‘Investigating the relationship between the Complement Pathway and outcomes in Psychosis; from Clinical High Risk to First Episode Psychosis’

Schizophrenia is amongst the most expensive disorders in terms of quality of life and societal cost. Based on current treatments more than 30% of schizophrenia subjects do not respond to treatments, including antipsychotic medications. While early intervention is known to be associated with improved outcome, we cannot tell in advance which patients with a first or recent psychotic onset psychotic illness will do well or not.

Our own recent research has identified that a set of blood proteins, belonging to the complement and coagulation pathways, are altered in early psychosis. These proteins are involved in the process of fighting infection and clotting in the body, but their importance in psychosis lies in their equally important roles in modulating inflammation in the body and in the regular turn-over of synapses or junctions between brain cells. We have found that these complement and coagulation proteins are altered in the blood of young people;

  • at age 11 - before they develop psychotic experiences
  • who transition from being clinical high-risk (CHR) to having a psychotic disorder (PD)
  • who have a good outcome following their first episode of psychosis (FEP)
  • These findings are novel. They may help inform treatment choices in the future. However significant questions remain and we need to;


  • Find out if observing patterns of change in these proteins over time in young people at risk of psychotic disorder will give better information on likely outcomes.


  • Confirm that levels of these proteins at first presentation are predictive of better future outcomes in a larger group with FEP, and in “real world” conditions.
  • Check that the effect is seen with treatments other than amisulpiride.

Our proposed study:

We will use well established methods and blood samples donated from unique, large, internationally study cohorts to study these questions.

Award Date
01 July 2022
Award Value
Principal Investigator
Professor David Cotter
Host Institution
Royal College of Surgeons in Ireland
Investigator Led Projects