Characterization of brain blood flow and the amplitude of low-frequency fluctuations in major depressive disorder: A multimodal meta-analysis

Abstract

Background: In healthy subjects, there is an association between amplitude of low-frequency fluctuations (ALFF) and regional cerebral blood flow (rCBF). To date, no published meta-analysis has investigated changes in the regional ALFF in medication-free depressed patients.

Methods: In this study, we aimed to explore whether resting-state rCBF and ALFF changes co-occur in the depressed brain without the potential confound of medication. Using signed differential mapping (SDM), we conducted two meta-analyses, one of rCBF studies and one of ALFF studies, involving medication-free patients with major depressive disorder (MDD). In addition, we conducted a multimodal meta-analysis to identify brain regions that showed abnormalities in both rCBF and ALFF.

Results: A total of 16 studies were included in this series. We identified abnormalities in resting-state rCBF and ALFF in the left insula in medication-free MDD patients compared with healthy controls (HC). In addition, we observed altered resting-state rCBF in the limbic-subcortical-cortical circuit and altered ALFF in the default mode network (DMN) and some motor-related brain regions.

Limitations: The analysis techniques, patient characteristics and clinical variables of the included studies were heterogeneous.

Conclusions: The conjoint alterations in ALFF and rCBF in the left insula may represent core neuropathological changes in medication-free patients with MDD and merit further studying.

Keywords: Amplitude of low-frequency fluctuations; Insula; Major depressive disorder; Multimodal analysis; Regional cerebral blood flow; fMRI.