Objectives To investigate immune dysregulation in major depressive disorder (MDD) and schizophrenia (SZ) at single-cell resolution and to determine associations between immune-related transcriptional signatures and clinical symptoms of depression. Design Cross-sectional case–control study integrating cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) of peripheral blood mononuclear cells (PBMCs). Setting Single-centre study conducted at a tertiary psychiatric care in Germany. Participants Patients with MDD (n=22), patients with SZ (n=10) and healthy controls (n=26). Interventions None. Main outcome measures Single-cell transcriptomic and epitope profiles of PBMCs, differential gene expression, cell composition changes, pathway enrichment and correlations between gene expression and Beck Depression Inventory-II (BDI-II) symptom scores. Results CITE-seq analysis yielded 633 284 high-quality single-cell profiles. Disease-specific transcriptomic signatures were identified for both MDD and SZ, alongside shared profiles between the disorders. Patients with MDD showed elevated monocyte numbers and enrichment of interferon (IFN) signalling pathways. Similar IFN-related alterations were observed in monocytes from patients with SZ, suggesting shared immune mechanisms. In MDD, transcriptional alterations across peripheral immune cell types correlate strongly with depressive symptoms, including sadness and pessimism. Reactome pathway analysis identified nuclear factor kappa-light-chain-enhancer of activated B cell-associated pathways among genes positively associated with disease symptoms and traits. CITE-Seq of PBMCs. Conclusions Peripheral immune alterations in psychiatric disorders are reflected by distinct and shared single-cell transcriptional signatures. The identified associations between immune-related pathways and depressive symptom profiles may support patient stratification and facilitate the development of more targeted therapeutic approaches for psychiatric disorders.
Meier et al. (Wed,) studied this question.