# PEPAMARKER: a multicenter cohort study protocol on predictive biomarkers of affective vs. non-affective trajectories in first-episode psychosis

## TL;DR

This study aims to identify biomarkers that can predict whether a first episode of psychosis will follow an affective or non-affective trajectory, using linguistic and inflammatory markers.

## Contribution

The study introduces a predictive model based on prosodic markers to differentiate psychosis trajectories early in the illness course.

## Key findings

- Prosodic markers from clinical interviews will be used to predict affective vs. non-affective psychosis trajectories.
- Inflammatory biomarkers and linguistic features will be analyzed alongside prosodic markers for predictive accuracy.
- The study will assess the effectiveness of these tools in improving early diagnosis and treatment adaptation.

## Abstract

Psychosis is a severe and disabling mental disorder with peak incidence in late adolescence and early adulthood. Following a first-episode psychosis (FEP), clinical trajectories diverge into affective psychoses or non-affective psychoses. At illness onset, differentiation between these trajectories is frequently impossible, which results in delayed treatment adaptation and increased relapse risk. Predictive biomarkers, particularly linguistic and inflammatory markers, may help refine early diagnosis and personalize care.

The primary objective of the PEPAMARKER study is to develop a predictive model based on prosodic markers to identify affective vs. non-affective trajectories at 2-year follow-up of patients with first-episode psychosis.

PEPAMARKER is a prospective, multicenter, minimal-risk study conducted in five psychiatric centers in France. A total of 217 participants aged 15–30 years with FEP will be enrolled and followed for 24 months. At baseline, data will be collected through clinical interviews (audio-recorded and transcribed), standardized rating scales, and inflammatory markers. Prosodic markers will constitute the primary predictors. Secondary predictors include syntactic/semantic features, inflammatory biomarkers, and clinical rating scales. The primary endpoint is affective vs. non-affective evolution of psychosis at 2 years. Statistical analyses and logistic regression models will be conducted along with the assessment of internal validity.

The study aims to provide accessible predictive tools using clinical interview recordings and basic blood tests to improve early differentiation of psychosis trajectories, which is crucial to a timely treatment adaptation and a reduction in relapse risk.

https://clinicaltrials.gov/, identifier NCT05384392.