Cao H, Wei X, Hu N, et al. - Previous studies have described that cerebello-thalamo-cortical (CTC) hyperconnectivity is possibly a state-independent neural signature for psychosis. Findings herein yield initial evidence suggesting an individualized diagnostic and prognostic value of the putative “CTC hyperconnectivity” anomaly for schizophrenia, and highlight the potential of this measure in precision psychiatry.

• fMRI as well as clinical data obtained from 214 untreated first-episode patients with schizophrenia (62 of whom were clinically followed-up at least once at the 12th and 24th months after treatment initiation) and 179 healthy controls were used.

• Patients had significantly increased baseline CTC connectivity, which remained stable after treatment.

• Via conducting cross-validated LASSO regression, measures of CTC connectivity were identified to discriminate patients from controls with moderate classification accuracy.

• The classification model showed good generalizability in the independent sample of 42 untreated first-episode patients and 65 controls.

• Significant predictive value of higher CTC connectivity at baseline for poorer long-term symptom reduction in negative symptoms but not positive or general symptoms.