Patterns of regional gray matter loss at different stages of schizophrenia: A multisite, cross-sectional VBM study in first-episode and chronic illness
Background: Structural brain abnormalities in schizophrenia have been repeatedly demonstrated in magnetic resonance imaging (MRI) studies, but it remains unclear whether these are static or progressive in nature. While longitudinal MRI studies have been traditionally used to assess the issue of prog...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2016-01-01
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| Series: | NeuroImage: Clinical |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213158216301000 |
| _version_ | 1818011311913566208 |
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| author | Ulysses S. Torres Fabio L.S. Duran Maristela S. Schaufelberger José A.S. Crippa Mario R. Louzã Paulo C. Sallet Caroline Y.O. Kanegusuku Helio Elkis Wagner F. Gattaz Débora P. Bassitt Antonio W. Zuardi Jaime Eduardo C. Hallak Claudia C. Leite Claudio C. Castro Antonio Carlos Santos Robin M. Murray Geraldo F. Busatto |
| author_facet | Ulysses S. Torres Fabio L.S. Duran Maristela S. Schaufelberger José A.S. Crippa Mario R. Louzã Paulo C. Sallet Caroline Y.O. Kanegusuku Helio Elkis Wagner F. Gattaz Débora P. Bassitt Antonio W. Zuardi Jaime Eduardo C. Hallak Claudia C. Leite Claudio C. Castro Antonio Carlos Santos Robin M. Murray Geraldo F. Busatto |
| author_sort | Ulysses S. Torres |
| collection | DOAJ |
| description | Background: Structural brain abnormalities in schizophrenia have been repeatedly demonstrated in magnetic resonance imaging (MRI) studies, but it remains unclear whether these are static or progressive in nature. While longitudinal MRI studies have been traditionally used to assess the issue of progression of brain abnormalities in schizophrenia, information from cross-sectional neuroimaging studies directly comparing first-episode and chronic schizophrenia patients to healthy controls may also be useful to further clarify this issue. With the recent interest in multisite mega-analyses combining structural MRI data from multiple centers aiming at increased statistical power, the present multisite voxel-based morphometry (VBM) study was carried out to examine patterns of brain structural changes according to the different stages of illness and to ascertain which (if any) of such structural abnormalities would be specifically correlated to potential clinical moderators, including cumulative exposure to antipsychotics, age of onset, illness duration and overall illness severity.
Methods: We gathered a large sample of schizophrenia patients (161, being 99 chronic and 62 first-episode) and controls (151) from four previous morphometric MRI studies (1.5 T) carried out in the same geographical region of Brazil. Image processing and analyses were conducted using Statistical Parametric Mapping (SPM8) software with the diffeomorphic anatomical registration through exponentiated Lie algebra (DARTEL) algorithm. Group effects on regional gray matter (GM) volumes were investigated through whole-brain voxel-wise comparisons using General Linear Model Analysis of Co-variance (ANCOVA), always including total GM volume, scan protocol, age and gender as nuisance variables. Finally, correlation analyses were performed between the aforementioned clinical moderators and regional and global brain volumes.
Results: First-episode schizophrenia subjects displayed subtle volumetric deficits relative to controls in a circumscribed brain regional network identified only in small volume-corrected (SVC) analyses (p < 0.05, FWE-corrected), including the insula, temporolimbic structures and striatum. Chronic schizophrenia patients, on the other hand, demonstrated an extensive pattern of regional GM volume decreases relative to controls, involving bilateral superior, inferior and orbital frontal cortices, right middle frontal cortex, bilateral anterior cingulate cortices, bilateral insulae and right superior and middle temporal cortices (p < 0.05, FWE-corrected over the whole brain). GM volumes in several of those brain regions were directly correlated with age of disease onset on SVC analyses for conjoined (first-episode and chronic) schizophrenia groups. There were also widespread foci of significant negative correlation between duration of illness and relative GM volumes, but such findings remained significant only for the right dorsolateral prefrontal cortex after accounting for the influence of age of disease onset. Finally, significant negative correlations were detected between life-time cumulative exposure to antipsychotics and total GM and white matter volumes in schizophrenia patients, but no significant relationship was found between indices of antipsychotic usage and relative GM volume in any specific brain region.
Conclusion: The above data indicate that brain changes associated with the diagnosis of schizophrenia are more widespread in chronic schizophrenia compared to first-episode patients. Our findings also suggest that relative GM volume deficits may be greater in (presumably more severe) cases with earlier age of onset, as well as varying as a function of illness duration in specific frontal brain regions. Finally, our results highlight the potentially complex effects of the continued use of antipsychotic drugs on structural brain abnormalities in schizophrenia, as we found that cumulative doses of antipsychotics affected brain volumes globally rather than selectively on frontal-temporal regions. |
| first_indexed | 2024-04-14T06:07:06Z |
| format | Article |
| id | doaj.art-ef399817feda4c30a512345dd1739390 |
| institution | Directory Open Access Journal |
| issn | 2213-1582 |
| language | English |
| last_indexed | 2024-04-14T06:07:06Z |
| publishDate | 2016-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | NeuroImage: Clinical |
| spelling | doaj.art-ef399817feda4c30a512345dd17393902022-12-22T02:08:31ZengElsevierNeuroImage: Clinical2213-15822016-01-0112C11510.1016/j.nicl.2016.06.002Patterns of regional gray matter loss at different stages of schizophrenia: A multisite, cross-sectional VBM study in first-episode and chronic illnessUlysses S. Torres0Fabio L.S. Duran1Maristela S. Schaufelberger2José A.S. Crippa3Mario R. Louzã4Paulo C. Sallet5Caroline Y.O. Kanegusuku6Helio Elkis7Wagner F. Gattaz8Débora P. Bassitt9Antonio W. Zuardi10Jaime Eduardo C. Hallak11Claudia C. Leite12Claudio C. Castro13Antonio Carlos Santos14Robin M. Murray15Geraldo F. Busatto16Post-Graduation Program in Radiology, Institute of Radiology (INRAD), Faculty of Medicine, University of São Paulo, BrazilLaboratory of Psychiatric Neuroimaging (LIM-21), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, BrazilLaboratory of Psychiatric Neuroimaging (LIM-21), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, BrazilCenter for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, BrazilDepartment and Institute of Psychiatry, University of Sao Paulo Medical School, BrazilCenter for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, BrazilDepartment and Institute of Psychiatry, University of Sao Paulo Medical School, BrazilDepartment and Institute of Psychiatry, University of Sao Paulo Medical School, BrazilCenter for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, BrazilDepartment and Institute of Psychiatry, University of Sao Paulo Medical School, BrazilCenter for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, BrazilCenter for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, BrazilPost-Graduation Program in Radiology, Institute of Radiology (INRAD), Faculty of Medicine, University of São Paulo, BrazilPost-Graduation Program in Radiology, Institute of Radiology (INRAD), Faculty of Medicine, University of São Paulo, BrazilCenter for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, BrazilDepartment of Psychosis Studies, Institute of Psychiatry, King's College London, UKPost-Graduation Program in Radiology, Institute of Radiology (INRAD), Faculty of Medicine, University of São Paulo, BrazilBackground: Structural brain abnormalities in schizophrenia have been repeatedly demonstrated in magnetic resonance imaging (MRI) studies, but it remains unclear whether these are static or progressive in nature. While longitudinal MRI studies have been traditionally used to assess the issue of progression of brain abnormalities in schizophrenia, information from cross-sectional neuroimaging studies directly comparing first-episode and chronic schizophrenia patients to healthy controls may also be useful to further clarify this issue. With the recent interest in multisite mega-analyses combining structural MRI data from multiple centers aiming at increased statistical power, the present multisite voxel-based morphometry (VBM) study was carried out to examine patterns of brain structural changes according to the different stages of illness and to ascertain which (if any) of such structural abnormalities would be specifically correlated to potential clinical moderators, including cumulative exposure to antipsychotics, age of onset, illness duration and overall illness severity. Methods: We gathered a large sample of schizophrenia patients (161, being 99 chronic and 62 first-episode) and controls (151) from four previous morphometric MRI studies (1.5 T) carried out in the same geographical region of Brazil. Image processing and analyses were conducted using Statistical Parametric Mapping (SPM8) software with the diffeomorphic anatomical registration through exponentiated Lie algebra (DARTEL) algorithm. Group effects on regional gray matter (GM) volumes were investigated through whole-brain voxel-wise comparisons using General Linear Model Analysis of Co-variance (ANCOVA), always including total GM volume, scan protocol, age and gender as nuisance variables. Finally, correlation analyses were performed between the aforementioned clinical moderators and regional and global brain volumes. Results: First-episode schizophrenia subjects displayed subtle volumetric deficits relative to controls in a circumscribed brain regional network identified only in small volume-corrected (SVC) analyses (p < 0.05, FWE-corrected), including the insula, temporolimbic structures and striatum. Chronic schizophrenia patients, on the other hand, demonstrated an extensive pattern of regional GM volume decreases relative to controls, involving bilateral superior, inferior and orbital frontal cortices, right middle frontal cortex, bilateral anterior cingulate cortices, bilateral insulae and right superior and middle temporal cortices (p < 0.05, FWE-corrected over the whole brain). GM volumes in several of those brain regions were directly correlated with age of disease onset on SVC analyses for conjoined (first-episode and chronic) schizophrenia groups. There were also widespread foci of significant negative correlation between duration of illness and relative GM volumes, but such findings remained significant only for the right dorsolateral prefrontal cortex after accounting for the influence of age of disease onset. Finally, significant negative correlations were detected between life-time cumulative exposure to antipsychotics and total GM and white matter volumes in schizophrenia patients, but no significant relationship was found between indices of antipsychotic usage and relative GM volume in any specific brain region. Conclusion: The above data indicate that brain changes associated with the diagnosis of schizophrenia are more widespread in chronic schizophrenia compared to first-episode patients. Our findings also suggest that relative GM volume deficits may be greater in (presumably more severe) cases with earlier age of onset, as well as varying as a function of illness duration in specific frontal brain regions. Finally, our results highlight the potentially complex effects of the continued use of antipsychotic drugs on structural brain abnormalities in schizophrenia, as we found that cumulative doses of antipsychotics affected brain volumes globally rather than selectively on frontal-temporal regions.http://www.sciencedirect.com/science/article/pii/S2213158216301000Voxel-based morphometryMRISchizophrenia |
| spellingShingle | Ulysses S. Torres Fabio L.S. Duran Maristela S. Schaufelberger José A.S. Crippa Mario R. Louzã Paulo C. Sallet Caroline Y.O. Kanegusuku Helio Elkis Wagner F. Gattaz Débora P. Bassitt Antonio W. Zuardi Jaime Eduardo C. Hallak Claudia C. Leite Claudio C. Castro Antonio Carlos Santos Robin M. Murray Geraldo F. Busatto Patterns of regional gray matter loss at different stages of schizophrenia: A multisite, cross-sectional VBM study in first-episode and chronic illness NeuroImage: Clinical Voxel-based morphometry MRI Schizophrenia |
| title | Patterns of regional gray matter loss at different stages of schizophrenia: A multisite, cross-sectional VBM study in first-episode and chronic illness |
| title_full | Patterns of regional gray matter loss at different stages of schizophrenia: A multisite, cross-sectional VBM study in first-episode and chronic illness |
| title_fullStr | Patterns of regional gray matter loss at different stages of schizophrenia: A multisite, cross-sectional VBM study in first-episode and chronic illness |
| title_full_unstemmed | Patterns of regional gray matter loss at different stages of schizophrenia: A multisite, cross-sectional VBM study in first-episode and chronic illness |
| title_short | Patterns of regional gray matter loss at different stages of schizophrenia: A multisite, cross-sectional VBM study in first-episode and chronic illness |
| title_sort | patterns of regional gray matter loss at different stages of schizophrenia a multisite cross sectional vbm study in first episode and chronic illness |
| topic | Voxel-based morphometry MRI Schizophrenia |
| url | http://www.sciencedirect.com/science/article/pii/S2213158216301000 |
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