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Is treatment-resistant schizophrenia associated with distinct neurobiological callosal connectivity abnormalities?

Published online by Cambridge University Press:  10 August 2020

Idaiane Batista Assunção-Leme
Affiliation:
Laboratório Interdisciplinar de Neurociências Clínicas (LiNC), Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil Departamento de Psiquiatria, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil
André Zugman
Affiliation:
Laboratório Interdisciplinar de Neurociências Clínicas (LiNC), Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil Departamento de Psiquiatria, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil
Luciana Monteiro de Moura
Affiliation:
Hospital Israelita Albert Einstein, São Paulo, Brazil Departamento de Diagnóstico por Imagem, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil
João Ricardo Sato
Affiliation:
Laboratório Interdisciplinar de Neurociências Clínicas (LiNC), Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil Center of Mathematics, Computing and Cognition, Universidade Federal do ABC (UFABC), Santo André, Brazil
Cinthia Higuchi
Affiliation:
Laboratório Interdisciplinar de Neurociências Clínicas (LiNC), Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil Departamento de Psiquiatria, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil
Bruno Bertolucci Ortiz
Affiliation:
Laboratório Interdisciplinar de Neurociências Clínicas (LiNC), Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil Departamento de Psiquiatria, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil Programa de Esquizofrenia, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil
Cristiano Noto
Affiliation:
Laboratório Interdisciplinar de Neurociências Clínicas (LiNC), Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil Departamento de Psiquiatria, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil Programa de Esquizofrenia, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil
Vanessa Kiyomi Ota
Affiliation:
Laboratório Interdisciplinar de Neurociências Clínicas (LiNC), Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil Departamento de Psiquiatria, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil
Sintia Iole Belangero
Affiliation:
Laboratório Interdisciplinar de Neurociências Clínicas (LiNC), Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil Departamento de Psiquiatria, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil
Rodrigo A. Bressan
Affiliation:
Laboratório Interdisciplinar de Neurociências Clínicas (LiNC), Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil Departamento de Psiquiatria, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil Programa de Esquizofrenia, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil
Nicolas A. Crossley
Affiliation:
Department of Psychiatry, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile Biomedical Imaging Center and Center for Integrative Neuroscience, Pontificia Universidad Católica de Chile, Santiago, Chile Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neurosciences, King’s College London, London, United Kingdom
Andrea P. Jackowski
Affiliation:
Laboratório Interdisciplinar de Neurociências Clínicas (LiNC), Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil Departamento de Psiquiatria, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil
Ary Gadelha
Affiliation:
Laboratório Interdisciplinar de Neurociências Clínicas (LiNC), Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil Departamento de Psiquiatria, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil Programa de Esquizofrenia, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil
Corresponding

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.

Type
Original Research
Copyright
© The Author(s), 2020. Published by Cambridge University Press

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Footnotes

Andrea P. Jackowski and Ary Gadelha had the same level of contribution.

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