Age-Related Decrease in Default-Mode Network Functional Connectivity Is Accelerated in Patients With Major Depressive Disorder.

Shixiong Tang,Xudong Chen,Yicheng Long,Hengyi Cao,Guowei Wu,Jie Yang,Dayi Liu,Wenjian Tan,Zhening Liu,Zhipeng Wu

doi:10.3389/fnagi.2021.809853

Abstract

Major depressive disorder (MDD) is a common psychiatric disorder which is associated with an accelerated biological aging. However, little is known whether such process would be reflected by a more rapid aging of the brain function. In this study, we tested the hypothesis that MDD would be characterized by accelerated aging of the brain’s default-mode network (DMN) functions. Resting-state functional magnetic resonance imaging data of 971 MDD patients and 902 healthy controls (HCs) was analyzed, which was drawn from a publicly accessible, multicenter dataset in China. Strength of functional connectivity (FC) and temporal variability of dynamic functional connectivity (dFC) within the DMN were calculated. Age-related effects on FC/dFC were estimated by linear regression models with age, diagnosis, and diagnosis-by-age interaction as variables of interest, controlling for sex, education, site, and head motion effects. The regression models revealed (1) a significant main effect of age in the predictions of both FC strength and dFC variability; and (2) a significant main effect of diagnosis and a significant diagnosis-by-age interaction in the prediction of FC strength, which was driven by stronger negative correlation between age and FC strength in MDD patients. Our results suggest that (1) both healthy participants and MDD patients experience decrease in DMN FC strength and increase in DMN dFC variability along age; and (2) age-related decrease in DMN FC strength may occur at a faster rate in MDD patients than in HCs. However, further longitudinal studies are still needed to understand the causation between MDD and accelerated aging of brain.

Highlights

Major depressive disorder (MDD), one of the most common serious psychiatric disorders worldwide, is associated with increased risks of many biological and physiological pathologies such as dementia/cognitive decline (Byers and Yaffe, 2011; Holmquist et al, 2020), cardiovascular disease (Gan et al, 2014), and osteoporosis (Cizza et al, 2009) which occur in the process of normal aging
The linear regression model revealed a significant main effect of age (β = −0.182, t = −6.115, p < 0.001) in the prediction of default-mode network (DMN) functional connectivity (FC) strength, suggesting that both MDD patients and healthy controls (HCs) experienced a similar reduction in DMN FC with age
The first main finding revealed by regression model in the present study is a significant main effect of age in the prediction of both FC strength and dynamic functional connectivity (dFC) variability within the DMN

Summary

Introduction

Major depressive disorder (MDD), one of the most common serious psychiatric disorders worldwide, is associated with increased risks of many biological and physiological pathologies such as dementia/cognitive decline (Byers and Yaffe, 2011; Holmquist et al, 2020), cardiovascular disease (Gan et al, 2014), and osteoporosis (Cizza et al, 2009) which occur in the process of normal aging. In previous fMRI studies, the most prominent and frequently reported findings in MDD are altered resting-state functional connectivity (FC) patterns within the default-mode network (DMN) areas (Mulders et al, 2015; Zhang K. et al, 2016; Zanatta et al, 2019; Shi et al, 2021). Such alterations include both reduced FC strengths

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