Age-Dependent Corpus Callosum Thickness Abnormalities and Clinical Implications in Treatment-Naïve First-Episode Schizophrenia

Background: Although morphological abnormalities of the corpus callosum (CC) have been reported in schizophrenia, findings across studies have been inconsistent. We systematically examined whether these morphological alterations are influenced by age. Methods: A total of 151 individuals with treatment-naïve first-episode schizophrenia (FES) and 278 healthy controls were included. T1-weighted structural MRI scans were used to segment the CC on the midsagittal plane into 100 equidistant points, and CC thickness was estimated at each point. To determine whether CC thickness abnormalities associated with schizophrenia were moderated by age, we applied the Johnson-Neyman technique. Additionally, we investigated the relationship between age-dependent CC thickness abnormalities and clinical symptoms using partial least-squares correlation analysis. Results: Abnormal CC thickness was observed in individuals with treatment-naïve FES, specifically within the rostral body, anterior midbody, isthmus, and splenium. These regions were thinner in younger patients compared with healthy controls but appeared thicker in older patients. Furthermore, increased CC thickness in older patients was associated with greater clinical symptom severity, whereas this association was not observed in younger patients. Conclusions: Our findings demonstrate that CC thickness abnormalities in treatment-naïve FES are age-dependent. The relationship between CC thickness and symptom severity also varies as a function of age. These results suggest that the CC may represent a critical biological target for age-sensitive, individualized therapeutic interventions in schizophrenia.