Idaiane Batista Assunção-Leme1,2, André Zugman1,2, Luciana Monteiro de Moura3,4, João Ricardo Sato1,5, Cinthia Higuchi1,2, Bruno Bertolucci Ortiz1,2,6, Cristiano Noto1,2,6, Vanessa Kiyomi Ota1,2,7, Sintia Iole Belangero1,2,7, Rodrigo A Bressan1,2,6, Nicolas A Crossley8,9,10, Andrea P Jackowski1,2, Ary Gadelha1,2,6. 1. Laboratório Interdisciplinar de Neurociências Clínicas (LiNC), Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil. 2. Departamento de Psiquiatria, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil. 3. Hospital Israelita Albert Einstein, São Paulo, Brazil. 4. Departamento de Diagnóstico por Imagem, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil. 5. Center of Mathematics, Computing and Cognition, Universidade Federal do ABC (UFABC), Santo André, Brazil. 6. Programa de Esquizofrenia, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil. 7. Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil. 8. Department of Psychiatry, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile. 9. Biomedical Imaging Center and Center for Integrative Neuroscience, Pontificia Universidad Católica de Chile, Santiago, Chile. 10. Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neurosciences, King's College London, London, United Kingdom.
Abstract
BACKGROUND: Resistance to antipsychotic treatment affects up to 30% of patients with schizophrenia. Although the time course of development of treatment-resistant schizophrenia (TRS) varies from patient to patient, the reasons for these variations remain unknown. Growing evidence suggests brain dysconnectivity as a significant feature of schizophrenia. In this study, we compared fractional anisotropy (FA) of brain white matter between TRS and non-treatment-resistant schizophrenia (non-TRS) patients. Our central hypothesis was that TRS is associated with reduced FA values. METHODS: TRS was defined as the persistence of moderate to severe symptoms after adequate treatment with at least two antipsychotics from different classes. Diffusion-tensor brain MRI obtained images from 34 TRS participants and 51 non-TRS. Whole-brain analysis of FA and axial, radial, and mean diffusivity were performed using Tract-Based Spatial Statistics (TBSS) and FMRIB's Software Library (FSL), yielding a contrast between TRS and non-TRS patients, corrected for multiple comparisons using family-wise error (FWE) < 0.05. RESULTS: We found a significant reduction in FA in the splenium of corpus callosum (CC) in TRS when compared to non-TRS. The antipsychotic dose did not relate to the splenium CC. CONCLUSION: Our results suggest that the focal abnormality of CC may be a potential biomarker of TRS.
BACKGROUND: Resistance to antipsychotic treatment affects up to 30% of patients with schizophrenia. Although the time course of development of treatment-resistant schizophrenia (TRS) varies from patient to patient, the reasons for these variations remain unknown. Growing evidence suggests brain dysconnectivity as a significant feature of schizophrenia. In this study, we compared fractional anisotropy (FA) of brain white matter between TRS and non-treatment-resistant schizophrenia (non-TRS) patients. Our central hypothesis was that TRS is associated with reduced FA values. METHODS: TRS was defined as the persistence of moderate to severe symptoms after adequate treatment with at least two antipsychotics from different classes. Diffusion-tensor brain MRI obtained images from 34 TRS participants and 51 non-TRS. Whole-brain analysis of FA and axial, radial, and mean diffusivity were performed using Tract-Based Spatial Statistics (TBSS) and FMRIB's Software Library (FSL), yielding a contrast between TRS and non-TRS patients, corrected for multiple comparisons using family-wise error (FWE) < 0.05. RESULTS: We found a significant reduction in FA in the splenium of corpus callosum (CC) in TRS when compared to non-TRS. The antipsychotic dose did not relate to the splenium CC. CONCLUSION: Our results suggest that the focal abnormality of CC may be a potential biomarker of TRS.