The association between gray matter volume in the hippocampal subfield and antidepressant efficacy mediated by abnormal dynamic functional connectivity

Abstract

An abnormality of structures and functions in the hippocampus may have a key role in the pathophysiology of major depressive disorder (MDD). However, it is unclear whether structure factors of the hippocampus effectively impact antidepressant responses by hippocampal functional activity in MDD patients. We collected longitudinal data from 36 MDD patients before and after a 3-month course of antidepressant pharmacotherapy. Additionally, we obtained baseline data from 43 healthy controls matched for sex and age. Using resting-state functional magnetic resonance imaging (rs-fMRI), we estimated the dynamic functional connectivity (dFC) of the hippocampal subregions using a sliding-window method. The gray matter volume was calculated using voxel-based morphometry (VBM). The results indicated that patients with MDD exhibited significantly lower dFC of the left rostral hippocampus (rHipp.L) with the right precentral gyrus, left superior temporal gyrus and left postcentral gyrus compared to healthy controls at baseline. In MDD patients, the dFC of the rHipp.L with right precentral gyrus at baseline was correlated with both the rHipp.L volume and HAMD remission rate, and also mediated the effects of the rHipp.L volume on antidepressant performance. Our findings suggested that the interaction between hippocampal structure and functional activity might affect antidepressant performance, which provided a novel insight into the hippocampus-related neurobiological mechanism of MDD.

Figure 1

Four hippocampal subregions. The red cluster marked is our region of interest. Abbreviations: rHipp.L, the left rostral hippocampus.

Figure 2

(a) Between-group differences of the relative volume of rHiopp.L; (b) Between-group differences mean dFC of rHipp.L with PreCG.R. Abbreviations: MDD, major depressive disorder; rHipp.L, the left rostral hippocampus; dFC, dynamic functional connectivity; PreCG.R, the right precentral gyrus.

Figure 3

Correlation and mediation analysis. (a) The mean dFC of the rHipp.L with PreCG.R at baseline was correlated with the relative volume of rHiopp.L; (b) The mean dFC of the rHipp.L with PreCG.R at baseline was correlated with HAMD remission rate; (c) The mean dFC at baseline between the rHipp.L and PreCG.R significantly mediates the relationship between the relative rHipp.L volume at baseline and HAMD RR [Indirect effect c’ = − 0.118 95% CI [− 0.387, − 0.003], Direct effect c’ = 0.007, Total effect c = − 0.111]. Abbreviations: dFC, dynamic functional connectivity; rHipp.L, the left rostral hippocampus; PreCG.R, the right precentral gyrus; HAMD, Hamilton Depression Rating Scale; RR, remission rate; CI, confidence interval.