RESUMEN
BACKGROUND: Resistance to antipsychotic treatment affects up to 30% of patients with schizophrenia. Although the time course of development of treatment-resistant schizophrenia (TRS) varies from patient to patient, the reasons for these variations remain unknown. Growing evidence suggests brain dysconnectivity as a significant feature of schizophrenia. In this study, we compared fractional anisotropy (FA) of brain white matter between TRS and non-treatment-resistant schizophrenia (non-TRS) patients. Our central hypothesis was that TRS is associated with reduced FA values. METHODS: TRS was defined as the persistence of moderate to severe symptoms after adequate treatment with at least two antipsychotics from different classes. Diffusion-tensor brain MRI obtained images from 34 TRS participants and 51 non-TRS. Whole-brain analysis of FA and axial, radial, and mean diffusivity were performed using Tract-Based Spatial Statistics (TBSS) and FMRIB's Software Library (FSL), yielding a contrast between TRS and non-TRS patients, corrected for multiple comparisons using family-wise error (FWE) < 0.05. RESULTS: We found a significant reduction in FA in the splenium of corpus callosum (CC) in TRS when compared to non-TRS. The antipsychotic dose did not relate to the splenium CC. CONCLUSION: Our results suggest that the focal abnormality of CC may be a potential biomarker of TRS.
Asunto(s)
Cuerpo Calloso/diagnóstico por imagen , Esquizofrenia Resistente al Tratamiento/diagnóstico por imagen , Adulto , Imagen de Difusión Tensora , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
PURPOSE: To evaluate if the duration of epilepsy influences MRI volumes of the hippocampus, amygdala, parahippocampal gyrus, entorhinal cortex and temporal pole of both hemispheres and epileptogenic hippocampus neuronal cell density and dentate gyrus granular cells distribution in patients with refractory mesial temporal lobe epilepsy due to hippocampal sclerosis (MTLE/HS). METHODS: Seventy-seven patients with refractory MTLE/HS submitted to surgery were included. Histopathological analysis included: (1) quantitative: hippocampal subfields and total estimated hippocampal cell density (HCD), thickness of the dentate gyrus - normal, thinning or dispersion; (2) qualitative: type of HS and granule cells pathology in the dentate gyrus (normal, neuronal cell loss, dispersion and bilamination). Automated MRI-derived measurements from bilateral temporal structures (hippocampus, amygdala, parahippocampal gyrus, temporal pole, entorhinal cortex) were obtained for 58 subjects. Histopathological and imaging findings were compared with data from specimens obtained in autopsies of age-matched individuals and living controls, respectively, and the data were adjusted for the age at epilepsy onset and the frequency of focal impaired awareness seizures/month. RESULTS: Forty-two (54.5%) patients presented right HS. The greater the duration of epilepsy, the smaller the total estimated HCD (p = 0.025; r = -0.259). Patients with a normal distribution of the granular cells had a shorter epilepsy duration than those with dispersion (p = 0.018) or thinning (p = 0.031). A reduced ipsilateral hippocampal volume (r = -0.551, p = 0.017) and a smaller hippocampal asymmetry index (r = -0.414, p = 0.002) were correlated to a longer epilepsy duration. The estimated HCD was correlated to the volume of the ipsilateral hippocampus (r = 0.420, p = 0.001). CONCLUSION: Our study showed an increasing atrophy of the ipsilateral hippocampus in patients with a longer epilepsy duration. Our data suggest that this reduction in hippocampal volume is related to neuronal loss. Besides that, we also showed an increased probability of exhibiting an abnormal distribution of the granular cells in the dentate gyrus in patients with longer epilepsy duration.
Asunto(s)
Mapeo Encefálico , Encéfalo/patología , Epilepsia del Lóbulo Temporal/patología , Hipocampo/patología , Neuronas/metabolismo , Adolescente , Adulto , Anciano , Encéfalo/diagnóstico por imagen , Recuento de Células , Epilepsia del Lóbulo Temporal/complicaciones , Femenino , Hipocampo/diagnóstico por imagen , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neuronas/patología , Fosfopiruvato Hidratasa/metabolismo , Esclerosis/diagnóstico por imagen , Esclerosis/patología , Adulto JovenRESUMEN
OBJECTIVE: Several studies have shown cortical volume loss in frontotemporal regions in schizophrenia patients, and it is known that these reductions may be associated with disease symptoms and cognitive deficits. The aim of this study was to investigate possible cortical thickness correlations in frontotemporal regions in relation to age at onset and duration of illness. METHODS: One hundred forty-eight schizophrenia patients (97 males; age and SD 36.30 ± 10.06) and 87 (57 males; age and SD 36.48 ± 10.10) age-matched healthy subjects underwent a brain MRI scan. Cortical segmentation and surface statistical analysis were performed using the FreeSurfer software package. Results were corrected for multiple comparisons using the Monte Carlo method considering a cluster-corrected Type I Error of 5%. RESULTS: Compared to controls, schizophrenia patients presented significant cortical thinning in the frontotemporal, parietal, and occipital cortices. No correlation between prefrontal cortex thickness and duration of illness in patients with schizophrenia or between frontotemporal cortical thickness and age at onset was found. However, a significant interaction between age and diagnosis was observed on frontal cortical thickness with patients presenting a thinner cortex than expected for age. CONCLUSION: Although there was no correlation between age of onset and duration of illness with brain volume, our findings suggest that there is an accelerated cortical loss in schizophrenia, thus reinforcing the progressive processes of the disease.