Campbell Family Mental Health Research Institute of the Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada.
Department of Biostatistics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania.
Biol Psychiatry. 2018 Jan 1;83(1):81-89. doi: 10.1016/j.biopsych.2017.08.008. Epub 2017 Aug 18.
Major depressive disorder (MDD) is a debilitating mental illness and a major cause of lost productivity worldwide. MDD patients often suffer from lifelong recurring episodes of increasing severity, reduced therapeutic response, and shorter remission periods, suggesting the presence of a persistent and potentially progressive pathology.
Subgenual anterior cingulate cortex postmortem samples from four MDD cohorts (single episode, n = 20; single episode in remission, n = 15; recurrent episode, n = 20; and recurrent episode in remission, n = 15), and one control cohort (n = 20) were analyzed by mass spectrometry-based proteomics (n = 3630 proteins) combined with statistical analyses. The data was investigated for trait and state progressive neuropathologies in MDD using both unbiased approaches and tests of a priori hypotheses.
The data provided weak evidence for proteomic differences as a function of state (depressed/remitted) or number of previous episodes. Instead it suggested the presence of persistent MDD effects, regardless of episodes or remitted state, namely on proteomic measures related to presynaptic neurotransmission, synaptic function, cytoskeletal rearrangements, energy metabolism, phospholipid biosynthesis/metabolism, and calcium ion homeostasis. Selected proteins (dihydropyrimidinase-related protein 1, synaptosomal-associated protein 29, glutamate decarboxylase 1, metabotropic glutamate receptor 1, and excitatory amino acid transporter 3) were validated by Western blot analysis. The findings were independent of technical, demographic (sex or age), or other clinical parameters (death by suicide and drug treatment).
Collectively, the results provide evidence for persistent MDD effects across current episodes or remission, in the absence of detectable progressive neuropathology.
重度抑郁症（MDD）是一种使人衰弱的精神疾病，也是全球生产力下降的主要原因。MDD 患者常患有终生反复发作、治疗反应降低和缓解期缩短的情况，这表明存在持续且潜在进展性的病理。
通过基于质谱的蛋白质组学（n=3630 种蛋白质）联合统计学分析，对来自四个 MDD 队列（单发性发作，n=20；缓解期单发性发作，n=15；复发性发作，n=20；缓解期复发性发作，n=15）和一个对照组（n=20）的扣带回前部亚皮质下样本进行分析。使用无偏倚方法和先验假设检验，对 MDD 中的特征和状态进行神经病理学的进展性进行了数据调查。
数据提供了关于状态（抑郁/缓解）或先前发作次数的蛋白组差异的弱证据。相反，它表明存在持续的 MDD 效应，无论发作次数或缓解状态如何，即与突触前神经递质传递、突触功能、细胞骨架重排、能量代谢、磷脂生物合成/代谢和钙离子稳态相关的蛋白组测量值。通过 Western blot 分析验证了一些选定的蛋白质（二氢嘧啶酶相关蛋白 1、突触相关蛋白 29、谷氨酸脱羧酶 1、代谢型谷氨酸受体 1 和兴奋性氨基酸转运蛋白 3）。这些发现独立于技术、人口统计学（性别或年龄）或其他临床参数（自杀死亡和药物治疗）。
总的来说，这些结果提供了在没有可检测到的进行性神经病理学的情况下，MDD 对当前发作或缓解的持续影响的证据。
