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Background:  There is an urgent need for a meta-analysis that characterizes the brain states of major depression disorder (MDD) patients and potentially provides reliable biomarkers, because heterogeneity in the results of resting-state functional neuroimaging has been observed between studies, with some patients not showing the consistent changes, or even opposite patterns. Thus, we evaluated consistent regional brain activity alterations in medication-naive patients with first-episode unipolar MDD and compared the results with those in healthy controls (HCs).   Methods:  A systematic database search was conducted (in PubMed, Ovid, and Web of Knowledge) between January 1984 and July 2016 to select resting-state functional activity studies with a voxel-wise analysis in MDD. We used anisotropic effect size-signed differential mapping to perform a whole-brain meta-analysis, comparing functional alterations between first-episode medication-naive unipolar MDD patients and HCs by integrating the studies. In addition, subgroup meta-analysis was conducted to control for the MRI analysis method. Moreover, the meta-regression analyses were performed to examine the potential effects of mean age, education duration, illness duration, and severity of depressive symptoms.   Results:  A total of 12 studies were included, comparing 313 MDD patients with 283 HCs. The pooled and subgroup meta-analysis found that the MDD patients showed hyperactivity in the left parahippocampal gyrus, left supplementary motor area, left amygdala, left hippocampus, and left middle frontal gyrus (MFG; orbital part), and hypoactivity in the left lingual gyrus, left middle occipital gyrus, right cuneus cortex, right MFG (orbital part), and left cerebellum. In the meta-regression analyses, the mean illness duration was positively associated with hyper-activation in the left parahippocampal gyrus and hypoactivation in the hemispheric lobule IV/V of the left cerebellum.   Conclusions:  This meta-analysis indicated that MDD patients had significant and robust resting-state brain activity alteration in amygdala, left hippocampus and other regions, which implicated this finding in the pathophysiology of cognitive and emotional impairment in MDD patients.

frontiers in behavioral neuroscience

Altered Resting-State Functional Activity in Medication-Naive Patients With First-Episode Major Depression Disorder vs. Healthy Control: A Quantitative Meta-Analysis