Pedro Rosa

Lack of progression of brain abnormalities in first-episode psychosis: a longitudinal magnetic resonance imaging study

BACKGROUND Some neuroimaging studies have supported the hypothesis of progressive brain changes after a first episode of psychosis. We aimed to determine whether (i) first-episode psychosis patients would exhibit more pronounced brain volumetric changes than controls over time and (ii) illness course/treatment would relate to those changes. METHOD Longitudinal regional grey matter volume and ventricle:brain ratio differences between 39 patients with first-episode psychosis (including schizophrenia and schizophreniform disorder) and 52 non-psychotic controls enrolled in a population-based case-control study. RESULTS While there was no longitudinal difference in ventricle:brain ratios between first-episode psychosis subjects and controls, patients exhibited grey matter volume changes, indicating a reversible course in the superior temporal cortex and hippocampus compared with controls. A remitting course was related to reversal of baseline temporal grey matter deficits. CONCLUSIONS Our findings do not support the hypothesis of brain changes indicating a progressive course in the initial phase of psychosis. Rather, some brain volume abnormalities may be reversible, possibly associated with a better illness course.

Cannabis use, cognition and brain structure in first-episode psychosis.

Cannabis use is highly prevalent worldwide and it is associated with psychosis, but its effects on brain structure and cognition are still controversial. The aim of this paper is to investigate cognitive functioning and brain structure in patients with their first episode of psychosis who used Cannabis. We examined gray matter and lateral ventricle volumes in 28 patients with first-episode psychosis and a history of Cannabis use, 78 patients without a history of Cannabis use and 80 healthy controls who had not used Cannabis. Cognition was assessed using forward and backwards digit span tests, from the Wechsler Memory Scale-Third Edition (WMS-III) and the Controlled Oral Word Association Test (COWAT). Patients with a history of Cannabis use had less brain abnormalities, characterized by gray matter and lateral ventricle volume preservation, as well as less attentional and executive impairments compared to patients without a history of Cannabis use. Cannabis-using patients who develop psychosis have less neurodevelopmental impairment and better cognitive reserve than other psychotic patients; perhaps reflecting different etiological processes.

Lateral ventricle differences between first-episode schizophrenia and first-episode psychotic bipolar disorder: A population-based morphometric MRI study

Abstract Objectives. The extent to which psychotic disorders fall into distinct diagnostic categories or can be regarded as lying on a single continuum is controversial. We compared lateral ventricle volumes between a large sample of patients with first-episode schizophrenia or bipolar disorder and a healthy control group from the same neighbourhood. Methods. Population-based MRI study with 88 first-episode psychosis (FEP) patients, grouped into those with schizophrenia/schizophreniform disorder (N=62), bipolar disorder (N=26) and 94 controls. Results. Right and left lateral ventricular and right temporal horn volumes were larger in FEP subjects than controls. Within the FEP sample, post-hoc tests revealed larger left lateral ventricles and larger right and left temporal horns in schizophrenia subjects relative to controls, while there was no difference between patients with bipolar disorder and controls. None of the findings was attributable to effects of antipsychotics. Conclusions. This large-sample population-based MRI study showed that neuroanatomical abnormalities in subjects with schizophrenia relative to controls from the same neighbourhood are evident at the first episode of illness, but are not detectable in bipolar disorder patients. These data are consistent with a model of psychosis in which early brain insults of neurodevelopmental origin are more relevant to schizophrenia than to bipolar disorder.

Longitudinal follow-up of cavum septum pellucidum and adhesio interthalamica alterations in first-episode psychosis: a population-based MRI study

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×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×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.

What determines continuing grey matter changes in first-episode schizophrenia and affective psychosis?

BACKGROUND Magnetic resonance imaging (MRI) studies have shown that brain abnormalities in psychosis might be progressive during the first years of illness. We sought to determine whether first-episode psychosis (FEP) subjects show progressive regional grey matter (GM) changes compared with controls, and whether those changes are associated with diagnosis, illness course or antipsychotic (AP) use. METHOD Thirty-two subjects with first-episode schizophrenia-spectrum disorders (FESZ), 24 patients with first-episode affective psychoses (FEAP) and 34 controls recruited using a population-based design underwent structural MRI scanning at baseline and at a 5-year follow-up. Regional GM volumes were assessed with voxel-based morphometry (VBM). Patients were treated at community settings, and about half of them remained mainly untreated. RESULTS No significant progressive changes in GM regional volumes were observed in either the FESZ or FEAP group overall. However, FESZ subjects with a non-remitting course showed GM decrements in the left superior temporal gyrus (STG) and insula relative to remitted FESZ subjects. Non-remitted FEAP subjects exhibited a GM decrease in the dorsolateral prefrontal cortex (DLPFC) bilaterally in comparison to remitted FEAP subjects. Among FESZ subjects, AP use was associated with regional GM decrements in the right insula and increments in the cerebellum. CONCLUSIONS Our results suggest that the progression of brain abnormalities in FEP subjects is restricted to those with a poor outcome and differs between diagnosis subgroups. AP intake is associated with a different pattern of GM reductions over time.

Corpus callosum volumes in recent-onset schizophrenia are correlated to positive symptom severity after 1 year of follow-up

Predicting the prognosis of schizophrenia is of critical importance but there are no valid biomarkers for such purpose. In case–control studies of schizophrenia using magnetic resonance imaging (MRI), the corpus callosum (CC) consistently displays alterations in morphology (Downhill et al., 2000; John et al., 2008), microstructural integrity (Mitelman et al., 2007; Whitford et al., 2010) and functioning (Chaim et al., 2010). In a previous voxel-basedmorphometry (VBM) study comparing recent-onset psychosis (ROP) patients to healthy controls, we reported CC volume reductions in schizophrenia spectrum subjects (Chaim et al, 2010). Herein, we investigated correlations between baseline CC volumes and the clinical prognosis of patients in regard to their symptom severity after 1 year. The patient samplewasdrawn fromapreviously described ROPpool (n=122) (Chaim et al., 2010).We included herein only thosewith confirmed DSM-IV schizophrenia (n=62) or schizoaffective disorder (n=07) (see demographic/clinical data in Table 1). Outcomemeasures were obtained using the Positive andNegative Syndrome Scale (PANSS) 1 year after initial identification of patients. MRI datasets were acquired

Multi-center MRI prediction models: Predicting sex and illness course in first episode psychosis patients

ABSTRACT Structural 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‐learning 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 São 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. HighlightsMulti‐center neuroimaging data can be combined to classify clear biological outcome.Classification is only significant in centers with similar illness outcome definition.Multi‐center models can increase performance of smaller and heterogeneous samples.Multi‐center studies should use large samples and standardized clinical information.Multi‐center models have the potential to yield clinically useful predictions.

Acquisition and retention of basic pathophysiological knowledge in psychiatry.

ObjectiveAn important and yet underexplored issue in medical education concerns the extent to which students retain early taught theoretical knowledge during subsequent stages of their academic schooling. This study aimed to assess the degree to which medical students retain basic pathophysiological knowledge on biological psychiatry across different stages of medical education.MethodsA cross-sectional investigation was conducted using a multiple choice questionnaire (MCQ) of objective pathophysiological knowledge taught in a course given to second-year students, supplemented by questions measuring subjective interest and attributed importance to the content taught. Comparisons (ANOVA with post hoc Tukey tests) were carried out among five groups (n = 417): baseline (freshmen), pre-intervention group (second-year students attending the first day of the course), immediate tested group (second-year students on the final day of the course), 1-year delayed tested group (third-year students), and 3-years delayed tested group (interns).ResultsIn comparison to the baseline and pre-intervention groups, the other three groups that received teaching displayed significantly better levels of knowledge (p < 0.0001). Differently, scores of interest and attributed importance were higher in the pre-intervention group relative to all other groups that were tested after having been given the course (p < 0.005). There were no significant associations between knowledge retention, attributed importance, and interest within pre-intervention or post-intervention groups.ConclusionsThe only modest loss of knowledge over time indicates that a large proportion of early taught content is retained throughout the later years of medical education. Nevertheless, retained knowledge does not seem to be associated with subjective interest and attributed importance to such early taught content.

Corrigendum to “Cannabis use, cognition and brain structure in first-episode psychosis” [Schizophr. Res., 147 (2013), 209–215]

a Laboratory of Psychiatric Neuroimaging (LIM-21), Department of Psychiatry, Faculty ofMedicine, University of Sao Paulo (USP), Rua Dr Ovidio Pires de Campos, s/n, 05403-010 Sao Paulo, SP, Brazil b Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), USP, Rua Dr Ovidio Pires de Campos, s/n, 05403-010 Sao Paulo, SP, Brazil c Interdisciplinary Group of Studies on Alcohol and Drugs (GREA) and Equilibrium Program, Department of Psychiatry, Faculty of Medicine, USP, Rua Dr Ovidio Pires de Campos, s/n, 05403-010 Sao Paulo, SP, Brazil d LIM-23, Institute of Psychiatry, Clinics Hospital, Faculty of Medicine, USP, Rua Dr Ovidio Pires de Campos, s/n, 05403-010 Sao Paulo, SP, Brazil e Department of Preventive Medicine, Faculty of Medicine, USP, Av. Dr. Arnaldo, 455, 2° andar, Cerqueira Cesar, 01246-903 Sao Paulo, SP, Brazil f CEAPPesq, Institute of Mathematic and Statistics (IME), Department of Psychiatry, USP, Rua do Matao, 1010 — Cidade Universitaria, 05508-090 Sao Paulo, SP, Brazil g Department of Psychosis Studies, Institute of Psychiatry, Kings College, De Crespigny Park, London SE5 8AF, UK h Department of Neuroscience and Behaviour, Faculty of Medicine, USP, Av. Bandeirantes, 3900, Monte Alegre, 14048-900 Ribeirao Preto, SP, Brazil

Deep Learning for Quality Control of Subcortical Brain 3D Shape Models

We present several deep learning models for assessing the morphometric fidelity of deep grey matter region models extracted from brain MRI. We test three different convolutional neural net architectures (VGGNet, ResNet and Inception) over 2D maps of geometric features. Further, we present a novel geometry feature augmentation technique based on parametric spherical mapping. Finally, we present an approach for model decision visualization, allowing human raters to see the areas of subcortical shapes most likely to be deemed of failing quality by the machine. Our training data is comprised of 5200 subjects from the ENIGMA Schizophrenia MRI cohorts, and our test dataset contains 1500 subjects from the ENIGMA Major Depressive Disorder cohorts. Our final models reduce human rater time by 46-70%. ResNet outperforms VGGNet and Inception for all of our predictive tasks.