MARISTELA SCHAUFELBERGER SPANGHERO
Projetos de Pesquisa
Unidades Organizacionais
Instituto de Psiquiatria, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/21 - Laboratório de Neuroimagem em Psiquiatria, Hospital das Clínicas, Faculdade de Medicina
LIM/21 - Laboratório de Neuroimagem em Psiquiatria, Hospital das Clínicas, Faculdade de Medicina
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conferenceObject Brain Structure and the Prediction of Outcome in First-Episode Schizophrenia-Spectrum Disorders and Affective Psychosis: A Population-Based Study(2012) ROSA, Pedro G.; SCHALFELBERGER, Maristela S.; DURAN, Fabio L. S.; SANTOS, Luciana C.; MENEZES, Paulo R.; SCAZUFCA, Marcia; MURRAY, Robin M.; BUSATTO, Geraldo F.Background: MRI studies of the prediction of outcome among subjects with first-episode psychosis (FEP) have brought misleading evidence to discussion. Cognitive impairment in subjects with psychosis is receiving particular attention, and may be the symptom dimension most associated with outcome in those patients. Methods: Structural MRI on a FEP (N=96) sample with subjects with schizophrenia-spectrum disorders (N=55) and affective psychoses (N=41). Outcome evaluation after a median period of one year consisted on PANSS, cognitive measures (verbal fluency and digit spans) and disability evaluation (WHO-DAS). Lateral ventricles, studied using a region of interest approach, and regional GM, analyzed using VBM with SPM, at the baseline entered statistics as predictive of outcome at the follow-up. Results: Frontal and temporal cortices GM volume were associated with outcome measures, in particular with the performance o cognitive tasks, in the overall FEP Group and in the subgroups (schizophrenia and affective psychoses). Particularly, the affective psychosis subgroup showed more robust associations of GM volumes with outcome measures than the schizophrenia-spectrum subgroup. Furthermore, temporal horns measures were negatively correlated with digit spans’ performances in the FEP group and in the subgroups. None of these findings could be attributed to confounding factors, such as outcome measures at baseline and antipsychotic intake. Conclusions: Brain structure at the moment of the first-episode of psychosis of patients with schizophrenia and subjects with affective psychoses was associated with outcome, particularly cognitive measures. The predominance of findings on frontal-temporal regions is compatible with the presence of a fronto-temporal disconnectivity underlying psychoses. Keyword(s): Schizophrenia, Bipolar Disorder, Neuroimaging, Outcome, Cognition- Patterns of regional gray matter loss at different stages of schizophrenia: A multisite, cross-sectional VBM study in first-episode and chronic illness(2016) TORRES, Ulysses S.; DURAN, Fabio L. S.; SCHAUFELBERGER, Maristela S.; CRIPPA, Jose A. S.; LOUZA, Mario R.; SALLET, Paulo C.; KANEGUSUKU, Caroline Y. O.; ELKIS, Helio; GATTAZ, Wagner F.; BASSITT, Debora P.; ZUARDI, AntonioW.; HALLAK, Jaime Eduardo C.; LEITE, Claudia C.; CASTRO, Claudio C.; SANTOS, Antonio Carlos; MURRAY, Robin M.; BUSATTO, Geraldo F.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 longitudinalMRI 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-basedmorphometry (VBM) studywas carried out to examine patterns of brain structural changes according to the different stages of illness and to ascertainwhich (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: Wegathered a large sample of schizophrenia patients (161, being 99 chronic and 62 first-episode) and controls (151) fromfour previousmorphometricMRI 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 LinearModel Analysis of Co-variance (ANCOVA), always including total GMvolume, scan protocol, age and gender as nuisance variables. Finally, correlation analyseswere 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 regionswere 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. (C) 2016 The Authors.
conferenceObject CHARACTERISTICS OF A CATCHMENT AREA IN THE STATE OF SAO PAULO, BRAZIL, FOR CONDUCTING AN INCIDENCE STUDY OF SCHIZOPHRENIA AND OTHER PSYCHOTIC DISORDERS(2014) TENAN, Silvia H.; SCHAUFELBERGER, Maristela S.; SHUHAMA, Rosana; SOUZA, Juliana; SANTOS, Jair; BUSATTO, Geraldo; MORGAN, Craig; OS, Jim van; BEN, Cristina Del; MENEZES, PauloconferenceObject PRELIMINARY SAMPLE DESCRIPTION OF FIRST EPISODE PSYCHOSIS IN A BRAZILIAN LARGE CATCHMENT AREA(2014) SHUHAMA, Rosana; TENAN, Silvia; SOUZA, Juliana; SCHAUFELBERGER, Maristela S.; LOUZADA-JUNIOR, Paulo; SANTOS, Antonio; MORGAN, Craig; OS, Jim Van; MENEZES, Paulo; DEL-BEN, CristinaconferenceObject Structural Brain Changes in First-Episode Schizophrenia: A 4-5 Year Follow-Up Study Using MRI(2012) SCHALFELBERGER, Maristela S.; ROSA, Pedro G. P.; DURAN, Fabio L. S.; MENEZES, Paulo R.; SCAZUFCA, Marcia; MURRAY, Robin M.; BUSATTO, Geraldo F.Background: The presence of progressive structural brain changes over the first years of disease in first-episode schizophrenia (FES) patients is still controversial. The supposed progression of brain abnormalities in these patients may be associated with outcome and with antipsychotic exposure. Methods: Longitudinal population-based study performed in São Paulo - Brazil. Longitudinal analysis of GM matter volume using SPM was performed in 32 FES and 34 controls 4-5 years after baseline. Outcome measures were assessed by clinical course of symptoms (DSM-IV) and by global functioning (GAF scores). Results: FES did not differ from controls regarding GM changes over time, but those that remained psychotic and had lower global functioning over the follow-up period had GM concentration reduction in the left insula and in the left superior temporal gyrus in comparison to controls. Medication status had no effect on GM volumetric changes. Conclusions: Our findings suggest that a poor outcome, with chronic symptoms and a poor global functioning over 4-5 years after the first episode of psychosis is associated with brain abnormalities progression in brain regions which showed GM reduction at baseline (Schaufelberger et al, 2007). These results suggest that the progressive hypothesis in schizophrenia is probably not valid to all subjects that suffer from this illness.- Longitudinal follow-up of cavum septum pellucidum and adhesio interthalamica alterations in first-episode psychosis: a population-based MRI study(2012) TRZESNIAK, C.; SCHAUFELBERGER, M. S.; DURAN, F. L. S.; SANTOS, L. C.; ROSA, P. G. P.; MCGUIRE, P. K.; MURRAY, R. M.; SCAZUFCA, M.; MENEZES, P. R.; HALLAK, J. E. C.; CRIPPA, J. A. S.; BUSATTO, G. F.Background. Neurodevelopmental alterations have been described inconsistently in psychosis probably because of lack of standardization among studies. The aim of this study was to conduct the first longitudinal and population-based magnetic resonance imaging (MRI) evaluation of the presence and size of the cavum septum pellucidum (CSP) and adhesio interthalamica (AI) in a large sample of patients with first-episode psychosis (FEP). Method. FEP patients (n=122) were subdivided into schizophrenia (n=62), mood disorders (n=46) and other psychosis (n=14) groups and compared to 94 healthy next-door neighbour controls. After 13 months, 80 FEP patients and 52 controls underwent a second MRI examination. Results. We found significant reductions in the AI length in schizophrenia FEP in comparison with the mood disorders and control subgroups (longer length) at the baseline assessment, and no differences in any measure of the CSP. By contrast, there was a diagnosis x time interaction for the CSP length, with a more prominent increase for this measure in the psychosis group. There was an involution of the AI length over time for all groups but no diagnosis x time interaction. Conclusions. Our findings suggest that the CSP per se may not be linked to the neurobiology of emerging psychotic disorders, although it might be related to the progression of the disease. However, the fact that the AI length was shown to be shorter at the onset of the disorder supports the neurodevelopmental model of schizophrenia and indicates that an alteration in this grey matter junction may be a risk factor for developing psychosis.
- Multi-center MRI prediction models: Predicting sex and illness course in first episode psychosis patients(2017) NIEUWENHUIS, Mireille; SCHNACK, Hugo G.; HAREN, Neeltje E. van; LAPPIN, Julia; MORGAN, Craig; REINDERS, Antje A.; GUTIERREZ-TORDESILLAS, Diana; ROIZ-SANTIANEZ, Roberto; SCHAUFELBERGER, Maristela S.; ROSA, Pedro G.; ZANETTI, Marcus V.; BUSATTO, Geraldo F.; CRESPO-FACORRO, Benedicto; MCGORRY, Patrick D.; VELAKOULIS, Dennis; PANTELIS, Christos; WOOD, Stephen J.; KAHN, Rene S.; MOURAO-MIRANDA, Janaina; DAZZAN, PaolaStructural Magnetic Resonance Imaging (MRI) studies have attempted to use brain measures obtained at the first-episode of psychosis to predict subsequent outcome, with inconsistent results. Thus, there is a real need to validate the utility of brain measures in the prediction of outcome using large datasets, from independent samples, obtained with different protocols and from different MRI scanners. This study had three main aims: 1) to investigate whether structural MRI data from multiple centers can be combined to create a machine-leaming model able to predict a strong biological variable like sex; 2) to replicate our previous finding that an MRI scan obtained at first episode significantly predicts subsequent illness course in other independent datasets; and finally, 3) to test whether these datasets can be combined to generate multicenter models with better accuracy in the prediction of illness course. The multi-center sample included brain structural MRI scans from 256 males and 133 females patients with first episode psychosis, acquired in five centers: University Medical Center Utrecht (The Netherlands) (n = 67); Institute of Psychiatry, Psychology and Neuroscience, London (United Kingdom) (n = 97); University of Sao Paulo (Brazil) (n = 64); University of Cantabria, Santander (Spain) (n = 107); and University of Melbourne (Australia) (n = 54). All images were acquired on 1.5-Tesla scanners and all centers provided information on illness course during a follow-up period ranging 3 to 7 years. We only included in the analyses of outcome prediction patients for whom illness course was categorized as either ""continuous"" (n = 94) or ""remitting"" (n = 118). Using structural brain scans from all centers, sex was predicted with significant accuracy (89%; p < 0.001). In the single- or multi-center models, illness course could not be predicted with significant accuracy. However, when reducing heterogeneity by restricting the analyses to male patients only, classification accuracy improved in some samples. This study provides proof of concept that combining multi-center MRI data to create a well performing classification model is possible. However, to create complex multi-center models that perform accurately, each center should contribute a sample either large or homogeneous enough to first allow accurate classification within the single-center. (C) 2016 The Authors.
- Cortical abnormalities in bipolar disorder: an MRI analysis of 6503 individuals from the ENIGMA Bipolar Disorder Working Group(2018) HIBAR, D. P.; WESTLYE, L. T.; DOAN, N. T.; JAHANSHAD, N.; CHEUNG, J. W.; CHING, C. R. K.; VERSACE, A.; BILDERBECK, A. C.; UHLMANN, A.; MWANGI, B.; KRAEMER, B.; OVERS, B.; HARTBERG, C. B.; ABE, C.; DIMA, D.; GROTEGERD, D.; SPROOTEN, E.; BOEN, E.; JIMENEZ, E.; HOWELLS, F. M.; DELVECCHIO, G.; TEMMINGH, H.; STARKE, J.; ALMEIDA, J. R. C.; GOIKOLEA, J. M.; HOUENOU, J.; BEARD, L. M.; RAUER, L.; ABRAMOVIC, L.; BONNIN, M.; PONTEDURO, M. F.; KEIL, M.; RIVE, M. M.; YAO, N.; YALIN, N.; NAJT, P.; ROSA, P. G.; REDLICH, R.; TROST, S.; HAGENAARS, S.; FEARS, S. C.; ALONSO-LANA, S.; ERP, T. G. M. van; NICKSON, T.; CHAIM-AVANCINI, T. M.; MEIER, T. B.; ELVSASHAGEN, T.; HAUKVIK, U. K.; LEE, W. H.; SCHENE, A. H.; LLOYD, A. J.; YOUNG, A. H.; NUGENT, A.; DALE, A. M.; PFENNIG, A.; MCINTOSH, A. M.; LAFER, B.; BAUNE, B. T.; EKMAN, C. J.; ZARATE, C. A.; BEARDEN, C. E.; HENRY, C.; SIMHANDL, C.; MCDONALD, C.; BOURNE, C.; STEIN, D. J.; WOLF, D. H.; CANNON, D. M.; GLAHN, D. C.; VELTMAN, D. J.; POMAROL-CLOTET, E.; VIETA, E.; CANALES-RODRIGUEZ, E. J.; NERY, F. G.; DURAN, F. L. S.; BUSATTO, G. F.; ROBERTS, G.; PEARLSON, G. D.; GOODWIN, G. M.; KUGEL, H.; WHALLEY, H. C.; RUHE, H. G.; SOARES, J. C.; FULLERTON, J. M.; RYBAKOWSKI, J. K.; SAVITZ, J.; CHAIM, K. T.; FATJO-VILAS, M.; SOEIRO-DE-SOUZA, M. G.; BOKS, M. P.; ZANETTI, M. V.; OTADUY, M. C. G.; SCHAUFELBERGER, M. S.; ALDA, M.; INGVAR, M.; PHILLIPS, M. L.; KEMPTON, M. J.; BAUER, M.; LANDEN, M.; LAWRENCE, N. S.; HAREN, N. E. M. van; HORN, N. R.; FREIMER, N. B.; GRUBER, O.; SCHOFIELD, P. R.; MITCHELL, P. B.; KAHN, R. S.; LENROOT, R.; MACHADO-VIEIRA, R.; OPHOFF, R. A.; SARRO, S.; FRANGOU, S.; SATTERTHWAITE, T. D.; HAJEK, T.; DANNLOWSKI, U.; MALT, U. F.; AROLT, V.; GATTAZ, W. F.; DREVETS, W. C.; CASERAS, X.; AGARTZ, I.; THOMPSON, P. M.; ANDREASSEN, O. A.Despite decades of research, the pathophysiology of bipolar disorder (BD) is still not well understood. Structural brain differences have been associated with BD, but results from neuroimaging studies have been inconsistent. To address this, we performed the largest study to date of cortical gray matter thickness and surface area measures from brain magnetic resonance imaging scans of 6503 individuals including 1837 unrelated adults with BD and 2582 unrelated healthy controls for group differences while also examining the effects of commonly prescribed medications, age of illness onset, history of psychosis, mood state, age and sex differences on cortical regions. In BD, cortical gray matter was thinner in frontal, temporal and parietal regions of both brain hemispheres. BD had the strongest effects on left pars opercularis (Cohen's d =-0.293; P = 1.71 x 10(-21)), left fusiform gyrus (d =-0.288; P = 8.25 x 10(-21)) and left rostral middle frontal cortex (d =-0.276; P = 2.99 x 10(-19)). Longer duration of illness (after accounting for age at the time of scanning) was associated with reduced cortical thickness in frontal, medial parietal and occipital regions. We found that several commonly prescribed medications, including lithium, antiepileptic and antipsychotic treatment showed significant associations with cortical thickness and surface area, even after accounting for patients who received multiple medications. We found evidence of reduced cortical surface area associated with a history of psychosis but no associations with mood state at the time of scanning. Our analysis revealed previously undetected associations and provides an extensive analysis of potential confounding variables in neuroimaging studies of BD.
- Cannabis use, cognition and brain structure in first-episode psychosis (vol 147, pg 209, 2013)(2013) CUNHA, Paulo Jannuzzi; ROSA, Pedro Gomes P.; AYRES, Adriana de Mello; DURAN, Fabio L. S.; SANTOS, Luciana C.; SCAZUFCA, Marcia; MENEZES, Paulo R.; SANTOS, Bernardo dos; MURRAY, Robin M.; CRIPPA, Jose Alexandre S.; BUSATTO, Geraldo F.; SCHAUFELBERGER, Maristela S.
conferenceObject CONTINUING GREYMATTER CHANGES IN FIRST-EPISODE SCHIZOPHRENIA AND AFFECTIVE PSYCHOSIS(2014) SCHAUFELBERGER, Maristela S.; ROSA, Pedro; ZANETTI, Marcus; DURAN, Fabio; SANTOS, Luciana; MENEZES, Paulo; SCAZFUCA, Marcia; MURRAY, Robin M.; BUSATTO, Geraldo