El circuito cerebral de la recompensa en los trastornos afectivos / Brain Reward Circuitry in Affective Disorders

Los síntomas conductuales de la depresión son numerosos y variados, cubriendo los dominios emocionales, motivacionales, cognitivos y fisiológicos. Estudios recientes en modelos animales de depresión y en pacientes depresivos utilizando técnicas neuropsicológicas combinadas con imagenología funcional muestran que grandes subgrupos de estos pacientes presentan deficiencias en el procesamiento de las recompensas a los estímulos emocionales positivos, que son nucleares en depresión. La proteína Rac 1, un regulador crítico de la actina del citoesqueleto, se reduce en el NAcc tanto en depresión como en modelos animales de adicción, lo que lleva al crecimiento de espinas dendríticas inmaduras en las MSNs del NAcc y esto es consecuencia de modificaciones epigenéticas selectivas en esta región, del gen que codifica Rac 1, tanto en modelos de estrés en roedores como en humanos depresivos (estudios post-mortem). El gran desarrollo de algunos de los modelos experimentales de depresión que cuentan con evidencias moleculares, sistémicas y conductuales no se han traducido en nuevos medicamentos pero al avanzar en la comprensión patofisiológica del trastorno y sus correlatos neuroimagenológicos, permitirán, junto a las modernas técnicas de investigación, buscar marcadores biológicos de los endofenotipos diferentes que se combinan para generar un trastorno que posee múltiples subtipos que los agrupan en clusters diferentes

The behavioral symptoms of depression are numerous and varied, and encompass the emotional, motivational and physiologic domains. Recent studies in animal models of depression and depressive patients, which used neuropsychological techniques combined with functional imaging, show that large subgroups of these patients display deficiencies in the processing of rewards to positive emotional stimuli, which are nuclear in depression. Rac 1 protein, a critical regulator of cytoskeleton actin, is reduced in the NAcc, both in depression as well as in animal models of addiction, which leads to the growth of immature dendritic spines in the MSNs of the NAcc, and this is the result of selective epigenetic alterations in this region, of the gene that codifies Rac1, both in models of stress in rodents as well as in depressive human beings (post-mortem studies). The great development of some of the experimental models of depression that provide molecular, systemic and behavioral evidences have not translated into new medications, but the progressive pathophysiological understanding of the disorder and its neuroimaging correlates will enable, together with the modern investigations techniques, to search for biological markers of the different endophenotypes that combine to generate a disorder which has multiple subtypes that gather in different clusters

Da herança à localização cerebral: sobre o determinismo biológico de condutas indesejadas / From heritage to cerebral localization: on the biological determinism of undesired conducts

Analisamos os argumentos utilizados, em dois momentos diferentes do século XX, para justificar o recurso a explicações biológicas de condutas consideradas como socialmente indesejadas. Referimo-nos, inicialmente, aos estudos realizados pelos higienistas de início do século, cujas explicações estavam centradas no caráter orgânico e inato dos desvios, para continuar logo com os recentes estudos da neurociência que se propõem a localizar as condutas nas sinapses inadequadas e nas explicações referidas a deficiências químicas do cérebro.

The article analyzes the arguments used in two distinct moments of the 20th century, to justify the use of biological explanations for conducts considered as socially undesirable. Firstly we refer to studies of hygienists in the early century, whose explanation were centered on the organic and innate character of deviations, then we analyze the recent studies in the neurosciences which try to locate these conducts in inadequate synapses and in explanations related to chemical cerebral deficiencies.