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Nouvel éclairage de la génétique sur la psychiatrie (Dr Irène Drogou, Le quotidien du Médecin)

Les chevauchements génétiques entre les troubles psychiatriques créent la surprise. Une étude américaine dans 5 grandes pathologies psychiatriques, à savoir l’autisme, la schizophrénie, les troubles bipolaires, la dépression et l’alcoolisme, révèle dans « Science » des profils d’expression génétique qui font repenser la psychiatrie et les thérapeutiques.

Les profils d’expression génétique qui se dégagent sont partagés entre certaines maladies psychiatriques, mais parfois de façon contre-intuitive, révèle une équipe californienne en collaboration avec de grands consortiums de recherche (Common Mind, PsychENCODE, iPSYCH-BROAD). Certaines maladies psychiatriques se ressemblent davantage sur le plan biologique que ne le laisserait penser la clinique. Les troubles bipolaires par exemple se recoupent le plus au plan génétique avec la schizophrénie, davantage qu’avec la dépression.

Troubles bipolaires et schizophrénie, une proximité étonnante

« La prédisposition génétique aux troubles neuropsychiatriques implique une architecture génétique complexe, polygénique et pléiotropique », rappellent les auteurs. Alors que les facteurs de risque environnementaux et épigénétiques peuvent interférer avec l’expression des gènes, les chercheurs ont choisi de mesurer les transcriptomes, c’est-à-dire l’ensemble des ARN présents dans les cellules cérébrales, ce qui permet une mesure quantitative du phénotype.

Pour ce travail, les chercheurs ont analysé les prélèvements cérébraux post mortem chez 700 sujets : autisme (n = 50), schizophrénie (n = 159), troubles bipolaires (n = 94), dépression (n = 87) et alcoolisme (n = 17) et témoins (n = 293).

Dans l’étude, les chercheurs ont ainsi constaté un chevauchement entre l’autisme, la schizophrénie et les troubles bipolaires, avec en particulier une suractivité des gènes liés aux astrocytes. De la même façon, les scientifiques ont mis en évidence un chevauchement entre la schizophrénie, les troubles bipolaires et la dépression. Dans l’alcoolisme, les chercheurs n’ont rapporté aucune corrélation avec les 4 autres maladies psychiatriques.

De nouvelles pistes dans l’autisme

Dans l’autisme, l’étude apporte plusieurs éléments nouveaux de compréhension de la maladie, notamment avec le rôle d’une surexpression de gènes dans les symptômes autistiques. De plus, une signature très particulière a été identifiée, suggérant une surexpression de gènes de la microglie. Cette découverte pourrait être le reflet du rôle de ces cellules dans la régulation de la connectivité neuronale pendant le développement.

A contrario, des gènes d’allumage neuronal étaient éteints dans l’autisme, comme dans les troubles bipolaires et la schizophrénie. Cela suggère la responsabilité de perturbations dans la communication cellulaire cérébrale dans les trois maladies. Une comparaison avec les données de primates non humains traités par antipsychotiques suggère que ces médicaments sont peu enclins à booster l’expression génétique mais plutôt à la normaliser partiellement, expliquent les chercheurs.

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