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Complement pathway changes at age 12 are associated with psychotic experiences at age 18 in a longitudinal

Melanie Föcking1, Sophie Sabherwal2, Hannah M Cates3

  • 1Department of Psychiatry, Royal College of Surgeons in Ireland, Dublin, Ireland. mfocking@rcsi.ie.

Molecular Psychiatry
|January 13, 2019
PubMed

Insights

The study found that specific complement proteins were elevated in individuals who later experienced psychotic experiences. These findings suggest a link between complement pathway dysregulation and stress-related psychiatric disorders.

Area of Science:

  • Immunology
  • Neuroscience
  • Psychiatry

Background:

  • The complement cascade is crucial for immune defense.
  • Dysregulated complement pathways are increasingly implicated in psychiatric disorders.

Purpose of the Study:

  • To investigate the role of complement signaling proteins in the development of psychotic experiences.
  • To explore the association between complement protein levels and psychiatric outcomes.

Main Methods:

  • Directed proteomic analysis of 29 complement pathway proteins using data-independent acquisition.
  • Comparison of protein expression in adolescents with and without psychotic experiences from the UK Avon Longitudinal Study of Parents and Children (ALSPAC) cohort.
  • Unbiased plasma proteomic analysis in mice exposed to chronic social stress.

Main Results:

  • Six complement proteins (VTN, C1RL, C8B, C8A, CFH, C5) were significantly upregulated in individuals with psychotic experiences.
  • Eleven complement proteins were dysregulated in mice under chronic social stress.
  • Three proteins (C1R, CFH, C5) showed similar dysregulation patterns in both humans and stressed mice.

Conclusions:

  • Blood-based complement protein dysregulation is associated with the incidence of psychotic experiences.
  • These complement changes may be linked to exposure to stress.
  • The complement system represents a potential biomarker and therapeutic target for stress-related psychiatric conditions.

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