Yang Li, Wei An-Hai, Ouyang Tan-Te, Cao Zhen-Zhen, Duan Ao-Wen, Zhang He-Hua
Department of Medical Engineering, Daping Hospital, Army Medical University, Chongqing, China.
College of Communication Engineering of Chongqing University, Chongqing, China.
Ann Transl Med. 2021 Feb;9(4):349. doi: 10.21037/atm-21-367.
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.
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 HC) was conducted in each age group and Granger causal analysis (GCA) was applied to investigate effective connectivity between regions.
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.
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.
抑郁症的神经发育和神经退行性理论表明，重度抑郁症（MDD）患者可能遵循异常的发育、成熟和衰老过程。然而，缺乏寿命研究妨碍了对这些理论的验证。在此，我们分析了功能磁共振成像（fMRI）数据，以全面表征MDD病程中与年龄相关的功能轨迹，该轨迹通过低频波动分数振幅（fALFF）来衡量。
本研究共纳入235例发病年龄有差异的MDD患者和235例年龄及性别匹配的健康对照（HC）。我们通过在整个寿命期间横断面建立fALFF与年龄之间的一般线性模型（GLM），确定了与年龄相关的fALFF变化模式。此外，将受试者分为四个年龄组，以详细评估与年龄相关的神经变化。在每个年龄组中进行组间fALFF比较（MDD与HC），并应用格兰杰因果分析（GCA）来研究区域之间的有效连接性。
与HC相比，在整个寿命期间，MDD中未发现显著的二次或线性年龄效应，这表明抑郁症会影响正常的发育、成熟和退化过程。fALFF值的组间差异在不同发病年龄时显著不同。这意味着MDD可能以高度动态的方式影响脑功能，在生命的不同阶段有不同的改变模式。此外，GCA分析结果表明，MDD相对于HC遵循一种独特的有效连接模式，这可能是不同发病年龄的MDD的神经基础。
我们的研究结果提供了证据，表明正常的发育、成熟和衰老过程受到MDD的影响。最显著的是，不同发病年龄的MDD中的功能可塑性变化以特定脑区的方式涉及神经病理过程之间的动态相互作用。
