Association of Complement and Coagulation Pathway Proteins with Treatment Response in First-Episode Psychosis: A Longitudinal Analysis of the Optimise Clinical Trial

Background

Treatment responses to specific antipsychotic drugs are tricky to predict on clinical grounds alone.  The current analysis hypothesizes that the baseline complement pathway activity predicts the treatment response and analyzes the relationship between baseline plasma biomarkers with treatment response to antipsychotic drugs.

Methods

• Baseline plasma samples were collected from a multi-center clinical trial from the first episode of psychosis patients (n= 243). 
• The participants were treated with amisulpride for 4 weeks.
• Coagulation proteins and complement levels at baseline were estimated using both data-dependent and data-independent mass spectrometry approaches. 
• The primary outcome was remission status at 4 weeks and the secondary outcomes included changes in psychotic and functional symptoms throughout treatment.   
• In addition, immunoassays were conducted at baseline for complement component (C₁R), as well as for activation markers complement component (C₄a) and soluble membrane attack complex (sC₅b-₉).

Results

• The plasma level of the complement variant C4a was significantly associated with remission at 4 weeks. 
• Moreover, higher levels of several complement and coagulation pathways were associated with a decrease in psychotic symptoms and progress in functioning. 
• Immunoassays indicated an association of levels of C₁R and C₄a as well as complement activation markers sC₅b-₉ levels with treatment response.

Conclusion

The results indicated that the response to antipsychotic therapy might be related to pre-treatment levels of plasma complement and coagulation pathway proteins. This is constant with independent evidence associating immune dysfunction with the pathophysiology of psychosis. Moreover, these outcomes inform the development of novel therapeutic methods that target the complement system for psychosis.