Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, Tennessee; Minneapolis Radiation Oncology, Edina, Minnesota.
Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, Tennessee; Department of Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Int J Radiat Oncol Biol Phys. 2022 Aug 1;113(5):960-966. doi: 10.1016/j.ijrobp.2022.04.042. Epub 2022 May 17.
Effective treatment options for refractory depression are needed. Recent advancements permit both precise ablative radiation and functional neurologic connectome analysis using standard magnetic resonance imaging. We combined these innovations to perform stereotactic radiosurgical capsulotomy for the treatment of medically refractory major depressive disorder and study connectome response using a novel tractography-based approach.
Patients with medically refractory depression were enrolled on a prospective pilot single-arm observational trial from 2020 to 2021 at a single academic tertiary referral center. Bilateral ablation of the anterior limb of the internal capsule was accomplished by mask-based linear accelerator stereotactic radiosurgery. Beck's Depression Inventory measured efficacy. Montreal Cognitive Assessment evaluated cognition.
Three patients were enrolled. Depression burden was improved by 88% at 12-month follow-up and by 55% at 18-month follow-up for patient 1 and 2, respectively. Patient 1 discontinued ketamine therapy, and patient 2 discontinued electroconvulsive therapy. Patient 3 reported global improvement in symptoms and function at 3 months. All 3 patients had reduction or resolution of suicidal ideation. No patient experienced cognitive decline or neurologic toxicity, and Montreal Cognitive Assessment score, as well as subjective patient-reported evaluations of concentration and attention, were superior after treatment. Tractography confirmed intended disruption of the cortico-striatal-thalamo-cortical loop with structural reorganization in the connectome. Connectome change was consistent between patients. Observed increases in caudate and putamen connectivity and decreases in thalamic connectivity may explain improved concentration, attention, and depression. The diversity and magnitude of connectome change may correlate with degree of clinical response.
In 3 patients with refractory depression, radiosurgical capsulotomy significantly reduced the burden of depression. Functional connectome reorganization offers neurobiological evidence to support further investigations of the role of radiosurgery in depression.
需要有效的难治性抑郁症治疗选择。最近的进展允许使用标准磁共振成像进行精确的消融性放射治疗和功能性神经连接组分析。我们结合这些创新技术，对 3 名药物难治性重度抑郁症患者进行了立体定向放射外科脑壳切开术治疗，并使用基于新型束追踪的方法研究了连接组的反应。
2020 年至 2021 年，在一家学术性三级转诊中心，对药物难治性抑郁症患者进行了前瞻性单臂观察性试验的前瞻性入组。通过基于面罩的直线加速器立体定向放射外科完成双侧内囊前肢消融。采用贝克抑郁量表评估疗效。蒙特利尔认知评估评估认知。
共入组 3 例患者。1 例和 2 例患者在 12 个月和 18 个月的随访中，抑郁负担分别改善了 88%和 55%。患者 1 停用了氯胺酮治疗，患者 2 停用了电抽搐治疗。患者 3 在 3 个月时报告症状和功能全面改善。所有 3 例患者的自杀意念均减少或消失。没有患者出现认知能力下降或神经毒性，治疗后蒙特利尔认知评估评分以及患者对注意力和注意力的主观评价均有所提高。束追踪证实了皮质-纹状体-丘脑-皮质回路的预期中断，并在连接组中发生了结构重组。患者之间的连接组变化一致。尾状核和壳核连接性增加和丘脑连接性降低可能解释了注意力、注意力和抑郁症状的改善。连接组变化的多样性和幅度可能与临床反应程度相关。
在 3 例难治性抑郁症患者中，放射外科脑壳切开术显著降低了抑郁负担。功能连接组重组提供了神经生物学证据，支持进一步研究放射外科在抑郁症中的作用。
