RESUMEN
OBJECTIVE: To investigate the influence of brain-derived neurotrophic factor (BDNF) gene variations on cognitive performance and clinical symptomatology in first-episode psychosis (FEP). METHODS: We performed BDNF val66met variant genotyping, cognitive testing (verbal fluency and digit spans) and assessments of symptom severity (as assessed with the PANSS) in a population-based sample of FEP patients (77 with schizophreniform psychosis and 53 with affective psychoses) and 191 neighboring healthy controls. RESULTS: There was no difference in the proportion of Met allele carriers between FEP patients and controls, and no significant influence of BDNF genotype on cognitive test scores in either of the psychosis groups. A decreased severity of negative symptoms was found in FEP subjects that carried a Met allele, and this finding reached significance for the subgroup with affective psychoses (p < 0.01, ANOVA). CONCLUSIONS: These results suggest that, in FEP, the BDNF gene Val66Met polymorphism does not exert a pervasive influence on cognitive functioning but may modulate the severity of negative symptoms.
OBJETIVO: Investigar a influência da variação do gene do fator neurotrófico derivado do cérebro (BDNF) no desempenho cognitivo e na sintomatologia clínica durante o primeiro episódio psicótico (PEP). MÉTODOS: Foram realizados a genotipificação das variantes Val66met do BDNF, o teste cognitivo (fluência verbal e repetição de dígitos) e as avaliações da gravidade dos sintomas (conforme avaliado pela Positive and Negative Syndrome Scale [PANSS]) em uma amostra de pacientes com PEP de base populacional (77 com psicose esquizofreniforme e 53 com psicose afetiva) e 191 vizinhos controle saudáveis. RESULTADOS: Não houve diferença na proporção de portadores do alelo Met entre pacientes com PEP e o grupo controle. Não houve influência significativa do genótipo do BDNF sobre a pontuação de cada um dos grupos psicóticos. Foi encontrada uma diminuição da gravidade dos sintomas negativos em sujeitos com PEP portadores do alelo Met, e essa descoberta mostrou-se significativa para o subgrupo com psicose afetiva (p < 0,01, ANOVA). CONCLUSÕES: Os resultados sugerem que, no PEP, o polimorfismo Val66Met do gene do BDNF não exerce uma influência importante sobre o funcionamento cognitivo, mas pode modular a gravidade dos sintomas negativos.
Asunto(s)
Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Factor Neurotrófico Derivado del Encéfalo/genética , Cognición/fisiología , Polimorfismo de Nucleótido Simple/genética , Trastornos Psicóticos/genética , Brasil , Genotipo , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: To investigate the influence of brain-derived neurotrophic factor (BDNF) gene variations on cognitive performance and clinical symptomatology in first-episode psychosis (FEP). METHODS: We performed BDNF val66met variant genotyping, cognitive testing (verbal fluency and digit spans) and assessments of symptom severity (as assessed with the PANSS) in a population-based sample of FEP patients (77 with schizophreniform psychosis and 53 with affective psychoses) and 191 neighboring healthy controls. RESULTS: There was no difference in the proportion of Met allele carriers between FEP patients and controls, and no significant influence of BDNF genotype on cognitive test scores in either of the psychosis groups. A decreased severity of negative symptoms was found in FEP subjects that carried a Met allele, and this finding reached significance for the subgroup with affective psychoses (p < 0.01, ANOVA). CONCLUSIONS: These results suggest that, in FEP, the BDNF gene Val66Met polymorphism does not exert a pervasive influence on cognitive functioning but may modulate the severity of negative symptoms.
Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/genética , Cognición/fisiología , Polimorfismo de Nucleótido Simple/genética , Trastornos Psicóticos/genética , Adolescente , Adulto , Brasil , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
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.
Asunto(s)
Mapeo Encefálico , Encéfalo/irrigación sanguínea , Encéfalo/fisiología , Fonética , Conducta Verbal/fisiología , Adulto , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Oxígeno/sangre , Estimulación Luminosa , Portugal , Psicolingüística , Estadística como Asunto , Vocabulario , Adulto JovenRESUMEN
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.
Asunto(s)
Trastornos del Conocimiento/etiología , Cuerpo Calloso/patología , Lateralidad Funcional/fisiología , Trastornos Psicóticos/complicaciones , Trastornos Psicóticos/patología , Transferencia de Experiencia en Psicología/fisiología , Adolescente , Adulto , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Estadística como Asunto , Adulto JovenRESUMEN
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.
Asunto(s)
Corteza Cerebral/patología , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/patología , Esquizofrenia/complicaciones , Esquizofrenia/patología , Adulto , Mapeo Encefálico , Corteza Cerebral/fisiopatología , Planificación en Salud Comunitaria/métodos , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Pruebas Neuropsicológicas , Análisis de Componente Principal , Estadística como Asunto , Adulto JovenRESUMEN
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.
Asunto(s)
Trastornos del Conocimiento/epidemiología , Países en Desarrollo , Trastornos Psicóticos/epidemiología , Esquizofrenia/epidemiología , Psicología del Esquizofrénico , Población Urbana/estadística & datos numéricos , Adulto , Brasil , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/psicología , Comorbilidad , Estudios Transversales , Depresión/diagnóstico , Depresión/epidemiología , Depresión/psicología , Femenino , Humanos , Masculino , Memoria a Corto Plazo , Persona de Mediana Edad , Pruebas Neuropsicológicas/estadística & datos numéricos , Psicometría/estadística & datos numéricos , Trastornos Psicóticos/diagnóstico , Trastornos Psicóticos/psicología , Esquizofrenia/diagnóstico , Estadística como Asunto , Conducta VerbalRESUMEN
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.
Asunto(s)
Lóbulo Frontal/fisiopatología , Trastornos Psicóticos/fisiopatología , Conducta Verbal/fisiología , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Corteza Prefrontal/fisiopatología , Trastornos Psicóticos/diagnósticoRESUMEN
OBJETIVO: Estudos de neuroimagem funcional empregando tarefa de fluência verbal fonológica têm permitido a avaliacão dos circuitos neurais relevantes à neuropsicologia das psicoses. Pacientes com esquizofrenia crônica apresentam diferenca nos padrões de ativacão em córtex pré-frontal e giro do cíngulo anterior em relacão a controles normais. Essas regiões cerebrais foram avaliadas por ressonância magnética funcional, durante tarefa de fluência verbal fonológica, em pacientes com psicose funcional de início recente. MÉTODOS: Sete pacientes com psicose funcional (3 esquizofreniformes, 4 afetivos) e nove controles saudáveis foram estudados. Foram comparadas as imagens de ressonância magnética funcional adquiridas durante a articulacão de palavras que comecassem com letras classificadas como "fáceis" para a producão de palavras em Português. Comparacões estatísticas foram obtidas com métodos não-paramétricos. RESULTADOS: Os grupos não diferiram em relacão ao desempenho da tarefa. Os controles apresentaram maior ativacão em cíngulo anterior rostral esquerdo e em córtex pré-frontal inferior direito, enquanto os pacientes mostraram maior ativacão em uma região mais dorsal do cíngulo anterior bilateralmente e em uma porcão mais superior do córtex pré-frontal direito. CONCLUSAO: Nossos resultados preliminares são consistentes com estudos prévios e demonstram menor ativacão em córtex pré-frontal e cíngulo anterior em pacientes com psicose de início recente durante tarefa de fluência verbal fonológica. A maior ativacão em outras partes do cíngulo anterior e do córtex pré-frontal em pacientes pode estar relacionada a uma resposta compensatória necessária para a manutencão do desempenho normal da tarefa e sugere que uma alteracão do padrão de atividade das diversas unidades funcionais do cíngulo anterior está associada aos transtornos psicóticos.