Proteomic Features and Association Analysis of Late-Onset Depression Based on Behavioral Factorial Analysis and Proteomics.

Late-onset depression (LOD) is a common subtype of depression in the elderly, characterized by high disability and recurrence rates, along with poorly understood biological correlates, posing a serious threat to the health of the aging population; moreover, the molecular correlates and diagnostic targets for LOD remain largely unknown. Aging and stress are recognized as two core risk factors for LOD; however, whether they interact and how such interaction is associated with the depressive phenotype remain unclear, so we established a rat model of LOD to analyze the interactive effects of aging and stress on depressive-like behaviors, and combined this with cerebrospinal fluid proteomics to explore potential protein correlates and provide experimental evidence for identifying candidate therapeutic targets. In terms of results, aging and stress exhibited a synergistic association with depressive-like behaviors in LOD rats, and enrichment was observed in extracellular matrix and sphingolipid metabolic pathways; furthermore, several proteins─including ceramide, MMP2, TIMP2, SPARC, FBN1, and collagen─were identified as candidate correlates worthy of further investigation. In conclusion, stress and aging exert interactive effects on behavioral phenotypes in LOD rats, with associated alterations in extracellular matrix and sphingolipid pathways, and key molecules including Cer, MMP2, Timp2, and Sparc warrant further investigation.