Abstract
Brain-age prediction is a novel approach to assessing deviated brain aging trajectories in different diseases. However, most studies have used an average brain age gap (BAG) of individuals with schizophrenia of different illness durations for comparison with healthy participants. Therefore, this study investigated whether declined brain structures as reflected by BAGs may be present in schizophrenia in terms of brain volume, cortical thickness, and fractional anisotropy across different illness durations. We used brain volume, cortical thickness, and fractional anisotropy as features to train three models from the training dataset. Three models were applied to predict brain ages in the hold-out test and schizophrenia datasets and calculate BAGs. We divided the schizophrenia dataset into multiple groups based on the illness duration using a sliding time window approach for ANCOVA analysis. The brain volume and cortical thickness models revealed that, in comparison with healthy controls, individuals with schizophrenia had larger BAGs across different illness durations, whereas the BAG in terms of fractional anisotropy did not differ from that of healthy controls after disease onset. Moreover, the BAG at the initial stage of schizophrenia was the largest in the cortical thickness model. In contrast, the BAG from approximately two decades after disease onset was the largest in the brain volume model. Our findings suggest that schizophrenia differentially affects the decline of different brain structures during the disease course. Moreover, different trends of decline in thickness and volume-based measures suggest a differential decline in dimensions of brain structure throughout the course of schizophrenia.