BACKGROUND 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. METHODS 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. RESULTS 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). CONCLUSIONS Collectively, the results provide evidence for persistent MDD effects across current episodes or remission, in the absence of detectable progressive neuropathology.

中文翻译：

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重度抑郁症发作和缓解的持续分子病理学

背景 重度抑郁症 (MDD) 是一种使人衰弱的精神疾病，并且是世界范围内生产力下降的主要原因。MDD 患者通常会终生反复发作，病情加重，治疗反应降低，缓解期更短，这表明存在持续的和潜在的进行性病理。方法 来自四个 MDD 队列（单次发作，n = 20；缓解中的单次发作，n = 15；复发发作，n = 20；缓解中的复发发作，n = 15）和一个对照队列的膝下前扣带回皮层死后样本(n = 20) 通过基于质谱的蛋白质组学 (n = 3630 蛋白质) 结合统计分析进行分析。使用无偏方法和先验假设检验对 MDD 中的特征和状态进行性神经病理学数据进行了调查。结果 数据为蛋白质组差异作为状态（抑郁/缓解）或先前发作次数的函数提供了微弱的证据。相反，它表明存在持续的 MDD 效应，无论发作或缓解状态如何，即与突触前神经传递、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质组学测量。选定的蛋白质（二氢嘧啶酶相关蛋白 1、突触体相关蛋白 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）通过蛋白质印迹分析进行验证。这些发现与技术、人口统计学（性别或年龄）或其他临床参数（自杀和药物治疗导致的死亡）无关。结论 总的来说，