Sex and the interaction with the proteomic signature of depression

Differences in the prevalence and burden of depression among women have been extensively documented, proving stable across culture, age, and time. Towards characterizing sexual dimorphism in the proteomics of depression, this investigation evaluated the serum levels of over 7,500 analytes on the SomaLogic SomaScan proteomic assay in 75 moderately to severely depressed patients enriched for endogenomorphic symptoms and 78 healthy controls. Combining differential expression and pathway enrichment analyses, the distribution of sex-dependent protein expression in depressed males and females was compared, and significantly sex-dependent proteins are explored. Differential protein expression results are used to inform the development of classifiers distinguishing between depressed patients and healthy controls.
An equal number of differentially expressed proteins were found between males and females, with males displaying more proteins with increased expression in cases versus controls and the opposite observed among females. The immune system was the only overrepresented pathway among the proteins with significant sex-dependent expression in depression. Individual examination of immune-identified proteins highlighted multiple proteins not previously associated with depression. Together, these proteins exhibited bidirectional support for alterations of immune and inflammatory protein expression between males and females. Results from classifier development showed that leveraging differentially expressed proteins resulted in improved classifier performance.
These findings have implications for research on therapeutic targets in depression and classifier development. Future investigations should elaborate on these findings through studies with larger sample sizes of phenotypically diverse cohorts.