychotropic agents used to treat severe mental disorders (SMDs) have been suggested. We investigated associations between immune marker levels and antipsychotic- (AP), antidepressant- (AD), and mood stabilizing agents (MS) use in SMDs. Methods We included 1215 participants with SMDs (777 with schizophrenia spectrum disorders and 438 with bipolar disorders). Circulating levels of 45 immune markers were determined by enzyme-immunoassay or immunoturbidimetry and analyzed for associations with use, doses, and serum concentrations of AP, AD, and MS. Extensive adjustments for potential confounders were performed. Immune marker levels of 1008 healthy controls served as a reference. Results AP use was significantly associated with higher plasma levels of beta defensin 2 (BD-2) (β = 0.094, p = 0.8E-4), AD use with higher serum levels of CRP (β = 0.072, p = 0.8E-3), and MS use with higher plasma levels of soluble interleukin 2 receptor (sIL-2R) (β = 0.063, p = 0.9E-4). These findings were paralleled by positive associations with psychotropic agent dose and serum concentrations: AP dose was associated with BD-2 levels (β = 0.045, p = 2.3E-4), AD dose with CRP levels (β = 0.039, p = 0.001), MS dose with sIL-2R levels (β = 0.048, p = 0.001), and serum concentration of AD was nominally positively associated with CRP (β = 0.072, p = 0.002). Conclusions The findings suggest that AP and MS use affect pathways involved in immune homeostasis and inflammatory regulation in individuals with SMDs, while AD use augments low-grade systemic inflammation reflected by CRP.

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