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Updated: Jul 5, 2025

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Soluble terminal complement complex blood levels are elevated in schizophrenia.

Susa Savukoski1, Marco Mannes1, Lisa Wohlgemuth1

  • 1Institute of Clinical and Experimental Trauma Immunology, University Hospital Ulm, University of Ulm, Ulm, Germany.

European Archives of Psychiatry and Clinical Neuroscience
|January 19, 2024
PubMed
Summary
This summary is machine-generated.

Schizophrenia patients show higher levels of the terminal complement complex (sTCC), indicating chronic immune activation. This complement marker, sTCC, may serve as a trait marker in schizophrenia, distinct from acute symptoms or treatment effects.

Keywords:
C4C5aClassical pathwayComplement systemConfoundersFirst-episode psychosissTCC

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Area of Science:

  • Neuroimmunology
  • Complement System Biology
  • Psychiatric Research

Background:

  • The role of the complement system in schizophrenia (Sz) remains unclear due to disease heterogeneity and varied study designs.
  • Previous research has yielded inconclusive findings regarding complement activation in Sz patients.

Purpose of the Study:

  • To investigate complement activation products and classical pathway functionality in acutely ill, unmedicated Sz patients compared to controls.
  • To assess changes after 6 weeks of treatment and explore associations with clinical symptoms and inflammatory markers.

Main Methods:

  • Enzyme-linked immunosorbent assay (ELISA) was used to measure terminal complement complex (sTCC) and C5a in plasma from 96 Sz patients and 96 controls.
  • Sub-group analyses included C4 component and classical pathway activity in serum.
  • Aligned Rank Transformation (ART) models were employed to account for covariates like age and sex.

Main Results:

  • No significant differences were found in C5a, C4, or classical pathway function between Sz patients and controls.
  • Plasma sTCC levels were significantly elevated in Sz patients compared to controls (p=0.027).
  • Elevated sTCC was associated with C-reactive protein (CRP; p=0.006) but not with clinical symptom severity or treatment response.

Conclusions:

  • Elevated sTCC in schizophrenia patients suggests a role in chronic, non-specific immune activation, similar to CRP.
  • sTCC may function as a trait marker for schizophrenia, reflecting underlying immune dysregulation.
  • Longitudinal studies are recommended to understand the temporal dynamics of innate immune changes in psychosis development.