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 age-differentiated 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.