Derivation and utility of schizophrenia polygenic risk associated multimodal MRI frontotemporal network

Schizophrenia is a highly heritable psychiatric disorder characterized by widespread functional and structural brain abnormalities. However, previous association studies between MRI and polygenic risk were mostly ROI-based single modality analyses, rather than identifying brain-based multimodal predictive biomarkers. Based on schizophrenia polygenic risk scores (PRS) from healthy white people within the UK Biobank dataset (N = 22,459), we discovered a robust PRS-associated brain pattern with smaller gray matter volume and decreased functional activation in frontotemporal cortex, which distinguished schizophrenia from controls with >83% accuracy, and predicted cognition and symptoms across 4 independent schizophrenia cohorts. Further multi-disease comparisons demonstrated that these identified frontotemporal alterations were most severe in schizophrenia and schizo-affective patients, milder in bipolar disorder, and indistinguishable from controls in autism, depression and attention-deficit hyperactivity disorder. These findings indicate the potential of the identified PRS-associated multimodal frontotemporal network to serve as a trans-diagnostic gene intermediated brain biomarker specific to schizophrenia. Schizophrenia is highly heritable and characterized by widespread brain abnormalities. Here, the authors identify schizophrenia polygenic risk associated multimodal frontotemporal network that can serve as a transdiagnostic brain signature specific to schizophrenia.

Automated summary

Schizophrenia is a highly heritable psychiatric disorder characterized by widespread brain abnormalities. This study identifies a multimodal frontotemporal network associated with schizophrenia polygenic risk, serving as a specific brain biomarker for schizophrenia.