Are resting-state network alterations in late-life depression related to synaptic density? Findings of a combined 11C-UCB-J PET and fMRI study

This study investigates the relationship between resting-state functional magnetic resonance imaging (rs-fMRI) topological properties and synaptic vesicle glycoprotein 2A (SV2A) positron emission tomography (PET) synaptic density (SD) in late-life depression (LLD). 18 LLD patients and 33 healthy controls underwent rs-fMRI, 3D T1-weighted MRI, and 11C-UCB-J PET scans to assess SD. The rs-fMRI data were utilized to construct weighted networks for calculating four global topological metrics, including clustering coefficient, characteristic path length, global efficiency, and small-worldness, and six nodal metrics, including nodal clustering coefficient, nodal characteristic path length, nodal degree, nodal strength, local efficiency, and betweenness centrality. The 11C-UCB-J PET provided standardized uptake value ratios as SD measures. LLD patients exhibited preserved global topological organization, with reduced nodal properties in regions associated with LLD, such as the medial prefrontal cortex (mPFC), and increased nodal properties in the basal ganglia and cerebellar regions. Notably, a negative correlation was observed between betweenness centrality in the mPFC and depressive symptom severity. No significant alterations in SD or associations between rs-fMRI topological properties and SD were found, challenging the hypothesis that SD alterations are the molecular basis for rs-fMRI topological changes in LLD. Our findings suggest other molecular mechanisms may underlie the observed functional connectivity alterations in these patients.