Accelerated functional brain aging in major depressive disorder: evidence from a large scale fMRI analysis of Chinese participants

Abstract

Major depressive disorder (MDD) is one of the most common mental health conditions that has been intensively investigated for its association with brain atrophy and mortality. Recent studies suggest that the deviation between the predicted and the chronological age can be a marker of accelerated brain aging to characterize MDD. However, current conclusions are usually drawn based on structural MRI information collected from Caucasian participants. The universality of this biomarker needs to be further validated by subjects with different ethnic/racial backgrounds and by different types of data. Here we make use of the REST-meta-MDD, a large scale resting-state fMRI dataset collected from multiple cohort participants in China. We develop a stacking machine learning model based on 1101 healthy controls, which estimates a subject’s chronological age from fMRI with promising accuracy. The trained model is then applied to 1276 MDD patients from 24 sites. We observe that MDD patients exhibit a +4.43 years (p < 0.0001, Cohen’s d = 0.31, 95% CI: 2.23–3.88) higher brain-predicted age difference (brain-PAD) compared to controls. In the MDD subgroup, we observe a statistically significant +2.09 years (p < 0.05, Cohen’s d = 0.134525) brain-PAD in antidepressant users compared to medication-free patients. The statistical relationship observed is further checked by three different machine learning algorithms. The positive brain-PAD observed in participants in China confirms the presence of accelerated brain aging in MDD patients. The utilization of functional brain connectivity for age estimation verifies existing findings from a new dimension.

Sex-difference in the association between social drinking, structural brain aging and cognitive function in older individuals free of cognitive impairment

“…However, 98% of the participants are of Caucasian descent and they have relatively highly educated. Our cross-sectional study, despite an agreement with numerous cross-sectional brains aging studies ( 47 – 60 ) cannot make a definitive conclusion about accelerated aging and longitudinal studies are rather needed. In addition, more men, compared to women [58.1% (86/148) vs 51.2% 52/121)] reported alcohol drinking.…”

“…Premature, advanced, or accelerated brain aging are terms used to describe the gap between chronological age and estimated brain age derived from different machine learning algorithms. Accelerated brain aging is a non-specific observation that has been reported in many conditions such as major depression ( 47 – 50 ), psychosis ( 51 , 52 ), obsessive compulsive disorder ( 53 ), traumatic brain injury ( 54 , 55 ), tobacco smoking ( 56 ), diabetes mellitus ( 57 , 58 ), glioma patients following radiotherapy ( 59 ), and in healthy individuals with inadequate sleep ( 60 ). Few studies have reported negative association between accelerated brain aging and cognitive performance in patients with major psychoses ( 51 ), in older patients with depressive symptoms ( 61 ) and in patients with traumatic brain injury ( 54 ).…”

Classification of Major Depressive Disorder Based on Integrated Temporal and Spatial Functional MRI Variability Features of Dynamic Brain Network

“…18 It is a coordinated multisite project from China containing over 1000 MDD patients and normal controls and has been widely used by many studies. 8,19,20 In addition, we investigated the ability of altered spatiotemporal dynamics to assess MDD symptom severity.…”

“…We further tested the main results in a large MDD rs‐fMRI database, that is, REST‐meta‐MDD (http://rfmri.org/REST-meta-MDD). 18 It is a coordinated multisite project from China containing over 1000 MDD patients and normal controls and has been widely used by many studies 8,19,20 . In addition, we investigated the ability of altered spatiotemporal dynamics to assess MDD symptom severity.…”