Differences in olfactory functional connectivity in early-onset depression and late-onset depression

Late-onset depression (LOD) and early-onset depression (EOD) exhibit different pathological mechanisms and clinical phenotypes, including different extents of olfactory dysfunction. However, the brain abnormalities underlying the differences in olfactory dysfunction between EOD and LOD remain unclear. The aim of this study was to compare the functional connectivity (FC) patterns of olfactory regions between EOD patients and LOD patients and examine their relationship with cognitive function. One hundred five patients with EOD, 101 patients with LOD and 160 normal controls (NCs) were recruited for the present study. Subjects underwent clinical assessment, olfactory testing, cognitive assessments and magnetic resonance imaging. Eight regions of the primary and secondary olfactory regions were selected to investigate olfactory FC. Patients with LOD exhibited decreased odor identification (OI) compared with patients with EOD and NCs. The LOD group exhibited decreased FC compared with the EOD and NC groups when primary and secondary olfactory regions were selected as the regions of interest (the piriform cortex, lateral entorhinal cortex and orbital-frontal cortex). Additionally, these abnormal olfactory FCs were associated with decreased cognitive function scores and OI, and the FC between the left orbital-frontal cortex and left amygdala was a partial mediator of the relationship between global cognitive scores and OI. Overall, patients with LOD exhibited decreased FC in both the primary and secondary olfactory cortices compared with patients with EOD, and abnormal olfactory FC was associated with OI dysfunction and cognitive impairment. The FC between the orbital-frontal cortex and amygdala mediated the relationship between global cognitive function and OI.