Resting-State Functional Connectivity Explained Psychotic-like Experiences in the General Population and Partially Generalized to Patients and Relatives

Background: Psychotic-like experiences (PLEs) are considered the subclinical portion of the psychosis continuum. Research suggests that there are resting-state functional connectivity (rsFC) substrates of PLEs, yet it is unclear if the same substrates underlie more severe psychosis. Here, to our knowledge, we report the first study to build a cross-validated rsFC model of PLEs in a large community sample and directly test its ability to explain psychosis in an independent sample of patients with psychosis and their relatives. Methods: Resting-state FC of 855 healthy young adults from the WU-Minn Human Connectome Project (HCP) was used to predict PLEs with elastic net. An rsFC composite score based on the resulting model was correlated with psychotic traits and symptoms in 118 patients with psychosis, 71 nonpsychotic first-degree relatives, and 45 healthy control subjects from the psychosis HCP. Results: In the HCP, the cross-validated model explained 3.3% of variance in PLEs. Predictive connections spread primarily across the default, frontoparietal, cingulo-opercular, and dorsal attention networks. The model partially generalized to a younger, but not older, subsample in the psychosis HCP, explaining two measures of positive/disorganized psychotic traits (the Structured Interview for Schizotypy: β = 0.25, p_one-tailed = .027; the Schizotypy Personality Questionnaire positive factor: β = 0.14, p_one-tailed = .041). However, it did not differentiate patients from relatives and control subjects or explain psychotic symptoms in patients. Conclusions: Some rsFC substrates of PLEs are shared across the psychosis continuum. However, explanatory power was modest, and generalization was partial. It is equally important to understand shared versus distinct rsFC variances across the psychosis continuum.