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2016, Número 1

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Salud Mental 2016; 39 (1)


Neurobiología de la depresión mayor y de su tratamiento farmacológico

Cruzblanca HH, Lupercio CP, Collas AJ, Castro RE

Idioma: Español
Referencias bibliográficas: 116
Paginas: 47-58
Archivo PDF: 725.12 Kb.


RESUMEN

Introducción La depresión mayor (DM) se debe a la interacción de factores ambientales, genéticos y epigenéticos, que atenúan la transmisión monoaminérgica en el cerebro. Sin embargo, poco se conoce sobre los mecanismos fisiopatológicos que subyacen a ella.
Objetivo Proponer una visión integral sobre la fisiopatología de la DM y los mecanismos de acción de los fármacos antidepresivos.
Método Se empleó la base PubMed para la búsqueda bibliográfica. La mayoría son investigaciones experimentales y estudios de genética molecular o de imágenes cerebrales en humanos.
Resultados La DM se asocia con: i) menor volumen de la corteza cingulada anterior; ii) hiper-metabolismo del área Cg25; iii) menor expresión del receptor 5-HT1A; iv) mayor expresión de la monoamino oxidasa A. Algunos polimorfismos están asociados a la fisiopatología. El estrés crónico reduce la expresión del 5-HT1A. Los antidepresivos atenúan el hiper-metabolismo del área Cg25, estimulan la neurogénesis y activan la vía del AMPc. Encontramos que la imipramina aumenta y reduce la expresión de Gαs y Gαz, respectivamente (datos sin publicar).
Discusión y conclusión El déficit en la transmisión monoaminérgica puede deberse a: i) el polimorfismo G1463A en el gen de la enzima hTPH2 que reduce la síntesis de serotonina; ii) el polimorfismo C(-1019)G en el gen del receptor 5-HT1A, aumentando su transcripción en el rafé e implicando menor liberación del neurotransmisor; iii) mayor degradación de las monoaminas. La menor expresión del receptor 5-HT1A se discute considerando su acción inhibitoria en la corteza prefrontal. Los cambios en la expresión de Gαs y Gαz coinciden con la estimulación de la vía del AMPc.


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