Biomarker Profiles in Psychosis Risk Groups Within Unaffected Relatives Based on Familiality and Age.

Area of Science:

• Neuroscience
• Psychiatry
• Genetics

Background:

• Unaffected relatives (UR) of individuals with psychotic disorders are a valuable group for studying psychosis neurobiology.
• Heterogeneity exists among UR, necessitating stratification by psychosis vulnerability risk factors.

Purpose of the Study:

• To examine cognitive and neurophysiologic biomarkers in first-degree UR of psychosis probands.
• To stratify UR by familiality status and age to identify differentiating biomarkers.
• To explore the relationship between biomarkers and Polygenic Risk Scores for Schizophrenia (PRSSCZ).

Main Methods:

• Utilized the Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) dataset.
• Stratified UR based on proband familiality and UR age (≤30 vs. >30 years).
• Assessed biomarkers including Brief Assessment of Cognition in Schizophrenia (BACS), antisaccade error (ASE) factor, and stop-signal task (SST) factor.

Main Results:

• BACS, ASE, and SST factors differentiated UR from healthy controls (HC).
• No significant differences in biomarker profiles between UR of familial and non-familial probands.
• ASE and SST factors differentiated younger UR from older UR and both age groups from HC.
• BACS and ASE factor associated with PRSSCZ.

Conclusions:

• Cognitive biomarkers, especially impairments in "top-down inhibition" (assessed by ASE and SST), are critical indicators of psychosis vulnerability.
• Age is a significant factor in differentiating UR biomarker profiles.
• These findings advance the understanding of psychosis neurobiology and risk identification.