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

Abstract

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.

Altered intrinsic brain activity in patients with hepatic encephalopathy

“…This checklist was developed based on quality assessment tools for observational studies and was applied in previous meta-analyses focusing on MRI variables (Ma et al, 2019;Wang et al, 2016).…”

Emotion processing and regulation in major depressive disorder: A 7T resting-state fMRI study

“…Previous MDD meta-analyses pointed to higher activation of amygdala during exposure to negative stimuli (Hamilton et al, 2012;Palmer et al, 2015). The elevated ALFF of amygdala also observed in a resting-state meta-analysis (Ma et al, 2019) which probably provide the susceptibility for prolonged/excessive processing of negative information. Of note, there is evidence that amygdala activity is affected by clinical confounders, that is, symptom severity, state/trait anxiety and medication level (Brakowski et al, 2017;Li et al, 2018) which render inconsistent findings across resting-state studies (Gray et al, 2020;Li et al, 2017;Zhou et al, 2017).…”

“…Affective dysfunctions in MDD can be also observed in localizable and whole-brain resting-state fMRI metrics e.g., amplitude of low frequency fluctuations (ALFF) (Cheng et al, 2019;Song, Shen, Mu, Mao, & Wang, 2020) and functional connectivity (FC) (He et al, 2019;Song, Zhang, & Huang, 2016). Neuroimaging meta-analyses on ALFF studies pointed to accentuated processing of salient information in the insula/ACC (Li et al, 2017;Wang et al, 2017;Zhou et al, 2017), augmented emotional reactivity in the amygdala (Ma et al, 2019) and diminished cognitive control in the prefrontal cortex (Wang et al, 2017;Zhong, Pu, & Yao, 2016) (Also see (Gray, Müller, Eickhoff, & Fox, 2020) which did not replicate previous ALFF findings in MDD). In addition, a previous review (Mulders, van Eijndhoven, Schene, Beckmann, & Tendolkar, 2015) and a meta-analysis (Kaiser, Andrews-Hanna, Wager, & Pizzagalli, 2015) showed altered FC in the neural networks underlying the processing and cognitive control of emotions.…”

Emotion processing and regulation in major depressive disorder: A 7T resting‐state fMRI study

“…Previous MDD meta‐analyses pointed to higher activation of amygdala during exposure to negative stimuli (Hamilton et al, 2012; Palmer et al, 2015). The elevated ALFF of amygdala also observed in a resting‐state meta‐analysis (Ma et al, 2019) which probably provide the susceptibility for prolonged/excessive processing of negative information. Of note, there is evidence that amygdala activity is affected by clinical confounders, that is, symptom severity, state/trait anxiety and medication level (Brakowski et al, 2017; Li et al, 2018) which render inconsistent findings across resting‐state studies (Gray et al, 2020; Li et al, 2017; Zhou et al, 2017).…”

“…Affective dysfunctions in MDD can be also observed in localizable and whole‐brain resting‐state fMRI metrics e.g., amplitude of low frequency fluctuations (ALFF) (Cheng et al, 2019; Song, Shen, Mu, Mao, & Wang, 2020) and functional connectivity (FC) (He et al, 2019; Song, Zhang, & Huang, 2016). Neuroimaging meta‐analyses on ALFF studies pointed to accentuated processing of salient information in the insula/ACC (Li et al, 2017; Wang et al, 2017; Zhou et al, 2017), augmented emotional reactivity in the amygdala (Ma et al, 2019) and diminished cognitive control in the prefrontal cortex (Wang et al, 2017; Zhong, Pu, & Yao, 2016) (Also see (Gray, Müller, Eickhoff, & Fox, 2020) which did not replicate previous ALFF findings in MDD). In addition, a previous review (Mulders, van Eijndhoven, Schene, Beckmann, & Tendolkar, 2015) and a meta‐analysis (Kaiser, Andrews‐Hanna, Wager, & Pizzagalli, 2015) showed altered FC in the neural networks underlying the processing and cognitive control of emotions.…”