Department of Neurosurgery, Center for Functional Neurosurgery, Clinical Neuroscience Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shanghai Center for Brain Science and Brain-inspired Technology, Shanghai, China.
Transl Psychiatry. 2022 Feb 3;12(1):52. doi: 10.1038/s41398-022-01818-z.
Deep brain stimulation (DBS) of structures in the brain's reward system is a promising therapeutic option for patients with treatment-resistant depression (TRD). Recently, DBS of the habenula (HB) in the brain's anti-reward system has also been reported to alleviate depressive symptoms in patients with TRD or bipolar disorder (BD). In this pilot open-label prospective study, we explored the safety and clinical effectiveness of HB-DBS treatment in seven patients with TRD or BD. Also, local field potentials (LFPs) were recorded from the patients' left and right HB to explore the power and asymmetry of oscillatory activities as putative biomarkers of the underlying disease state. At 1-month follow-up (FU), depression and anxiety symptoms were both reduced by 49% (n = 7) along with substantial improvements in patients' health status, functional impairment, and quality of life. Although the dropout rate was high and large variability in clinical response existed, clinical improvements were generally maintained throughout the study [56%, 46%, and 64% reduction for depression and 61%, 48%, and 70% reduction for anxiety at 3-month FU (n = 5), 6-month FU (n = 5), and 12-month FU (n = 3), respectively]. After HB-DBS surgery, sustained improvements in mania symptoms were found in two patients who presented with mild hypomania at baseline. Another patient, however, experienced an acute manic episode 2 months after surgery that required hospitalization. Additionally, weaker and more symmetrical HB LFP oscillatory activities were associated with more severe depression and anxiety symptoms at baseline, in keeping with the hypothesis that HB dysfunction contributes to MDD pathophysiology. These preliminary findings indicate that HB-DBS may offer a valuable treatment option for depressive symptoms in patients who suffer from TRD or BD. Larger and well-controlled studies are warranted to examine the safety and efficacy of HB-DBS for treatment-refractory mood disorders in a more rigorous fashion.
脑深部电刺激（DBS）对大脑奖励系统结构的刺激是治疗难治性抑郁症（TRD）患者的一种很有前途的治疗选择。最近，大脑抗奖励系统的缰核（HB）的 DBS 也被报道可以缓解 TRD 或双相障碍（BD）患者的抑郁症状。在这项初步的开放性前瞻性研究中，我们探讨了 HB-DBS 治疗 7 例 TRD 或 BD 患者的安全性和临床疗效。此外，还从患者的左、右 HB 记录局部场电位（LFPs），以探索振荡活动的功率和不对称性作为潜在疾病状态的生物标志物。在 1 个月的随访（FU）时，7 名患者的抑郁和焦虑症状均减轻了 49%（n=7），同时患者的健康状况、功能障碍和生活质量也有了实质性的改善。尽管脱落率较高，临床反应的变异性较大，但临床改善在整个研究过程中基本保持不变[3 个月 FU（n=5）时抑郁减轻 56%、46%和 64%，焦虑减轻 61%、48%和 70%；5 个月 6 个月 FU（n=5）时抑郁减轻 56%、46%和 64%，焦虑减轻 61%、48%和 70%；3 个月 FU（n=3）时抑郁减轻 56%、46%和 64%，焦虑减轻 61%、48%和 70%]。HB-DBS 手术后，两名基线时轻度轻躁狂的患者发现躁狂症状持续改善。然而，另一名患者在手术后 2 个月时出现急性躁狂发作，需要住院治疗。此外，HB LFPs 振荡活动的强度较弱且更对称与基线时更严重的抑郁和焦虑症状相关，这与 HB 功能障碍导致 MDD 病理生理学的假设一致。这些初步发现表明，HB-DBS 可能为 TRD 或 BD 患者的抑郁症状提供一种有价值的治疗选择。需要更大规模和更好控制的研究，以更严格的方式检查 HB-DBS 治疗难治性心境障碍的安全性和疗效。
