Peripheral blood transcriptomic differences predict depression status in individuals undergoing bariatric surgery

More than one third of candidates for bariatric surgery suffer with clinical depression. Significant reduction in depression following bariatric surgery has been shown, but this is not consistent for all patients. The biological mechanisms behind the association between obesity and depression and behind persistent/remitted depression post-surgery remain unclear. This study aimed to identify potential biological mechanisms involved in this association. As part of the longitudinal observational bariatric surgery and depression (BARIDEP) study, blood samples were collected from individuals prior to bariatric surgery. For this study we selected n = 29 subjects (from the original sample of n = 85 participants) based on their Hamilton Depression (HAM-D) scale scores at baseline and at 6 months post-surgery and grouped them as controls (n = 10), persistent depression (n = 7) or remission (n = 12). Participants were selected to be matched for age, sex and BMI. RNA was extracted and bulk RNAseq was performed. Data were analysed for differential expression and gene set enrichment across the 3 groups of interest. Analysis of the differential gene expression showed seven genes differentially expressed across the three groups, with genes mainly involved in immune activation or synaptic function. The greatest differences were found between the persistent and remitting depression groups, despite both experiencing clinical depression at the time of sample collection. Our data show distinct baseline gene expression and gene enrichment suggesting different immune and metabolic mechanisms possibly involved in persistent vs remitting depression post-bariatric surgery.