Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas, USA.
Department of Neuroscience, Baylor College of Medicine, Houston, Texas, USA.
Int J Neuropsychopharmacol. 2021 May 18;24(5):383-391. doi: 10.1093/ijnp/pyaa089.
Ketamine's potent and rapid antidepressant properties have shown great promise to treat severe forms of major depressive disorder (MDD). A recently hypothesized antidepressant mechanism of action of ketamine is the inhibition of N-methyl-D-aspartate receptor-dependent bursting activity of the habenula (Hb), a small brain structure that modulates reward and affective states.
Resting-state functional magnetic resonance imaging was conducted in 35 patients with MDD at baseline and 24 hours following treatment with i.v. ketamine. A seed-to-voxel functional connectivity (FC) analysis was performed with the Hb as a seed-of-interest. Pre-post changes in FC and the associations between changes in FC of the Hb and depressive symptom severity were examined.
A reduction in Montgomery-Åsberg Depression Rating Scale scores from baseline to 24 hours after ketamine infusion was associated with increased FC between the right Hb and a cluster in the right frontal pole (t = 4.65, P = .03, false discovery rate [FDR]-corrected). A reduction in Quick Inventory of Depressive Symptomatology-Self Report score following ketamine was associated with increased FC between the right Hb and clusters in the right occipital pole (t = 5.18, P < .0001, FDR-corrected), right temporal pole (t = 4.97, P < .0001, FDR-corrected), right parahippocampal gyrus (t = 5.80, P = .001, FDR-corrected), and left lateral occipital cortex (t = 4.73, P = .03, FDR-corrected). Given the small size of the Hb, it is possible that peri-habenular regions contributed to the results.
These preliminary results suggest that the Hb might be involved in ketamine's antidepressant action in patients with MDD, although these findings are limited by the lack of a control group.
氯胺酮具有强大而快速的抗抑郁作用，有望治疗重度抑郁症（MDD）。氯胺酮最近提出的一种抗抑郁作用机制是抑制 N-甲基-D-天冬氨酸受体依赖性缰核（Hb）爆发活动，Hb 是调节奖赏和情感状态的一个小的脑结构。
在基线时和静脉注射氯胺酮治疗后 24 小时对 35 例 MDD 患者进行静息态功能磁共振成像。使用 Hb 作为感兴趣区进行种子到体素功能连接（FC）分析。检查 FC 的前后变化以及 Hb 的 FC 变化与抑郁症状严重程度之间的相关性。
与氯胺酮输注后 24 小时相比，蒙哥马利-阿斯伯格抑郁评定量表（MADRS）评分的降低与右侧 Hb 与右侧额极内一个簇之间的 FC 增加有关（t=4.65，P=0.03，经 FDR 校正）。氯胺酮治疗后，快速抑郁症状自评量表（QIDS-SR）评分降低与右侧 Hb 与右侧枕极内簇（t=5.18，P<0.0001，经 FDR 校正）、右侧颞极（t=4.97，P<0.0001，经 FDR 校正）、右侧海马旁回（t=5.80，P=0.001，经 FDR 校正）和左侧外侧枕叶皮层（t=4.73，P=0.03，经 FDR 校正）之间的 FC 增加有关。鉴于 Hb 的体积较小，peri-habenular 区域可能对结果有贡献。
这些初步结果表明，Hb 可能参与了 MDD 患者氯胺酮的抗抑郁作用，尽管这些发现受到缺乏对照组的限制。
