Biomarker discovery in ultra high risk for psychosis: Towards prediction of psychotic disorder, non-psychotic mental disorders and recovery

Mental disorders such as schizophrenia and major depression are among the most expensive disorders in terms of quality of life and societal cost. Early identification and intervention is associated with improved outcome and is facilitated by targeting those at ultra-high-risk-for-psychosis (UHR) as up to 25-30% subsequently develop psychotic disorder and 50-60% develop depressive disorder. We now seek discriminative plasma protein biomarkers so that these different outcomes can be predicted and different and more effective treatments applied.

There is growing evidence for an inflammatory component to these disorders. We have added to this literature by demonstrating that the complement pathway is dysregulated in blood samples of individuals already at the age 11, many years before these individuals develop psychotic disorder at age 18. Therefore in addition to studying plasma proteins generally we will focus on the complement pathway specifically as a target for early therapeutic and preventative strategies in these disorders.

Our study:

In UHR baseline samples we now propose to establish the exact relationship between levels of these plasma proteins and outcomes of:

1).All UHR subjects vs healthy controls

2). UHR subjects who subsequently develop a psychotic disorder vs those who do not

3).UHR subjects who demonstrate persistence of the UHR / Attenuated Psychotic experiences (APEs) at follow up vs those who do not

4).UHR who transition to mental disorders in a broader sense, i.e. also including major depression and anxiety disorders

5).UHR who make a full recovery (no presenting symptoms and good overall function) vs those who do not.

This will inform us if measures of protein expression in the plasma at first presentation at UHR for psychosis will contribute to predictive models for these disorders.

Our study will be based on two large internationally collected cohort of subjects; one used for discovery, one for validation.


Award Date
29 June 2017
Award Value
Principal Investigator
Professor David Cotter
Host Institution
Royal College of Surgeons in Ireland
Investigator Led Projects