Introduction: The corpus callosum (CC) is critical for inter-hemispheric integration, and its structural abnormalities have been implicated in the neurobiology of schizophrenia (SCZ). Ap-proximately 20-35% of SCZ patients exhibit resistance to antipsychotics and are classified as treat-ment-resistant schizophrenia (TRS). To date, no studies have specifically analyzed CC morphology in TRS compared to healthy controls (HCs) and treatment-responsive SCZ patients (non-TRS). Methods: The study included 75 HCs and 97 SCZ patients (39 TRS and 58 non-TRS, including cannabis users and non-users). Participants underwent cross-sectional assessment using the Neuro-logical Evaluation Scale (NES), the Brief Assessment of Cognition in Schizophrenia, and the Posi-tive and Negative Syndrome Scale (PANSS). CC volume was measured via MRI and analyzed with a novel artificial intelligence program (MRI-AI) for single-subject assessment, with findings con-firmed through group-level voxel-based morphometry (VBM). Results: TRS patients exhibited significantly higher total PANSS (p < 0.001) and NES (p < 0.001) scores and performed worse on working memory tasks compared to non-TRS patients. MRI-AI identified CC volume reduction in 55.88% of TRS patients (TRS CC: 3.02 mL vs. non-TRS with cannabis use: 3.69 mL; without cannabis use: 3.28 mL; p = 0.002). VBM confirmed significant CC volume reduction in TRS patients relative to HCs (p = 0.004). Cannabis use in non-TRS patients did not significantly affect CC volume or cognitive performance. Conclusions: TRS is associated with pronounced neurological, cognitive, and clinical dysfunctions. Aberrant CC volume may contribute to TRS pathogenesis and executive function deficits. MRI-AI provides a robust, single-subject approach for characterizing CC abnormalities in schizophrenia, of-fering potential for personalized clinical assessment.
A Case-Control Study On Corpus Callosum Volume and Clinical Correlates in Treatment-Resistant and Responsive Schizophrenia Patients: Addressing MRI Analysis within Single-Subject and a Novel Artificial Intelligence Paradigm / Matrone, M., Romano, A., Kotzalidis, G.D., Perrini, F., Moltoni, G., De Filippis, S., De Persis, S., Pontillo, G., Tranfa, M., Cocozza, S., Brunetti, A., Ciccarelli, M., Vellucci, L., Barone, A., Iasevoli, F., De Bartolomeis, A., Bozzao, A.. - In: CURRENT NEUROPHARMACOLOGY. - ISSN 1570-159X. - 24:(2026). [10.2174/011570159X396695251118094658]
A Case-Control Study On Corpus Callosum Volume and Clinical Correlates in Treatment-Resistant and Responsive Schizophrenia Patients: Addressing MRI Analysis within Single-Subject and a Novel Artificial Intelligence Paradigm
Matrone, Marta;Pontillo, Giuseppe;Tranfa, Mario;Cocozza, Sirio;Brunetti, Arturo;Ciccarelli, Mariateresa;Vellucci, Licia;Barone, Annarita;Iasevoli, Felice;de Bartolomeis, Andrea;
2026
Abstract
Introduction: The corpus callosum (CC) is critical for inter-hemispheric integration, and its structural abnormalities have been implicated in the neurobiology of schizophrenia (SCZ). Ap-proximately 20-35% of SCZ patients exhibit resistance to antipsychotics and are classified as treat-ment-resistant schizophrenia (TRS). To date, no studies have specifically analyzed CC morphology in TRS compared to healthy controls (HCs) and treatment-responsive SCZ patients (non-TRS). Methods: The study included 75 HCs and 97 SCZ patients (39 TRS and 58 non-TRS, including cannabis users and non-users). Participants underwent cross-sectional assessment using the Neuro-logical Evaluation Scale (NES), the Brief Assessment of Cognition in Schizophrenia, and the Posi-tive and Negative Syndrome Scale (PANSS). CC volume was measured via MRI and analyzed with a novel artificial intelligence program (MRI-AI) for single-subject assessment, with findings con-firmed through group-level voxel-based morphometry (VBM). Results: TRS patients exhibited significantly higher total PANSS (p < 0.001) and NES (p < 0.001) scores and performed worse on working memory tasks compared to non-TRS patients. MRI-AI identified CC volume reduction in 55.88% of TRS patients (TRS CC: 3.02 mL vs. non-TRS with cannabis use: 3.69 mL; without cannabis use: 3.28 mL; p = 0.002). VBM confirmed significant CC volume reduction in TRS patients relative to HCs (p = 0.004). Cannabis use in non-TRS patients did not significantly affect CC volume or cognitive performance. Conclusions: TRS is associated with pronounced neurological, cognitive, and clinical dysfunctions. Aberrant CC volume may contribute to TRS pathogenesis and executive function deficits. MRI-AI provides a robust, single-subject approach for characterizing CC abnormalities in schizophrenia, of-fering potential for personalized clinical assessment.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
