The BDNF Val66Met polymorphism, resting-state hippocampal functional connectivity and cognitive deficits in acute late-onset depression

Objective: To investigate the relationship between hippocampal functional connectivity (HFC), cognitive deficits, and the influence of BDNF Val66Met polymorphism on the HFC in acute late-onset depression (LOD).

Methods: 26 LOD patients and 33 and normal controls (NCs) completed clinical assessments, neuropsychological testing, blood samples collecting for genotyping, and resting-state functional MRI (R-fMRI) scans. The LOD and NCs groups were further divided into four groups according to BDNF Met allele carrier or not (LOD Met-(n=8); LOD Met+(n=18); NCs Met-(n=9); NCs Met+(n=24)). Then, seed-based correlation analyses and two-way analysis of covariance (ANCOVA) were performed to explore the main effects and interactive effects of LOD and BDNF Val66Met polymorphism on the HFC. Spearman correlation was applied to examine the cognitive and emotional significance of these altered HFC networks.

Results: Compared with NCs, bilateral positive HFC with the right insula, left positive HFC with bilateral orbit-frontal cortex (OFC) and left precuneus, right positive HFC with right dorsolateral prefrontal cortex (dlPFC) were decreased, and bilateral negative HFC with right postcentral gyrus were reversed in LOD patients. BDNF Met allele mainly decreased bilateral positive HFC with the cerebellum. The interaction of LOD and BDNF Met allele primarily influenced the bilateral HFC with the temporal cortex and dorsal nexus. The changed HFC with the OFC, postcentral gyrus, cerebellum and temporal cortex significantly correlated to the cognitive deterioration. There was no significant association between the depressive severity and any altered HFC networks.

Conclusion: The cognitive deterioration in LOD patients, BDNF Met allele carriers, and LOD patients carring Met allele were associated with the changed HFC networks in the OFC/postcentral gyrus, cerebellum and temporal cortex respectively.