Abstract
Predicting treatment resistance from the first stage of psychosis aids in personalized treatment, promotes a better prognosis, and contributes to healthcare cost savings. Currently, no biomarker accurately predicts treatment resistance in patients with first-episode psychosis (FEP). This study aims to investigate the potential of cortical gyrification as a biomarker for predicting resistance in the first episode of schizophrenia. A cohort of 101 individuals diagnosed with FEP and an equivalent number of age- and sex-matched healthy controls (HCs) underwent T1-weighted magnetic resonance imaging scans immediately after their initial contact. Patients received treatment in a naturalistic clinical setting, and treatment resistance was assessed at the final point after a prolonged follow-up period. A vertex-wise comparison of the local gyrification index (lGI) was conducted among the FEP patients, HCs, and patients classified as treatment-resistant (TRs) and non treatment-resistant (non-TRs). FEP patients showed hypogyria in the paracentral area and a region encompassing the precuneus, cuneus, and lingual gyrus, and the insula compared to HCs. TRs exhibited hypogyria in a region spanning the precuneus, cuneus, and lingual gyrus, while non-TRs displayed hypogyria in the paracentral region. No significant lGI differences were found between TRs and non-TRs; however, after controlling for antipsychotic dosage as a covariate, non-TRs showed hypogyria in the parietal region compared to TRs. The observed disparities in gyrification patterns between TRs and non-TRs suggest the presence of discrete neurodevelopmental anomalies underlying these groups. These findings indicate that cortical gyrification could serve as a biomarker for the early prediction of treatment resistance in psychosis.