The identification of plasma protein markers of antipsychotic drug treatment response in first episode psychosis; a proteomic analysis of baseline plasma samples from the OPTiMiSE and PSYSCAN studies.

Schizophrenia is amongst the most expensive disorders in terms of quality of life and societal cost. While early intervention is known to be associated with improved outcome there is little information on predictors of patient outcome following antipsychotic drug (APD) treatment. We seek to identify, for the first time, discriminative plasma protein biomarkers of patient outcomes following standard first line antipsychotic treatment.

We and others have implicated the complement pathway and other plasma proteins in psychosis (see preliminary data). The complement pathway generally is upregulated in individuals:

  1. at age 11, before the development of psychotic disorder or psychotic experiences at age 18.
  2. who transition to psychotic disorder from the at risk mental state (ARMS)

And we now have preliminary data indicating that the complement pathway maybe upregulated in the first episode of psychosis (FEP) in subjects who have a poor outcome following antipsychotic treatment (see preliminary data).

Based on these findings we hypothesise that upregulation of the complement pathway is associated with poor outcome following APD treatment. We will test this hypothesis. We will also test other implicated pathways and proteins

Our proposed study:

In first episode psychosis (FEP) baseline plasma samples we now propose to establish the relationship between the levels of these complement plasma proteins (and other candidate proteins) to clinical outcome and function following antipsychotic drug (APD) treatment.

We will undertake this study in one large and respected international sample and replicate it in another similar sample.

The primary outcome of this study is to identify plasma protein markers of antipsychotic drug treatment response at first presentation with psychotic illness.

As a secondary outcome, our data will be analysed in combination with other functional outcome data and neuroimaging and genomic data to identify the most predictive model of outcome following antipsychotic drug treatment in FEP.

Award Date
27 June 2019
Award Value
Principal Investigator
Professor David Cotter
Host Institution
Royal College of Surgeons in Ireland
Investigator Led Projects