Abstract summary 

22q11.2 deletion is the most prominent risk factor for schizophrenia (SZ). The aim of the present study was to identify unique transcriptome profile for 22q11.2 deletion syndrome (DS)-related SZ spectrum disorder (SZ-SD). We performed RNA-Seq screening in lymphoblasts collected from 20 individuals with 22q11.2DS (10 men and 10 women, 4 of each sex with SZ-SD and 6 with no psychotic disorders (Np)). Sex effect in RNA-Seq descriptive analysis led to separating the analyses between men and women. In women, only one differentially expressed gene (DEG), was associated with SZ-SD. In men, 48 DEGs (adjp < 0.05) were found to be associated with SZ-SD. Ingenuity pathway analysis of top 85 DEGs (p < 4.66E-04) indicated significant enrichment for immune-inflammatory response (IIR) and neuro-inflammatory signaling pathways. Additionally, NFATC2, IFNG, IFN-alpha, STAT1 and IL-4 were identified as upstream regulators. Co-expression network analysis revealed the contribution of endoplasmic reticulum protein processing and N-Glycan biosynthesis. These findings indicate dysregulation of IIR and post-translational protein modification processes in individuals with 22q11.2DS-related SZ-SD. Candidate pathways and upstream regulators may serve as novel biomarkers and treatment targets for SZ. Future transcriptome studies, including larger samples and proteomic analysis, are needed to substantiate our findings.

Authors & Co-authors:  Michaelovsky Carmel Gothelf Weizman

Study Outcome 

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