Replicable and robust cellular and biochemical blood marker signatures of depression and depressive symptoms

Identification of replicable and robust peripheral blood-based markers associated with depression remains elusive, given that studies frequently identify potential biomarkers that ultimately fail to replicate in other studies, impeding progress in psychiatric research. Peripheral biochemical and cellular markers (PBCs; e.g., albumin) may play an important role in depression.

Using a test-replication design including participants from the NHANES community cohort (n_test=17,450, n_replication=17,449), we examined 42 PBCs to identify PBCs that were both replicably and robustly associated with either overall depression severity or individual symptoms of depression across both cohorts across a wide range of possible combinations of analytic decisions (n's = 17,000+).

We found that a small set of PBCs (e.g., bilirubin) were robustly and replicably associated with overall depression severity, with unique signatures of PBCs linked with individual symptoms of depression when stratified by gender. A varying degree of correlation was found between measures of replicability.

We identified replicable and robust cellular biochemical blood marker signatures associated with both overall depression severity and individual symptoms of depression. Our findings can be used to enhance other researchers' abilities to better understand factors associated with depression and potentially drive the development of effective treatments for depression.