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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- Corpus callosum volumes in the 5 years following the first-episode of schizophrenia: Effects of antipsychotics, chronicity and maturation(2018) MOURA, Mariana T. M. de; ZANETTI, Marcus V.; DURAN, Fabio L. S.; SCHAUFELBERGER, Maristela S.; MENEZES, Paulo R.; SCAZUFCA, Marcia; BUSATTO, Geraldo F.; SERPA, Mauricio H.Background: White matter (WM) structural changes, particularly affecting the corpus callosum (CC), seem to be critically implicated in psychosis. Whether such abnormalities are progressive or static is still a matter of debate in schizophrenia research. Aberrant maturation processes might also influence the longitudinal trajectory of age-related CC changes in schizophrenia patients. We investigated whether patients with first-episode schizophreniarelated psychoses (FESZ) would present longitudinal CC and whole WM volume changes over the 5 years after disease onset. Method: Thirty-two FESZ patients and 34 controls recruited using a population-based design completed a 5-year assessment protocol, including structural MRI scanning at baseline and follow-up. The linear effects of disease duration, clinical outcome and antipsychotic (AP) use over time on WM and CC volumes were studied using both voxelwise and volume-based morphometry analyses. We also examined maturation/aging abnormalities through cross-sectional analyses of age-related trajectories of total WM and CC volume changes. Results: No interaction between diagnosis and time was observed, and clinical outcome did not influence CC volumes in patients. On the other hand, FESZ patients continuously exposed to AP medication showed volume increase over time in posterior CC. Curve-estimation analyses revealed a different aging pattern in FESZ patients versus controls: while patients displayed a linear decline of total WM and anterior CC volumes with age, a non-linear trajectory of total WM and relative preservation of CC volumes were observed in controls. Conclusions: Continuous AP exposure can influence CC morphology during the first years after schizophrenia onset. Schizophrenia is associated with an abnormal pattern of total WM and anterior CC aging during nonelderly adulthood, and this adds complexity to the discussion on the static or progressive nature of structural abnormalities in psychosis.
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.
- Voxelwise evaluation of white matter volumes in first-episode psychosis(2012) COLOMBO, Renata Rodrigues da Cunha; SCHAUFELBERGER, Maristela Spanghero; SANTOS, Luciana Cristina; DURAN, Fabio Luis de Souza; MENEZES, Paulo Rossi; SCAZUFCA, Marcia; BUSATTO, Geraldo Filho; ZANETTI, Marcus ViniciusThe occurrence of white matter (WM) abnormalities in psychotic disorders has been suggested by several studies investigating brain pathology and diffusion tensor measures, but evidence assessing regional WM morphometry is still scarce and conflicting. In the present study, 122 individuals with first-episode psychosis (FEP) (62 fulfilling criteria for schizophrenia/schizophreniform disorder, 26 psychotic bipolar I disorder, and 20 psychotic major depressive disorder) underwent magnetic resonance imaging, as well as 94 epidemiologically recruited controls. Images were processed with the Statistical Parametric Mapping (SPM2) package, and voxel-based morphometry was used to compare groups (t-test) and subgroups (ANOVA). Initially, no regional WM abnormalities were observed when both groups (overall FEP group versus controls) and subgroups (i.e., schizophrenia/schizophreniform, psychotic bipolar I disorder, psychotic depression, and controls) were compared. However, when the voxelwise analyses were repeated excluding subjects with comorbid substance abuse or dependence, the resulting statistical maps revealed a focal volumetric reduction in right frontal WM, corresponding to the right middle frontal gyral WM/third subcomponent of the superior longitudinal fasciculus, in subjects with schizophrenia/schizophreniform disorder (n = 40) relative to controls (n = 89). Our results suggest that schizophrenia/schizophreniform disorder is associated with right frontal WM volume decrease at an early course of the illness.
conferenceObject 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.- 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.