Neuroticism mediates the link of resting-state brain activity and connectivity to subthreshold depression in older...

The neurobiology of subthreshold depression, a prevalent and debilitating condition among older women, remains poorly understood. Neuroticism is a known depression risk factor, yet its role in linking brain function to depressive symptoms in this population is understudied. This study investigated neurofunctional alterations in older women with subthreshold depression and tested whether neuroticism statistically explains the link between neural alterations and depressive symptoms.

50 older women with subthreshold depression and 52 healthy older women controls underwent resting-state fMRI. Amplitude of low-frequency fluctuations (ALFF) and seed-based resting-state functional connectivity (RSFC) were analyzed. Depressive symptoms were assessed using the Geriatric Depression Scale and Center for Epidemiologic Studies Depression Scale, and personality traits with the Big Five Inventory-2. Mediation analyses examined the indirect effects of neuroticism.

Compared to controls, older women with subthreshold depression showed higher depression and neuroticism scores and lower scores on other personality traits. Neuroimaging revealed greater ALFF in the left lateral orbitofrontal cortex (LOFC) and increased RSFC between the LOFC and medial OFC (MOFC) in the subthreshold depression group. These neural alterations positively correlated with depressive symptoms across all participants. Notably, only neuroticism correlated with both LOFC ALFF and LOFC-MOFC RSFC, and positively mediated the link between these neural markers and depressive symptoms.

Older women with subthreshold depression exhibit OFC dysfunction, with neuroticism mediating the link to depressive symptoms. These findings elucidate a neuropsychological pathway linking intrinsic brain function to depressive symptomatology via personality vulnerability, offering potential targets for early identification and intervention in this at-risk population.