1Department of Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai.
2Center for Functional Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai.
J Neurosurg. 2024 Jan 12;140(6):1630-1640. doi: 10.3171/2023.10.JNS231855. Print 2024 Jun 1.
Treatment-resistant depression (TRD) is a severely disabling psychiatric condition that responds poorly to conventional treatments. Deep brain stimulation (DBS) has been proposed for the treatment of patients with TRD in numerous studies. Several deep brain nuclei are considered as potential targets for TRD-DBS, but their clinical efficacy needs further validation. This study carried out dual-target combined stimulation of the bed nucleus of the stria terminalis (BNST) and nucleus accumbens (NAc) to investigate the effectiveness of the treatment for TRD patients.
An 8-contact DBS electrode was used in the study with a surgical path that crossed the BNST and NAc targets. Stimulation parameters and the corresponding severity of symptoms evaluated by the 17-item Hamilton Depression Rating Scale (HAMD-17) and other scales were obtained at each follow-up. The accuracy of electrode positions, the effect of combined stimulation, and the corresponding stimulation parameters were evaluated. Sweet spot prediction models were used to assess the effective stimulation sites in the treatment.
The study included 23 TRD patients undergoing DBS at a single center from March 2021 to May 2023. At the last follow-up (range 4-24 months), 14 patients had responded to the treatment (HAMD-17 score improved ≥ 50%), 7 of whom had achieved clinical remission (HAMD-17 score ≤ 7). Electrode position analysis suggested that the BNST may be more important for the improvement of depressive symptoms than the NAc. Overlapped volumes of volume of tissue activated (VTA) and BNST were significantly correlated with absolute (ρleft = -0.377, p < 0.001; ρright = -0.251, p < 0.001) and percent (ρleft = -0.249, p < 0.001; ρright = -0.098, p = 0.102) changes in HAMD-17 score. The sweet spot model of HAMD-17 improvement also suggested that the VTA overlap with the dorsal side of BNST was associated with the impact on depressive symptoms (t = -4.10, p < 0.05).
Combined BNST-NAc stimulation of TRD can effectively improve depressive symptoms, in which the BNST seems to have a dominant therapeutic effect. The results of this study not only help to optimize the DBS programming parameters, but also offer an opportunity to further understand the differences between the two targets. In the future, larger prospective cohorts are needed to verify the results of combined BNST-NAc DBS.
治疗抵抗性抑郁症（TRD）是一种严重致残的精神疾病，对常规治疗反应不佳。许多研究提出了深部脑刺激（DBS）治疗 TRD 患者。有几个深部脑核被认为是 TRD-DBS 的潜在靶点，但它们的临床疗效需要进一步验证。本研究对终纹床核（BNST）和伏隔核（NAc）进行双靶点联合刺激，以研究治疗 TRD 患者的效果。
研究采用 8 触点 DBS 电极，手术路径穿过 BNST 和 NAc 靶点。在每次随访时，通过 17 项汉密尔顿抑郁评定量表（HAMD-17）和其他量表评估症状严重程度和刺激参数。评估电极位置的准确性、联合刺激的效果和相应的刺激参数。使用“甜区”预测模型来评估治疗中的有效刺激部位。
本研究纳入了 2021 年 3 月至 2023 年 5 月在单中心接受 DBS 治疗的 23 例 TRD 患者。在最后一次随访（4-24 个月）时，14 例患者的治疗有反应（HAMD-17 评分改善≥50%），其中 7 例达到临床缓解（HAMD-17 评分≤7）。电极位置分析表明，BNST 对改善抑郁症状可能比 NAc 更重要。激活组织体积（VTA）和 BNST 的重叠体积与 HAMD-17 评分的绝对值（ρleft = -0.377，p < 0.001；ρright = -0.251，p < 0.001）和百分比（ρleft = -0.249，p < 0.001；ρright = -0.098，p = 0.102）变化显著相关。HAMD-17 改善的“甜区”模型也表明，VTA 与 BNST 背侧的重叠与对抑郁症状的影响有关（t = -4.10，p < 0.05）。
TRD 的 BNST-NAc 联合刺激可以有效改善抑郁症状，其中 BNST 似乎具有主导的治疗效果。本研究结果不仅有助于优化 DBS 编程参数，还有机会进一步了解两个靶点之间的差异。未来需要更大的前瞻性队列来验证 BNST-NAc DBS 的联合效果。
