Multimodal prediction of psychotic-like experiences using elastic net modeling: external validation in a clinical...

Psychotic-like experiences (PLEs) are considered a subclinical component of psychosis continuum. Studies indicate that PLEs arise from multimodal factors, yet research comprehensively examining these factors together remains scarce. Using a large youth sample, we present the first model that simultaneously examines multimodal factors related to PLEs. As a secondary aim, we evaluate the model's ability to explain psychosis in an external validation cohort that included individuals experiencing psychosis.

After applying variable selection including generalized estimating equations, correlation filtering, Least Absolute Shrinkage and Selection Operator model to 741 variables (i.e., environmental factors, cognitive appraisals, clinical variables, cognitive functioning, and structural brain connectome measures), obtained PLEs predictors (N = 27) and covariates (i.e., age, sex, IQ) were included in the classification model based on Elastic Net algorithm for predicting high/low PLEs in 396 healthy participants aged 14-24 (M_age = 19.72 ± 2.5). We externally validated PLE-related predictors in a clinical sample comprising first-episode psychosis patients (n = 19), their siblings (n = 20), and healthy controls (n = 19).

Eleven factors, including environmental and cognitive appraisals, along with 16 structural network properties spanning frontal, temporal, occipital, and parietal regions, were identified as important predictors of PLEs. The model's performance was moderate in predicting low versus high PLEs (accuracy = 75%, AUC = 0.750). Specificity was high (84.2%) in distinguishing siblings from patients.

Multimodal features, including environmental burden, cognitive schemas, and brain network alterations, predict PLEs and partially generalize to clinical psychosis. These variables may reflect intermediate phenotypes across the psychosis spectrum, offering insights into both vulnerability and resilience.