0 avis
Immune-Related Genetic Overlap Between Regional Gray Matter Reductions and Psychiatric Symptoms in Adolescents, and Gene-Set Validation in a Translational Model
Archive ouverte
International audience. Adolescence is a period of vulnerability for the maturation of gray matter (GM) and alsofor the onset of psychiatric disorders such as major depressive disorder (MDD), bipolardisorder and schizophrenia. Chronic neuroinflammation is considered to play a role inthe etiology of these illnesses. However, the involvement of neuroinflammation in theobserved link between regional GM volume reductions and psychiatric symptoms is notestablished yet. Here, we investigated a possible common immune-related genetic linkbetween these two phenomena in european adolescents recruited from the community.Hippocampal and medial prefrontal cortex (mPFC) were defined a priori as regionsof interest (ROIs). Their GM volumes were extracted in 1,563 14-year-olds from theIMAGEN database. We found a set of 26 SNPs that correlated with the hippocampalvolumes and 29 with the mPFC volumes at age 14. We formed two ROI-RelatedImmune-gene scores (RRI) with the inflammation SNPs that correlated to hippocampalGM volume and to mPFC GM volume. The predictive ability of both RRIs with regards tothe presence of psychiatric symptoms at age 18 was investigated by correlating the RRIswith psychometric questionnaires obtained at age 18. The RRIs (but not control scoresconstructed with random SNPs) correlated with the presence of depressive symptoms,positive psychotic symptoms, and externalizing symptoms in later adolescence. Inaddition, the effect of childhood maltreatment, one of the major environmental riskfactors for depression and other mental disorders, interacted with the RRI effect. Wenext sought to validate this finding by investigating our set of inflammatory genes ina translational animal model of early life adversity. Mice were subjected to a protocolof maternal separation at an early post-natal age. We evaluated depressive behaviorsin separated and non-separated mice at adolescence and their correlations with theconcomitant expression of our genes in whole blood samples. We show that in mice,early life adversity affected the expression of our set of genes in peripheral blood, andthat levels of expression correlated with symptoms of negative affect in adolescence.Overall, our translational findings in adolescent mice and humans provide a novelvalidated gene-set of immune-related genes for further research in the early stages ofmood disorders.
Consulter en ligne
Suggestions
Du même auteur
