Deep Learning-based Brain Age Prediction in Patients With Schizophrenia Spectrum Disorders

Background and Hypothesis: The brain-predicted age difference (brain-PAD) may serve as a biomarker for neurodegeneration. We investigated the brain-PAD in patients with schizophrenia (SCZ), first-episode schizophrenia spectrum disorders (FE-SSDs), and treatment-resistant schizophrenia (TRS) using structural magnetic resonance imaging (sMRI). Study Design: We employed a convolutional network-based regression (SFCNR), and compared its performance with models based on three machine learning (ML) algorithms. We pretrained the SFCNR with sMRI data of 7590 healthy controls (HCs) selected from the UK Biobank. The parameters of the pretrained model were transferred to the next training phase with a new set of HCs (n = 541). The brain-PAD was analyzed in independent HCs (n = 209) and patients (n = 233). Correlations between the brain-PAD and clinical measures were investigated. Study Results: The SFCNR model outperformed three commonly used ML models. Advanced brain aging was observed in patients with SCZ, FE-SSDs, and TRS compared to HCs. A significant difference in brain-PAD was observed between FE-SSDs and TRS with ridge regression but not with the SFCNR model. Chlorpromazine equivalent dose and cognitive function were correlated with the brain-PAD in SCZ and FE-SSDs. Conclusions: Our findings indicate that there is advanced brain aging in patients with SCZ and higher brain-PAD in SCZ can be used as a surrogate marker for cognitive dysfunction. These findings warrant further investigations on the causes of advanced brain age in SCZ. In addition, possible psychosocial and pharmacological interventions targeting brain health should be considered in early-stage SCZ patients with advanced brain age.