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

- First meta-analysis of CBF and ALFF studies in medication-free MDD patients.
- The dysfunction of insula represent core neuropathological changes in MDD.
- The limbic-subcortical-cortical circuit and default mode network are affected in MDD.

BackgroundIn 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.MethodsIn 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.ResultsA 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.LimitationsThe analysis techniques, patient characteristics and clinical variables of the included studies were heterogeneous.ConclusionsThe 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.