Nicotinic Acetylcholine Receptor Dysfunction in Addiction and in Some Neurodegenerative and Neuropsychiatric Diseases.

The cholinergic system plays an essential role in brain development, physiology, and pathophysiology. Herein, we review how specific alterations in this system, through genetic mutations or abnormal receptor function, can lead to aberrant neural circuitry that triggers disease. The review focuses on the nicotinic acetylcholine receptor (nAChR) and its role in addiction and in neurodegenerative and neuropsychiatric diseases and epilepsy. Cholinergic dysfunction is associated with inflammatory processes mainly through the involvement of α7 nAChRs expressed in brain and in peripheral immune cells. Evidence suggests that these neuroinflammatory processes trigger and aggravate pathological states. We discuss the preclinical evidence demonstrating the therapeutic potential of nAChR ligands in Alzheimer disease, Parkinson disease, schizophrenia spectrum disorders, and in autosomal dominant sleep-related hypermotor epilepsy. PubMed and Google Scholar bibliographic databases were searched with the keywords indicated below.

Guía práctica para el uso de clozapina en niños/as y adolescentes / Practical guidelines for the use of clozapine in children and adolescents

El uso de clozapina (CZP) en niños/as y adolescentes ha estado históricamente limitado, debido a los efectos adversos y riesgos médicos asociados al fármaco, a pesar de ser una herramienta farmacológica de gran efectividad en la psiquiatría general. A continuación, se presenta una guía clínica con los siguientes objetivos: 1) identificar los criterios de indicación de CZP en niños, niñas y adolescentes (NNA) según la evidencia disponible; 2) entregar algunas directrices a los clínicos y profesionales de salud respecto a la prescripción de CZP y precauciones a tener en consideración en esta población y; 3) entregar algunos datos comparativos del uso de CZP entre población infantojuvenil y población adulta. Todo lo anterior tiene como finalidad poder entregar la información necesaria para que los clínicos no limiten el uso de este fármaco y puedan prescribirlo de acuerdo con la evidencia científica disponible.

The use of clozapine (CZP) in children and adolescents has historically been limited due to the adverse effects and medical risks commonly associated with the drug, despite being a highly effective pharmacological tool in general psychiatry. Below we developed a clinical guideline with the following objectives: 1) identify the indication criteria for CZP in children and adolescents (NNA) according to the available evidence; 2) provide some guidelines to clinicians and health professionals regarding the prescription of CZP and precautions to be taken into account in this population and; 3) provide some comparative data on the use of CZP between the pediatric and adult population. The purpose of the guideline is to provide the necessary information so that clinicians do not limit the use of CLZ when needed and can prescribe it safely and according to the available scientific evidence.

Alteraciones neurocognitivas en la esquizofrenia. Análisis factorial / Neurocognitive alterations in schizophrenia. Factor analysis / Alterações neurocognitivas na esquizofrenia. Análise fatorial

Objetivo: el déficit en los procesos cognitivos, específicamente en el rendimiento ejecutivo, de los pacientes con esquizofrenia se ha asociado con mala adaptación social. Un modelo factorial de las funciones ejecutivas permitiría detectar la asociación entre el perfil sintomático, el deterioro de la función ejecutiva y las necesidades de rehabilitación. El objetivo de esta investigación fue identificar factores de la función ejecutiva mediante un análisis factorial de las puntuaciones tipificadas de una serie de pruebas neuropsicológicas, en un grupo de pacientes ambulatorios con diagnósticos del espectro de la esquizofrenia. Metodología: estudio factorial mediante un análisis de componentes principales (ACP) con rotación ortogonal (varimax) de 13 medidas neuropsicológicas estandarizadas. Resultados: se obtuvieron tres factores independientes: (1) flexibilidad cognitiva, (2) control de la interferencia y memoria de trabajo y (3) velocidad de procesamiento y atención, que proporcionan una medición psicométrica adecuada del desempeño ejecutivo de los pacientes estudiados. Conclusiones: el análisis revela una estructura compleja de tres dimensiones cognitivas discretas que se pueden medir con una batería de uso común en la clínica.

Objective: The deficit in cognitive processes, specifically in executive function of patients with schizophrenia, has been associated with poor social adaptation. A factor model of executive functions would allow for the detection of the association between the symptomatic profile, the deterioration of the executive function, and rehabilitation needs. The objective of this study was to identify factors of the executive function through factor analysis of typified scores from a series of neuropsychological tests in a group of outpatients diagnosed with schizophrenia. Methodology: Factor study through principal components analysis (PCA) with orthogonal rotation (varimax) of 13 standardized neuropsychological measures. Results: Three independent factors were obtained: (1) cognitive flexibility, (2) interference control and working memory, and (3) processing speed and attention, which provide an adequate psychometric measurement of executive function in the patients studied. Conclusions: The analysis reveals a complex structure of three discrete cognitive dimensions that can be measured with cognitive assessment tools commonly used in the hospital.

Objetivo: o déficit nos processos cognitivos, especificamente no rendimento executivo, dos pacientes com esquizofrenia se há associado com má adaptação social. Um modelo fatorial das funções executivas permitiria detectar a associação entre o perfil sintomático, o deterioro da função executiva e as necessidades de reabilitação. O objetivo desta investigação foi identificar fatores da função executiva mediante um análise fatorial das pontuações tipificadas de uma série de provas neuropsicológicas, num grupo de pacientes ambulatórios com diagnósticos do espectro da esquizofrenia. Metodologia: estudo fatorial mediante uma análise de componentes principais (ACP) com rotação ortogonal (varimax) de 13 medidas neuropsicológicas padronizadas. Resultados: se obtiveram três fatores independentes: (1) flexibilidade cognitiva, (2) controle da interferência e memória de trabalho e (3) velocidade de processamento e atenção, que proporcionam uma medição psicométrica adequada do desempenho executivo dos pacientes estudados. Conclusões: a análise revela uma estrutura complexa de três dimensões cognitivas discretas que se podem medir com uma bateria de uso comum na clínica.