Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Psychiatry and Psychotherapy, Campus Benjamin Franklin, Hindenburgdamm 30, 12203, Berlin, Germany; Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, BIH Biomedical Innovation Academy, Anna-Louisa-Karsch-Straße 2, 10178, Berlin, Germany.
Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Psychiatry and Psychotherapy, Campus Benjamin Franklin, Hindenburgdamm 30, 12203, Berlin, Germany.
J Psychiatr Res. 2022 Aug;152:97-103. doi: 10.1016/j.jpsychires.2022.06.016. Epub 2022 Jun 10.
Major depressive disorder (MDD) is associated with impairments in spatial learning and memory and with altered functioning of central mineralocorticoid receptors (MR) and glutamatergic N-methyl-D-aspartate receptors (NMDA-R). Both receptors are highly expressed in the hippocampus and prefrontal cortex - brain areas that are critical for spatial learning and memory. Here, we examined the effects of separate and combined MR and NMDA-R stimulation on spatial learning and memory in individuals with MDD and healthy controls.
We used a randomized, double-blind, placebo-controlled between-group study design to examine the effects of separate and combined stimulation of the MR (with 0.4 mg fludrocortisone) and NMDA-R (with 250 mg D-cycloserine) in 116 unmedicated individuals with MDD (mean age: 34.7 ± 13.3 years; 78.4% women) and 116 age-, sex-, and education-matched healthy controls. Participants were randomly assigned to one of four conditions: 1) placebo; 2) MR stimulation; 3) NMDA-R stimulation; and 4) combined MR/NMDA-R stimulation. Three hours after drug administration, spatial learning and memory were assessed using a virtual Morris Water Maze task.
Individuals with MDD and healthy controls did not differ in spatial learning and memory performance. Neither separate nor combined MR or NMDA-R stimulation altered measures of spatial performance.
In this study of relatively young, predominantly female, and unmedicated individuals, we found no effect of MDD and no effect of separate or combined MR and NMDA-R stimulation on spatial learning and memory.
重度抑郁症（MDD）与空间学习和记忆受损以及中枢盐皮质激素受体（MR）和谷氨酸 N-甲基-D-天冬氨酸受体（NMDA-R）功能改变有关。这两种受体在海马体和前额叶皮层中高度表达 - 这些区域对空间学习和记忆至关重要。在这里，我们研究了单独和联合刺激 MR（使用 0.4mg 氟氢可的松）和 NMDA-R（使用 250mg D-环丝氨酸）对 MDD 个体和健康对照者的空间学习和记忆的影响。
我们采用随机、双盲、安慰剂对照的分组研究设计，来研究 116 名未接受治疗的 MDD 患者（平均年龄：34.7±13.3 岁；78.4%为女性）和 116 名年龄、性别和教育程度匹配的健康对照者，分别接受 MR（0.4mg 氟氢可的松）和 NMDA-R（250mg D-环丝氨酸）单独和联合刺激的效果。参与者被随机分配到以下四个条件之一：1）安慰剂；2）MR 刺激；3）NMDA-R 刺激；4）MR/NMDA-R 联合刺激。给药后 3 小时，使用虚拟 Morris 水迷宫任务评估空间学习和记忆。
MDD 患者和健康对照组的空间学习和记忆表现没有差异。单独或联合刺激 MR 或 NMDA-R 均未改变空间表现的测量值。
在这项针对相对年轻、以女性为主、未接受治疗的个体的研究中，我们没有发现 MDD 的影响，也没有发现单独或联合刺激 MR 和 NMDA-R 对空间学习和记忆的影响。
