BACKGROUND Glutamate, an excitatory neurotransmitter binding to three classes of receptors including the N-methyl, D-aspartate (NMDA) receptor. NMDA receptor binding is lower in major depression (MDD) and suicide. NMDA receptor blocking with ketamine can have antidepressant and anti-suicide effects. Early life adversity (ELA) may cause glutamate mediated excitotoxicity, and is more common with MDD and in suicide decedents. We sought to determine whether NMDA-receptor binding is altered with suicide and ELA. METHODS 52 postmortem cases were organized as 13 quadruplets of suicide and non-suicide decedents matched for age, sex, and PMI, with or without reported ELA (< 16 years). Tissue blocks containing dorsal prefrontal (BA8), dorsolateral prefrontal (BA9) or anterior cingulate (BA24) cortex were collected at autopsy. Psychiatrically healthy controls and suicide decedents underwent psychological autopsy to determine psychiatric diagnoses and details of childhood adversity. NMDA receptor binding was determined by quantitative autoradiography of [3H]MK-801 binding (displaced by unlabeled MK-801) in 20 µm-thick sections. RESULTS [3H]MK-801 binding was not associated with suicide in BA8, BA9 or BA24. However, [3H]MK-801 binding with ELA was less in BA8, BA9 and BA24 independent of suicide (p<0.05). [3H]MK-801 binding was not associated with age or PMI in any brain region or group. CONCLUSIONS Less NMDA receptor binding with ELA is consistent with the hypothesis that stress can cause excitotoxicity via excessive glutamate causing either NMDA receptor downregulation or less receptor binding due to neuron loss consequent to the excitotoxicity.

中文翻译：

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背外侧前额叶皮层和前扣带皮层中 NMDA 受体结合较少，与报告的早期生活逆境有关，但与自杀无关。

背景谷氨酸，一种与三类受体结合的兴奋性神经递质，包括N-甲基、D-天冬氨酸(NMDA)受体。NMDA 受体结合在重度抑郁症 (MDD) 和自杀中较低。用氯胺酮阻断 NMDA 受体可具有抗抑郁和抗自杀作用。早期生活逆境 (ELA) 可能导致谷氨酸介导的兴奋性毒性，并且在 MDD 和自杀死者中更常见。我们试图确定 NMDA 受体结合是否因自杀和 ELA 而改变。方法 将 52 例死后病例组织为 13 组在年龄、性别和 PMI 上匹配的自杀和非自杀死者，无论是否报告 ELA（<16 岁）。在尸检时收集含有背前额叶 (BA8)、背外侧前额叶 (BA9) 或前扣带回 (BA24) 皮质的组织块。精神健康的对照者和自杀死亡者接受了心理尸检，以确定精神病学诊断和童年逆境的细节。NMDA 受体结合是通过 [3H]MK-801 结合（被未标记的 MK-801 取代）在 20 µm 厚切片中的定量放射自显影确定的。结果 [3H]MK-801 结合与 BA8、BA9 或 BA24 中的自杀无关。然而，[3H]MK-801 与 ELA 的结合在 BA8、BA9 和 BA24 中较少，与自杀无关（p<0.05）。[3H]MK-801 结合与任何大脑区域或组的年龄或 PMI 无关。结论 较少的 NMDA 受体与 ELA 结合与压力可通过过量谷氨酸引起兴奋性毒性的假设一致，导致 NMDA 受体下调或由于兴奋性毒性导致的神经元丢失导致受体结合减少。