Cognición y síntomas negativos en la esquizofrenia

Aunque los delirios y alucinaciones, también denominados síntomas positivos, se han considerado como los más característicos de la esquizofrenia y tradicionalmente han supuesto la diana de los tratamientos para el trastorno, hoy en día se conoce que no son éstos los síntomas más ligados al pronóstico y funcionalidad de los pacientes. En los últimos años se ha puesto de manifiesto que los denominados síntomas negativos (que incluyen aspectos como la abulia, la asociabilidad, la anhedonia, la alogia o el aplanamiento afectivo) y la disfunción cognitiva (que afecta de manera generalizada al rendimiento cognitivo de los pacientes) están mucho más estrechamente ligados a la funcionalidad de las personas con esquizofrenia que los síntomas positivos, y tienen implicaciones pronósticas muy importantes. Los síntomas negativos y cognitivos presentan algunos aspectos similares, como su cualidad nuclear en la esquizofrenia, su presencia desde el inicio del trastorno e incluso antes de la aparición de los síntomas positivos, su independencia de estos síntomas positivos, su persistencia temporal, su escasa respuesta a los tratamientos antipsicóticos actuales, o su estrecha relación con el funcionamiento y el pronóstico de los pacientes. La relación entre cognición y síntomas negativos ha sido estudiada por diferentes autores. Aunque en general se ha descrito una asociación débil, la literatura muestra hallazgos contradictorios. En este sentido, se ha destacado la relevancia de diversos factores, en especial de tipo metodológico, a la hora de estudiar la relación entre estas dos dimensiones clínicas de la esquizofrenia. Así pues, dada la trascendencia pronóstica de la cognición y los síntomas negativos en la esquizofrenia, y los hallazgos contradictorios descritos en la literatura acerca de su asociación, la presente tesis se propuso estudiar la relación entre ambos tipos de síntomas y los factores que influyen en la misma..

Cognition and the five-factor model of the Positive and Negative Syndrome Scale in schizophrenia

Different exploratory and confirmatory factorial analyses of the Positive and Negative Syndrome Scale (PANSS) have found a number of factors other than the original positive, negative, and general psychopathology. Based on a review of previous studies and using confirmatory factor analyses (CFA), Wallwork et al. (Schizophr Res 2012; 137: 246–250) have recently proposed a consensus five-factor structure of the PANSS. This solution includes a cognitive factor which could be a useful measure of cognition in schizophrenia. Our objectives were 1) to study the psychometric properties (factorial structure and reliability) of this consensus five-factor model of the PANSS, and 2) to study the relationship between executive performance assessed using the Wisconsin Card Sorting Test (WCST) and the proposed PANSS consensus cognitive factor (composed by items P2-N5-G11). This cross-sectional study included a final sample of 201 Spanish outpatients diagnosed with schizophrenia. For our first objective, CFA was performed and Cronbach's alphas of the five factors were calculated; for the second objective, sequential linear regression analyses were used. The results of the CFA showed acceptable fit indices (NNFI = 0.94, CFI = 0.95, RMSEA = 0.08). Cronbach's alphas of the five factors were adequate. Regression analyses showed that this five-factor model of the PANSS explained more of the WCST variance than the classical three-factor model. Moreover, higher cognitive factor scores were associated with worse WCST performance. These results supporting its factorial structure and reliability provide robustness to this consensus PANSS five-factor model, and indicate some usefulness of the cognitive factor in the clinical assessment of schizophrenic patients

Reduced visual surround suppression in schizophrenia shown by measuring contrast detection thresholds.

Visual perception in schizophrenia is attracting a broad interest given the deep knowledge that we have about the visual system in healthy populations. One example is the class of effects known collectively as visual surround suppression. For example, the visibility of a grating located in the visual periphery is impaired by the presence of a surrounding grating of the same spatial frequency and orientation. Previous studies have suggested abnormal visual surround suppression in patients with schizophrenia. Given that schizophrenia patients have cortical alterations including hypofunction of NMDA receptors and reduced concentration of GABA neurotransmitter, which affect lateral inhibitory connections, then they should be relatively better than controls at detecting visual stimuli that are usually suppressed. We tested this hypothesis by measuring contrast detection thresholds using a new stimulus configuration. We tested two groups: 21 schizophrenia patients and 24 healthy subjects. Thresholds were obtained using Bayesian staircases in a four-alternative forced-choice detection task where the target was a grating within a 3∘ Butterworth window that appeared in one of four possible positions at 5∘ eccentricity. We compared three conditions, (a) target with no-surround, (b) target embedded within a surrounding grating of 20∘ diameter and 25% contrast with same spatial frequency and orthogonal orientation, and (c) target embedded within a surrounding grating with parallel (same) orientation. Previous results with healthy populations have shown that contrast thresholds are lower for orthogonal and no-surround (NS) conditions than for parallel surround (PS). The log-ratios between parallel and NS thresholds are used as an index quantifying visual surround suppression. Patients performed poorly compared to controls in the NS and orthogonal-surround conditions. However, they performed as well as controls when the surround was parallel, resulting in significantly lower suppression indices in patients. To examine whether the difference in suppression was driven by the lower NS thresholds for controls, we examined a matched subgroup of controls and patients, selected to have similar thresholds in the NS condition. Patients performed significantly better in the PS condition than controls. This analysis therefore indicates that a PS raised contrast thresholds less in patients than in controls. Our results support the hypothesis that inhibitory connections in early visual cortex are impaired in schizophrenia patients

Differential dorsolateral prefrontal cortex activation during a verbal n-back task according to sensory modality

Functional neuroimaging studies carried out on healthy volunteers while performing different n-back tasks have shown a common pattern of bilateral frontoparietal activation, especially of the dorsolateral prefrontal cortex (DLPFC). Our objective was to use functional magnetic resonance imaging (fMRI) to compare the pattern of brain activation while performing two similar n-back tasks which differed in their presentation modality. Thirteen healthy volunteers completed a verbal 2-back task presenting auditory stimuli, and a similar 2-back task presenting visual stimuli. A conjunction analysis showed bilateral activation of frontoparietal areas including the DLPFC. The left DLPFC and the superior temporal gyrus showed a greater activation in the auditory than in the visual condition, whereas posterior brain regions and the anterior cingulate showed a greater activation during the visual than during the auditory task. Thus, brain areas involved in the visual and auditory versions of the n-back task showed an important overlap between them, reflecting the supramodal characteristics of working memory. However, the differences found between the two modalities should be considered in order to select the most appropriate task for future clinical studies. © 2009 Elsevier B.V. All rights reserved