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Serum complement proteins rather than inflammatory factors is effective in predicting psychosis in individuals at

TianHong Zhang1, JiaHui Zeng2, JiaYi Ye2

  • 1Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai Intelligent Psychological Evaluation and Intervention Engineering Technology Research Center (20DZ2253800), Shanghai Key Laboratory of Psychotic Disorders, Shanghai, 200030, PR China. zhang_tianhong@126.com.

Translational Psychiatry
|January 11, 2023
PubMed

Insights

Complement system alterations, not inflammation, better predict psychosis onset in individuals at clinical high risk. Lower levels of complement proteins like C5 and C3 indicate higher risk for developing psychosis.

Area of Science:

  • Neuroimmunology
  • Psychiatry
  • Complement System Biology

Background:

  • Immunological and inflammatory factors are linked to psychosis development.
  • The role of the complement system, a key inflammation driver, in predicting psychosis onset remains unclear.
  • Distinguishing between inflammatory markers and complement factors for predictive performance is crucial.

Purpose of the Study:

  • To compare the alteration and predictive performance of inflammation and complement factors in individuals at clinical high risk (CHR) for psychosis.
  • To identify which factors, inflammatory cytokines or complement proteins, are more effective in predicting the conversion to psychosis.

Main Methods:

  • Enrolled 49 individuals at CHR and 26 healthy controls (HCs).
  • Measured inflammatory cytokines (IL-1β, IL-6, IL-8, IL-10, TNF-α, M-CSF) and complement proteins (C1q, C2, C3, C3b, C4, C4b, C5, C5a, Factor B, D, I, H) at baseline using ELISA.
  • Followed up participants for 3 years to identify CHR individuals who converted to psychosis (n=25).

Main Results:

  • Significantly lower levels of complement proteins C5, C3, D, I, and H were observed in the CHR group compared to HCs.
  • Individuals who converted to psychosis showed significantly lower levels of C5 and C5a compared to non-converters.
  • Complement factors, particularly C5a and C5, demonstrated significant predictive performance for psychosis conversion, unlike most inflammatory markers.

Conclusions:

  • Altered complement levels in the CHR population are more strongly associated with conversion to psychosis than inflammatory factors.
  • An activated complement system may precede the first episode of psychosis and contribute to its neuropathogenesis.
  • Complement system activation could serve as a potential biomarker for psychosis risk prediction in CHR individuals.

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