Romeo Zaira, Biondi Margherita, Oltedal Leif, Spironelli Chiara
Department of General Psychology, University of Padova, 35131 Padova, Italy.
Padova Neuroscience Center, University of Padova, 35131 Padova, Italy.
Depress Anxiety. 2024 Mar 2;2024:6673522. doi: 10.1155/2024/6673522. eCollection 2024.
While the brain correlates of major depressive disorder (MDD) have been extensively studied, there is no consensus conclusion so far. Various meta-analyses tried to determine the most consistent findings, but the results are often discordant for grey matter volume (GMV) atrophy and hypertrophy. Applying rigorous and stringent inclusion criteria and controlling for confounding factors, such as the presence of anxiety comorbidity, we carried out two novel meta-analyses on the existing literature to unveil MDD signatures.
A systematic literature search was performed up to January 2023. Seventy-three studies on MDD patients reporting GMV abnormalities were included in the first meta-analysis, for a total of 6167 patients and 6237 healthy controls (HC). To test the effects of anxiety comorbidity, we conducted a second meta-analysis, by adding to the original pure MDD sample a new cohort of MDD patients with comorbid anxiety disorders (308 patients and 342 HC). An activation likelihood estimation (ALE) analysis and a coordinate-based mapping approach separate for atrophy and hypertrophy were used to identify common brain structural alterations among patients.
The pure MDD sample exhibited atrophy in the left insula, as well as hypertrophy in the bilateral amygdala and parahippocampal gyri. When we added patients with comorbid anxiety to the original sample, bilateral insula atrophy emerged, whereas the hypertrophy results were not replicated.
Our findings revealed important structural alterations in pure MDD patients, particularly in the insula and amygdala, which play key roles in sensory input integration and in emotional processing, respectively. Additionally, the amygdala and parahippocampal gyrus hypertrophy may be related to MDD functional overactivation to emotional stimuli, rumination, and overactive self-referential thinking. Conversely, the presence of anxiety comorbidity revealed separate effects which were not seen in the pure MDD sample, underscoring the importance of strict inclusion criteria for investigations of disorder-specific effects.
虽然对重度抑郁症（MDD）的大脑相关性已进行了广泛研究，但迄今为止尚无共识性结论。各种荟萃分析试图确定最一致的研究结果，但关于灰质体积（GMV）萎缩和肥大的结果往往不一致。我们应用严格的纳入标准并控制混杂因素，如焦虑共病的存在，对现有文献进行了两项新颖的荟萃分析，以揭示MDD的特征。
截至2023年1月进行了系统的文献检索。第一项荟萃分析纳入了73项报告GMV异常的MDD患者研究，共有6167例患者和6237例健康对照（HC）。为了测试焦虑共病的影响，我们进行了第二项荟萃分析，在原始的单纯MDD样本中加入了一组新的伴有焦虑障碍的MDD患者队列（308例患者和342例HC）。使用激活可能性估计（ALE）分析和基于坐标的映射方法（分别针对萎缩和肥大）来识别患者之间常见的脑结构改变。
单纯MDD样本在左侧岛叶表现出萎缩，双侧杏仁核和海马旁回表现出肥大。当我们在原始样本中加入伴有焦虑的患者时，出现了双侧岛叶萎缩，而肥大结果未得到重复。
我们的研究结果揭示了单纯MDD患者重要的结构改变，特别是在岛叶和杏仁核，它们分别在感觉输入整合和情绪处理中起关键作用。此外，杏仁核和海马旁回肥大可能与MDD对情绪刺激、反刍和过度活跃的自我参照思维的功能过度激活有关。相反，焦虑共病的存在显示出在单纯MDD样本中未见的单独影响，强调了严格纳入标准对疾病特异性影响研究的重要性。
