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Compartido neuropatología molecular a través de los principales trastornos psiquiátricos paralelos superposición

Michael J Gandal, Jillian R Haney, Neelroop N Parikshak

Science (New York, N.Y.)

|February 14, 2018

Resumen

Los factores genéticos contribuyen a los trastornos neuropsiquiátricos como el autismo y la esquizofrenia. Los patrones de expresión génica revelan cambios moleculares compartidos y distintos, que vinculan la superposición genética con la disfunción cerebral.

Área de la Ciencia:

La neurociencia
La genética
La psiquiatría

Sus antecedentes:

Las enfermedades neuropsiquiátricas tienen una base genética compleja, pero el vínculo entre las variantes genéticas y la disfunción cerebral no se comprende bien.
Comprender los fundamentos moleculares de estos trastornos es crucial para desarrollar tratamientos efectivos.

Objetivo del estudio:

Investigar las perturbaciones de la expresión génica en el cerebro en cinco trastornos psiquiátricos principales: autismo, esquizofrenia, trastorno bipolar, depresión y alcoholismo.
Identificar fenotipos moleculares compartidos y distintos y su relación con la superposición genética entre estas condiciones.

Principales métodos:

Utilizado el perfil transcriptómico para evaluar cuantitativamente los fenotipos basados en el cerebro molecular.
Se compararon patrones de expresión génica en pacientes con cinco trastornos psiquiátricos mayores con grupos de control emparejados.
Analizó la correlación entre la desregulación transcripcional compartida y la superposición poligénica (basada en el polimorfismo de un solo nucleótido) en los trastornos.

Principales resultados:

Se identificaron patrones significativos de perturbaciones de la expresión génica compartidas y distintas en los trastornos psiquiátricos estudiados.
Se demostró una relación entre el grado de desregulación transcripcional compartida y la superposición poligénica entre los trastornos.
Destacó un componente genético causal sustancial que influye en estos cambios moleculares.

Conclusiones:

El estudio proporciona una visión a nivel de sistemas de la arquitectura neurobiológica de las principales enfermedades neuropsiquiátricas.
Reveló vías de convergencia molecular y especificidad subyacentes a estos trastornos complejos.
Sugiere que los factores genéticos juegan un papel importante en la configuración del paisaje molecular de la enfermedad neuropsiquiátrica.

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