Sad Mood in Late-Life Depression Correlates With Reduced Thickness in Orbitofrontal Cortex

Late-life depression (LLD) is a heterogeneous psychiatric condition characterized by a wide range of psychopathological symptoms and associated with functional and structural abnormalities in brain networks implicated in mood and cognitive regulation. This cross-sectional study investigated the relationship between specific depressive symptom dimensions and cortical brain measures, as assessed by magnetic resonance imaging, in a sample of 87 community-dwelling older adults with depression.

Significant associations were identified between the severity of sad mood and reduced cortical volume in the right medial orbitofrontal cortex (OFC) (p [FDR] = 0.047), as well as reduced cortical thickness in the left OFC (p [FDR] = 0.008), left ventrolateral prefrontal cortex (VLPFC) (p [FDR] = 0.02), and right dorsolateral prefrontal cortex (DLPFC) (p [FDR] = 0.054). Apathy/lassitude was also significantly associated with reduced thickness in the left OFC (p [FDR] = 0.016) and left VLPFC (p [FDR] = 0.046). Moreover, overall depression severity correlated with reduced thickness in the right middle temporal cortex (MTC) (p [FDR] = 0.035).

Our results suggest that feelings of low mood and lassitude in LLD are linked to structural changes in brain regions involved in emotion regulation, motivational drive, self-referential thinking, executive control, and decision-making. The findings contribute to the understanding of the neurobiological underpinnings of LLD and support the hypothesis that symptom-specific disruptions within mood and cognitive processing circuits are integral to its pathophysiology.