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

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.

Linking inter-subject variability of cerebellar functional connectome to clinical symptoms in major depressive disorder.

Major depressive disorder (MDD) is a highly prevalent psychiatric disorder with remarkable inter-subject variability in clinical manifestations. Neuroimaging changes of the cerebellum have been recently proposed as a way to characterize MDD-related brain disruptions and might further explain various clinical symptoms. However, the cerebellar contributions to MDD clinical heterogeneity remain largely unknown. The analyzed data consisted of 251 MDD patients and 235 matching healthy controls (HC). The inter-subject variability of functional connectomes (IVFC) was estimated via Pearson's correlation analysis between each pair of the cerebellar and cerebral regions based on resting-state functional magnetic resonance imaging (rs-fMRI). A partial least squares (PLS) regression analysis was performed to determine the potential dimension linking the IVFC to clinical symptom measures. The results indicated that similar spatial distribution patterns of the cerebellar IVFC were observed between MDD and HC, but the MDD group exhibited abnormal IVFC alterations in the bilateral Cerebelum_4_5, bilateral Cerebelum_6, Vermis_1_2 and Vermis_8. The PLS model revealed that the IVFC pattern in the left Cerebelum_6 was significantly associated with three HAMD-17 items including the work and activities, psychomotor retardation, and depressed mood. These findings provided new evidence for the cerebellar changes in MDD. Specifically, we found that the altered inter-subject variability measurements correlated with clinical manifestations of this illness. Elucidating this variability could prove helpful for the evaluation of MDD heterogeneity as well as for understanding its pathophysiological mechanism.