Altered functional connectivity networks of hippocampal subregions in remitted late-onset depression: a longitudinal resting-state study

The regional specificity of hippocampal abnormalities in late-life depression (LLD) has been demonstrated in previous studies. In this study, we sought to examine the functional connectivity (FC) patterns of hippocampal subregions in remitted late-onset depression (rLOD), a special subtype of LLD. Fourteen rLOD patients and 18 healthy controls underwent clinical and cognitive evaluations as well as resting-state functional magnetic resonance imaging scans at baseline and at similar to 21 months of follow-up. Each hippocampus was divided into three parts, the cornu ammonis (CA), the dentate gyrus, and the subicular complex, and then six seed-based hippocampal subregional networks were established. Longitudinal changes of the six networks over time were directly compared between the rLOD and control groups. From baseline to follow-up, the rLOD group showed a greater decline in connectivity of the left CA to the bilateral posterior cingulate cortex/precuneus (PCC/PCUN), but showed increased connectivity of the right hippocampal subregional networks with the frontal cortex (bilateral medial prefrontal cortex/anterior cingulate cortex and supplementary motor area). Further correlative analyses revealed that the longitudinal changes in FC between the left CA and PCC/PCUN were positively correlated with longitudinal changes in the Symbol Digit Modalities Test (r = 0.624, P = 0.017) and the Digit Span Test (r = 0.545, P = 0.044) scores in the rLOD group. These results may provide insights into the neurobiological mechanism underlying the cognitive dysfunction in rLOD patients.