Functional plasticity abnormalities over the lifespan of first-episode patients with major depressive disorder: a resting state fMRI study

Abstract

Background: Neurodevelopmental and neurodegenerative theories of depression suggest that patients with major depressive disorder (MDD) may follow abnormal developmental, maturational, and aging processes.However, a lack of lifespan studies has precluded verification of these theories. Herein, we analyzed functional magnetic resonance imaging (fMRI) data to comprehensively characterize age-related functional trajectories, as measured by the fractional amplitude of low frequency fluctuations (fALFF), over the course of MDD.Methods: In total, 235 MDD patients with age-differentiated onsets and 235 age-and sex-matched healthy controls (HC) were included in this study. We determined the pattern of age-related fALFF changes by cross-sectionally establishing the general linear model (GLM) between fALFF and age over a lifespan. Furthermore, the subjects were divided into four age groups to assess age-related neural changes in detail.Inter-group fALFF comparison (MDD vs. HC) was conducted in each age group and Granger causal analysis (GCA) was applied to investigate effective connectivity between regions.Results: Compared with the HC, no significant quadratic or linear age effects were found in MDD over the entire lifespan, suggesting that depression affects the normal developmental, maturational, and degenerative process. Inter-group differences in fALFF values varied significantly at different ages of onset. This implies that MDD may impact brain functions in a highly dynamic way, with different patterns of alterations at different stages of life. Moreover, the GCA analysis results indicated that MDD followed a distinct pattern of effective connectivity relative to HC, and this may be the neural basis of MDD with agedifferentiated onsets.Conclusions: Our findings provide evidence that normal developmental, maturational, and ageing processes were affected by MDD. Most strikingly, functional plasticity changes in MDD with different ages of onset involved dynamic interactions between neuropathological processes in a tract-specific manner.

The thalamus is the causal hub of intervention in patients with major depressive disorder: Evidence from the Granger causality analysis

“…Two studies investigated the abnormal connection patterns between MDD patients and patients with amnestic mild cognitive impairment disease or Parkinson’s disease, which lacked results compared with normal controls ( Liang et al, 2016 , Zheng et al, 2017 ). The study of Yang et al only reported the connectivities that had changed but did not indicate whether the changes were enhanced or weakened ( Yang et al, 2021a ).…”

“…In recent years, the GC approach has been widely used to investigate the intrinsic effective connectivity (EC) network in resting-state functional magnetic resonance imaging (rs-fMRI) data ( Bi et al, 2019 , Iwabuchi et al, 2017 , Jiang et al, 2017 ). The alteration of EC networks in MDD patients is viewed as an important aspect of pathogenesis and potential intervention targets of MDD ( Feng et al, 2016 , Hamilton et al, 2011 , Yang et al, 2021a ).…”

Altered Brain Function and Causal Connectivity Induced by Repetitive Transcranial Magnetic Stimulation Treatment for Major Depressive Disorder

“…Granger causality analysis (GCA) is a method used for identifying the effective connectivity of the directed functional interactions from time-series data, and it has been widely used in resting-state fMRI studies ( Berlim et al, 2014 ; Gaynes et al, 2014 ; Yang et al, 2021 ). Feng et al (2016) analyzed the data of 23 drug-naive patients with first-onset MDD using GCA.…”