Regional cerebral metabolism alterations affect resting-state functional connectivity in major depressive disorder.

Background: F-FDG positron emission tomography (PET) is a reliable technique to quantify regional neural glucose metabolism even with major depressive disorder (MDD) heterogeneous features. Previous study proposed that in the resting-state (RS), pairs of brain regions whose regional glucose metabolic rates were significantly correlated were functionally associated. This synchronicity indicates a neuronal metabolic and functional interaction in high energy efficient brain regions. In this study, a multimode method was used to identify the RS-FC patterns based on regional metabolism changes, and to observe its relationship with the severity of depressive symptoms in MDD patients.

Methods: The study enrolled 11 medication-naive MDD patients and 14 healthy subjects. All participants received a static F-FDG PET brain scan and a resting-state functional magnetic resonance imaging (RS-fMRI) scan. SPM5 software was used to compare brain metabolism in MDD patients with that in healthy controls, and designated regions with a change in metabolism as regions of interest (ROIs). The glucose metabolism-based regional RS-FC Z values were compared between groups. Then group independent component analysis (ICA) was used to identify the abnormal connectivity nodes in the intrinsic function networks. Finally, the correlation between abnormal RS-FC Z values and the severity of depressive symptoms was evaluated.

Results: Patients with MDD had reduced glucose metabolism in the putamen, claustrum, insular, inferior frontal gyrus, and supramarginal gyrus. The metabolic reduction regions impaired functional connectivity (FC) to key hubs, such as the Inferior frontal gyrus (pars triangular), angular gyrus, calcarine sulcus, middle frontal gyrus (MFG), located in dorsolateral prefrontal cortex (DLPFC)/parietal lobe, salience network (SN), primary visual cortex (V1), and language network respectively. There was no correlation between aberrant connectivity and the severity of clinical symptoms.

Conclusions: This research puts forward a possibility that focal neural activity alteration may share RS-FC dysfunction and be susceptible to hubs in the functional network in MDD. In particular, the metabolism and function profiles of the Inferior frontal gyrus (pars triangularis) should be emphasized in future MDD studies.