Left Cerebellar‐Right Frontal Uncoupling in Female First‐Episode Major Depressive Disorder: Synaptic Evidence From [ 18F]UCB‐H PET

Abstract

ABSTRACT Background Synaptic loss is a neuropathological feature of depression. Objective Cerebello‐cerebral synaptic function was evaluated in female first‐episode major depressive disorder (MDD) patients using [18F]UCB‐H positron emission tomography (PET). Materials and Methods PET was performed on female first‐episode MDD patients (FMD group, n = 7), healthy controls (HC group, n = 9), and chronic restraint stress (CRS) mice (n = 9). Standardized uptake value ratios (SUVR), voxel‐wise tracer uptake analysis, functional connectivity (FC), and network analysis were performed at the cerebello‐cerebral level. Associations with Hamilton depression scale (HAMD) and Hamilton anxiety scale (HAMA) scores were assessed by Pearson correlation and logistic regression analysis. Results In the FMD group, SUVR in the left cerebellum 7b was significantly reduced and negatively correlated with HAMD (r = −0.57) and HAMA (r = −0.55) scores. The cluster centered on the left cerebellar lobule VIII showed reduced tracer uptake and was negatively correlated with HAMD scores. FC was significantly reduced in the right frontal lobe but enhanced in the midbrain and occipital regions. The network was characterized by bilateral frontal lobe concentration in the FMD group, while the cerebellar network was more uniform. Cerebello‐cerebral uncoupling between the left cerebellum and the right frontal lobe was observed, manifested as reduced SUVR correlation and weakened FC. CRS mice also showed reduced brain [18F]UCB‐H uptake. Conclusions Left cerebellar‐right frontal uncoupling may serve as a potential neural correlate of first‐episode MDD in females.