Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Department of Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Psychol Med. 2024 Feb;54(3):582-591. doi: 10.1017/S0033291723002234. Epub 2023 Aug 9.
The age-related heterogeneity in major depressive disorder (MDD) has received significant attention. However, the neural mechanisms underlying such heterogeneity still need further investigation. This study aimed to explore the common and distinct functional brain abnormalities across different age groups of MDD patients from a large-sample, multicenter analysis.
The analyzed sample consisted of a total of 1238 individuals including 617 MDD patients (108 adolescents, 12-17 years old; 411 early-middle adults, 18-54 years old; and 98 late adults, > = 55 years old) and 621 demographically matched healthy controls (60 adolescents, 449 early-middle adults, and 112 late adults). MDD-related abnormalities in brain functional connectivity (FC) patterns were investigated in each age group separately and using the whole pooled sample, respectively.
We found shared FC reductions among the sensorimotor, visual, and auditory networks across all three age groups of MDD patients. Furthermore, adolescent patients uniquely exhibited increased sensorimotor-subcortical FC; early-middle adult patients uniquely exhibited decreased visual-subcortical FC; and late adult patients uniquely exhibited wide FC reductions within the subcortical, default-mode, cingulo-opercular, and attention networks. Analysis of covariance models using the whole pooled sample further revealed: (1) significant main effects of age group on FCs within most brain networks, suggesting that they are decreased with aging; and (2) a significant age group × MDD diagnosis interaction on FC within the default-mode network, which may be reflective of an accelerated aging-related decline in default-mode FCs.
To summarize, these findings may deepen our understanding of the age-related biological and clinical heterogeneity in MDD.
重度抑郁症（MDD）的年龄相关异质性受到了广泛关注。然而，这种异质性的神经机制仍需要进一步研究。本研究旨在通过大样本、多中心分析，探讨不同年龄组 MDD 患者共有的和独特的功能脑异常。
分析样本共包括 1238 人，其中 617 人为 MDD 患者（108 名青少年，12-17 岁；411 名中青年，18-54 岁；98 名老年，≥55 岁），621 名为年龄匹配的健康对照（60 名青少年，449 名中青年，112 名老年）。分别在每个年龄组和整个 pooled 样本中研究 MDD 相关的脑功能连接（FC）模式异常。
我们发现，所有三个年龄组的 MDD 患者的感觉运动、视觉和听觉网络之间存在共有的 FC 减少。此外，青少年患者表现出独特的感觉运动-皮质下 FC 增加；中青年患者表现出独特的视觉-皮质下 FC 减少；老年患者表现出皮质下、默认模式、扣带回-前运动网络和注意力网络内广泛的 FC 减少。使用整个 pooled 样本的协方差分析模型进一步显示：（1）FC 与年龄组之间存在显著的主效应，表明随着年龄的增长，FC 会减少；（2）默认模式网络中的 FC 存在年龄组×MDD 诊断的显著交互作用，这可能反映了默认模式 FC 与年龄相关的加速衰退。
总之，这些发现可能加深我们对 MDD 中与年龄相关的生物学和临床异质性的理解。
