Biosignatures of cognitive basic symptoms mark a distinct neurodevelopmental pathway to schizophrenia - PubMed
5 hours ago
- #neuroimaging
- #psychosis-risk
- #schizophrenia
- Cognitive basic symptoms (COGDIS) are closely aligned with schizophrenia's core features, such as formal thought disorder, but have been underutilized in risk prediction.
- Machine learning applied to structural MRI data from 1,425 patients and 907 healthy controls compared brain signatures of different clinical-high-risk (CHR-P) definitions.
- The COGDIS brain signature distinguished patients from controls (BAC=69%) and aligned with the schizophrenia signature (r = 0.60), involving shared fronto-parieto-perisylvian volume reductions.
- Ultra-high-risk (UHR) symptoms were linked to a weak and diagnostically unspecific brain pattern, characterized by volume enlargements.
- The MIXED phenotype (overlap of COGDIS and UHR) showed a dimensional, transdiagnostic signature enriched across early psychotic and affective disease states.
- COGDIS and schizophrenia signature expressions were predictable based on polygenic, cognitive, and exposomal factors, with 12%-21% variance explained.
- COGDIS and schizophrenia brain scores stratified patients with functional disability, while UHR scores predicted better outcomes.
- The findings support a biologically informed reconceptualization of psychosis risk, with COGDIS capturing a core liability dimension of schizophrenia.