Background
The increasingly compelling data supporting the involvement of immunobiological mechanisms in Major Depressive Disorder (MDD) might provide some explanation of the variance in this heterogeneous condition. Peripheral blood measures of cytokines and chemokines constitute the bulk of evidence with consistent meta-analytic data implicating raised proinflammatory cytokines such as IL6, IL1β and TNF. Among the potential mechanisms linking immunobiological changes to affective neurobiology is the accelerated biological ageing seen in MDD, particularly via the senescence associated secretory phenotype (SASP). However, the cellular source of immunobiological markers remains unclear.
Aims
Pre-clinical evidence suggests a role for peripheral blood mononuclear cells (PBMC), thus here we aimed to explore the transcriptomic profile using RNA sequencing in PBMCs in a clinical sample of people with various levels of depression and treatment response comparing it with that in healthy controls (HCs).
Method
Transcriptomic analysis of peripheral blood mononuclear cells.
Results
The data showed no robust signal differentiating MDD and HCs. There was, however, significant evidence of elevated biological ageing in MDD vs HC.
Conclusions
Future work should endeavour to expand clinical sample sizes and reduce clinical heterogeneity. The exploration of RNA-seq signatures in other leukocyte populations and advances in RNA sequencing at the level of the single cell may help uncover more subtle differences. However, currently the subtlety of any PBMC signature mitigates against its convincing use as a diagnostic or predictive biomarker.
No evidence for differential gene expression in major depressive disorder PBMCs, but robust evidence of elevated biological ageing.