Adriana M. Ayres

Cognitive deficits in first-episode psychosis: A population-based study in São Paulo, Brazil

BACKGROUND Studies conducted in high-income countries have reported significant cognitive deficits in first on set schizophrenia subjects relative to asymptotic controls, and it has been suggested that the severity of such deficits could be directly related to the duration of untreated psychosis (DUP). It is relevant to conduct similar studies in developing countries, given the supposedly better outcome for schizophrenia patients living in the latter environments. METHODS We applied verbal fluency and digit span tests to an epidemiological-based series of patients with first-onset psychoses (n=179) recruited in the city of São Paulo, and compared the findings with those from non-psychotic control subjects randomly selected from the same geographical areas (n=383). RESULTS Psychosis subjects showed lower scores on the three tests relative to controls, with greatest between-group differences for the backward digit span task (p<0.0001). There were no significant differences between subjects with affective and schizophreniform psychosis. Cognitive performance indices were negatively correlated with the severity of negative symptoms, but showed no relation to DUP. CONCLUSION We found significant cognitive deficits in patients investigated early during the course of psychotic disorders in an environment that is distinct from those where the subjects investigated in previous studies have been drawn from. We found no support to the hypothesis of an association between greater cognitive deficits and a longer DUP.

Cognitive performance is related to cortical grey matter volumes in early stages of schizophrenia: A population-based study of first-episode psychosis

Background Neuropsychological deficits have been reported in association with first-episode psychosis (FEP). Reductions in grey matter (GM) volumes have been documented in FEP subjects compared to healthy controls. However, the possible inter-relationship between the findings of those two lines of research has been scarcely investigated. Objective To investigate the relationship between neuropsychological deficits and GM volume abnormalities in a population-based sample of FEP patients compared to healthy controls from the same geographical area. Methods FEP patients (n = 88) and control subjects (n = 86) were evaluated by neuropsychological assessment (Controlled Oral Word Association Test, forward and backward digit span tests) and magnetic resonance imaging using voxel-based morphometry. Results Single-group analyses showed that prefrontal and temporo-parietal GM volumes correlated significantly (p < 0.05, corrected) with cognitive performance in FEP patients. A similar pattern of direct correlations between neocortical GM volumes and cognitive impairment was seen in the schizophrenia subgroup (n = 48). In the control group, cognitive performance was directly correlated with GM volume in the right dorsal anterior cingulate cortex and inversely correlated with parahippocampal gyral volumes bilaterally. Interaction analyses with “group status” as a predictor variable showed significantly greater positive correlation within the left inferior prefrontal cortex (BA46) in the FEP group relative to controls, and significantly greater negative correlation within the left parahippocampal gyrus in the control group relative to FEP patients. Conclusion Our results indicate that cognitive deficits are directly related to brain volume abnormalities in frontal and temporo-parietal cortices in FEP subjects, most specifically in inferior portions of the dorsolateral prefrontal cortex.

Frontal and anterior cingulate activation during overt verbal fluency in patients with first episode psychosis

OBJECTIVE Functional neuroimaging studies using phonological verbal fluency tasks allow the assessment of neural circuits relevant to the neuropsychology of psychosis. There is evidence that the prefrontal cortex and anterior cingulate gyrus present different activation patterns in subjects with chronic schizophrenia relative to healthy controls. We assessed the functioning in these brain regions during phonological verbal fluency in subjects with recent-onset functional psychoses, using functional magnetic resonance imaging (FMRI). METHODS Seven patients with functional psychoses (3 schizophreniform, 4 affective) and 9 healthy controls were studied. We compared functional magnetic resonance images acquired during articulation of words beginning with letters classified as easy for word production in Portuguese. Statistical comparisons were performed using non-parametric tests. RESULTS There were no differences between patients and controls in task performance. Controls showed greater activation than patients in the left rostral anterior cingulate gyrus and right inferior prefrontal cortex, whereas patients showed stronger activation than controls in a more dorsal part of the anterior cingulate gyrus bilaterally and in a more superior portion of the right prefrontal cortex. CONCLUSION Our preliminary findings of attenuated engagement of inferior prefrontal cortex and anterior cingulate gyrus in patients with recent onset psychosis during phonological verbal fluency are consistent with those of previous studies. The greater activation found in other parts of the anterior cingulate gyrus and prefrontal cortex in patients may be related to a compensatory response that is required to maintain normal task performance, and suggests a pattern of disorganized activity of different functional anterior cingulate gyrus units in association with psychotic conditions.

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.

Phonemic Fluency in Portuguese-speaking Subjects in Brazil: Ranking of Letters

Phonological verbal fluency studies in English most commonly employ the letters F-A-S as stimuli. We assessed the production of words with these and 14 other letters in Portuguese-speaking healthy subjects (n = 74). The letters F-A-S were ranked among the easiest to produce words in one minute, which is consistent with the findings of studies with English-speaking subjects. There were differences in the overall ranking of letters depending on whether the total word number or the latency between words were considered. Our findings provide a databank of phonological verbal fluency performance using different stimuli in Portuguese, and demonstrate that the ranking of the letters F-A-S is comparable between the English and Portuguese languages in terms of the level of difficulty to produce words, when the task is used in its traditional format.

Brain activity patterns during phonological verbal fluency performance with varying levels of difficulty: A functional magnetic resonance imaging study in Portuguese-speaking healthy individuals

A large number of functional neuroimaging studies have investigated the brain circuitry which is engaged during performance of phonological verbal fluency tasks, and the vast majority of these have been carried out in English. Although there is evidence that this paradigm varies depending on the language spoken, it is unclear if this difference is associated with differences in brain activation patterns. Also, there is neuroimaging evidence that the patterns of regional cerebral activation during verbal fluency tasks may vary with the level of task demanded. In particular, the engagement of the anterior cingulate cortex seems to be relative to cognitive demand. We compared functional magnetic resonance imaging data in healthy Portuguese-speaking subjects during overt production of words beginning with letters classified as easy or hard for word production in Portuguese. Compared to the baseline condition, the two verbal fluency tasks (with either easy or hard letters) engaged a network including the left inferior and middle frontal cortices, anterior cingulate cortex, putamen, thalamus and cerebellum (p < .001). The direct comparison between the two verbal fluency conditions showed greater cerebellar activation in the easy condition relative to the hard condition. In the anterior cingulate cortex, there was a direct correlation between activity changes and verbal fluency performance during the hard condition only. Despite grammatical differences, the changes in patterns of brain activity during verbal fluency performance observed in our study are in accordance with findings of previous neuroimaging studies of verbal fluency carried out in English and other languages, with recruitment of a set of distributed cerebral areas during word production.

Cognitive functioning in subjects with recent-onset psychosis from a low-middle-income environment: Multiple-domain deficits and longitudinal evaluation

Cognitive deficits are a key feature of recent-onset psychosis, but there is no consensus on whether such deficits are generalized or confined to specific domains. Besides, it is unclear whether cognitive deficits: a) are found in psychotic patients in samples from outside high-income countries; and b) whether they progress uniformly over time in schizophrenia and affective psychoses. We applied 12 tests organized into eight cognitive domains, comparing psychosis patients (n = 56, time from initial contact = 677.95+/-183.27 days) versus healthy controls (n=70) recruited from the same area of São Paulo, Brazil. Longitudinal comparisons (digit span and verbal fluency) were conducted between a previous assessment of the subjects carried out at their psychosis onset, and the current follow-up evaluation. Psychosis patients differed significantly from controls on five domains, most prominently on verbal memory. Cognitive deficits remained detectable in separate comparisons of the schizophrenia subgroup and, to a lesser extent, the affective psychosis subjects against controls. Longitudinal comparisons indicated significant improvement in schizophrenia, affective psychoses, and control subjects, with no significant group-by-time interactions. Our results reinforce the view that there are generalized cognitive deficits in association with recent-onset psychoses, particularly of non-affective nature, which persist over time.

Volume reduction of the corpus callosum and its relationship with deficits in interhemispheric transfer of information in recent-onset psychosis

The present study aimed to investigate the presence of corpus callosum (CC) volume deficits in a population-based recent-onset psychosis (ROP) sample, and whether CC volume relates to interhemispheric communication deficits. For this purpose, we used voxel-based morphometry comparisons of magnetic resonance imaging data between ROP (n =122) and healthy control (n = 94) subjects. Subgroups (38 ROP and 39 controls) were investigated for correlations between CC volumes and performance on the Crossed Finger Localization Test (CFLT). Significant CC volume reductions in ROP subjects versus controls emerged after excluding substance misuse and non-right-handedness. CC reductions retained significance in the schizophrenia subgroup but not in affective psychoses subjects. There were significant positive correlations between CC volumes and CFLT scores in ROP subjects, specifically in subtasks involving interhemispheric communication. From these results, we can conclude that CC volume reductions are present in association with ROP. The relationship between such deficits and CFLT performance suggests that interhemispheric communication impairments are directly linked to CC abnormalities in ROP.

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