Background and hypothesis: Recent evidence has highlighted the benefits of early detection and treatment for

better clinical outcomes in patients with psychosis. Biological markers of the disease have become a focal point of

research. This study aimed to identify protein markers detectable in the early stages of psychosis and indicators

of progression by comparing them with those of healthy controls (HC) and first episode psychosis (FEP).

Study design: The participants comprised 28 patients in the clinical high-risk (CHR) group, 49 patients with FEP,

and 61 HCs aged 15–35 years. Blood samples were collected and analyzed using multiple reaction monitoringmass

spectrometry to measure the expression of 158 peptide targets. Data were adjusted for age, sex, and use of

psychotropic drugs.

Study results: A total of 18 peptides (17 proteins) differed significantly among the groups. The protein PRDX2 was

higher in the FEP group than in the CHR and HC groups and showed increased expression according to disease

progression. The levels of six proteins were significantly higher in the FEP group than in the CHR group. Nine

proteins differed significantly in the CHR group compared to the other groups. Sixteen proteins were significantly

correlated with symptom severity. These proteins are primarily related to the coagulation cascade, inflammatory

response, brain structure, and synaptic plasticity.

Conclusions: Our findings suggested that peripheral protein markers reflect disease progression in patients with

psychosis. Further longitudinal research is needed to confirm these findings and to identify the specific roles of

these markers in the pathogenesis of schizophrenia.