Abstract
Background/Objectives: Schizophrenia (SZ) is a complex psychiatric disorder characterized by neurodegenerative processes, but the structural brain alterations associated with its progression remain poorly understood. This study investigated structural brain changes in SZ, particularly in the fronto-temporal and limbic regions, and explored their relationship with symptom severity, with a focus on mood- and emotion-related symptoms. Methods: We analyzed structural MRI data from 74 SZ patients and 91 healthy controls (HCs) using voxel-based morphometry (VBM) to compare whole-brain grey matter volumes (GMVs). The analysis focused on the fronto-temporal and limbic regions, and correlations between GMV and symptom severity were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Generalized Psychopathology (GP) scale. Results: SZ patients exhibited significant reductions in GMV in the fronto-temporal and limbic regions, including the dorsolateral prefrontal cortex (dlPFC) and the temporal pole, compared to HCs. Notably, a significant positive association was found between GMV in the right inferior temporal gyrus (ITG) and the severity of generalized psychopathology, as well as with anxiety, depression, mannerisms, and unusual thought content. Further post hoc analysis identified a specific cluster of mood-related symptoms contributing to the GP scale, which correlated with GMV changes in the right ITG. Conclusions: Our findings provide new evidence of structural brain alterations in SZ, particularly in the fronto-temporal and limbic regions, suggesting a progressive neurodegenerative pattern. The role of the right ITG in mood- and emotion-related symptoms requires further exploration, as it could offer insights into SZ pathophysiology and aid in distinguishing SZ from other mood-related disorders.