Abstract：
Evidence has shown a rapid antidepressant and antisuicidal effects of low-dose ketamine infusion among patients with treatment-resistant depression (TRD) and prominent suicidal ideation (SI). The dorsolateral prefrontal cortex (DLPFC) plays a crucial role in the TRD pathomechanisms.
Whether the structural and functional changes of the DLPFC, particularly Brodmann area 46, are associated with the antidepressant and antisuicidal effects of ketamine infusion among such patients is unknown.
We randomized 48 patients with TRD and SI into groups receiving a single infusion of 0.5 mg/kg ketamine or 0.045 mg/kg midazolam. The Hamilton Depression Rating Scale and the Montgomery-Asberg Depression Rating Scale were used to assess symptoms. Positron emission tomography (PET)-magnetic resonance imaging was conducted prior to infusion and on Day 3 postinfusion. We performed longitudinal voxel-based morphometry (VBM) analysis to evaluate the gray matter (GM) volume changes of the DLPFC. The standardized uptake value ratio (SUVr) of 18F-fluorodeoxyglucose PET images was calculated using the SUV of the cerebellum as a reference region.
The VBM analysis revealed a small but significant volumetric reduction in the right DLPFC in the ketamine group compared with that in the midazolam group. A greater reduction in depressive symptoms was associated with a smaller decrease in right DLPFC volumes (p = 0.025). However, we found no SUVr changes of the DLPFC between baseline and post-Day 3 ketamine infusion.
The optimal modulation of the right DLPFC GM volumes may play an essential role in the antidepressant neuromechanisms of low-dose ketamine.
Whether the structural and functional changes of the DLPFC, particularly Brodmann area 46, are associated with the antidepressant and antisuicidal effects of ketamine infusion among such patients is unknown.
We randomized 48 patients with TRD and SI into groups receiving a single infusion of 0.5 mg/kg ketamine or 0.045 mg/kg midazolam. The Hamilton Depression Rating Scale and the Montgomery-Asberg Depression Rating Scale were used to assess symptoms. Positron emission tomography (PET)-magnetic resonance imaging was conducted prior to infusion and on Day 3 postinfusion. We performed longitudinal voxel-based morphometry (VBM) analysis to evaluate the gray matter (GM) volume changes of the DLPFC. The standardized uptake value ratio (SUVr) of 18F-fluorodeoxyglucose PET images was calculated using the SUV of the cerebellum as a reference region.
The VBM analysis revealed a small but significant volumetric reduction in the right DLPFC in the ketamine group compared with that in the midazolam group. A greater reduction in depressive symptoms was associated with a smaller decrease in right DLPFC volumes (p = 0.025). However, we found no SUVr changes of the DLPFC between baseline and post-Day 3 ketamine infusion.
The optimal modulation of the right DLPFC GM volumes may play an essential role in the antidepressant neuromechanisms of low-dose ketamine.
摘要：
背景：有证据表明，低剂量氯胺酮输注在难治性抑郁症（TRD）和明显自杀意念（SI）患者中具有快速的抗抑郁和抗自杀作用。背外侧前额叶皮层（DLPFC）在TRD发病机制中起着至关重要的作用。
目的：DLPFC的结构和功能是否发生变化，特别是Brodmann46区,在此类患者中与氯胺酮输注的抗抑郁和抗自杀作用相关,目前尚不清楚.
方法：我们将48例TRD和SI患者随机分为接受单次输注0.5mg/kg氯胺酮或0.045mg/kg咪达唑仑的组。汉密尔顿抑郁量表和蒙哥马利-阿斯伯格抑郁量表用于评估症状。在输注前和输注后第3天进行正电子发射断层摄影(PET)-磁共振成像。我们进行了基于纵向体素的形态测量（VBM）分析，以评估DLPFC的灰质（GM）体积变化。使用小脑的SUV作为参考区域来计算18F-氟代脱氧葡萄糖PET图像的标准化摄取值比率(SUVr)。
结果：VBM分析显示，与咪达唑仑组相比，氯胺酮组右侧DLPFC的体积减少很小但明显。抑郁症状的减少与右侧DLPFC体积的减少有关（p=0.025）。然而,我们没有发现基线和第3天氯胺酮输注后DLPFC的SUVr变化.
结论：正确的DLPFCGM体积的最佳调节可能在低剂量氯胺酮的抗抑郁神经机制中起重要作用。
目的：DLPFC的结构和功能是否发生变化，特别是Brodmann46区,在此类患者中与氯胺酮输注的抗抑郁和抗自杀作用相关,目前尚不清楚.
方法：我们将48例TRD和SI患者随机分为接受单次输注0.5mg/kg氯胺酮或0.045mg/kg咪达唑仑的组。汉密尔顿抑郁量表和蒙哥马利-阿斯伯格抑郁量表用于评估症状。在输注前和输注后第3天进行正电子发射断层摄影(PET)-磁共振成像。我们进行了基于纵向体素的形态测量（VBM）分析，以评估DLPFC的灰质（GM）体积变化。使用小脑的SUV作为参考区域来计算18F-氟代脱氧葡萄糖PET图像的标准化摄取值比率(SUVr)。
结果：VBM分析显示，与咪达唑仑组相比，氯胺酮组右侧DLPFC的体积减少很小但明显。抑郁症状的减少与右侧DLPFC体积的减少有关（p=0.025）。然而,我们没有发现基线和第3天氯胺酮输注后DLPFC的SUVr变化.
结论：正确的DLPFCGM体积的最佳调节可能在低剂量氯胺酮的抗抑郁神经机制中起重要作用。
