Shan Zack Y, Can Adem T, Mohamed Abdalla Z, Dutton Megan, Hermens Daniel F, Calhoun Vince D, Williams Leanne M, Bennett Maxwell, Lagopoulos Jim
Thompson Institute, University of the Sunshine Coast, 12 Innovation Parkway, Birtinya, QLD, 4575, Australia.
Tri-institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State University, Georgia Institute of Technology, Emory University, Atlanta, GA, USA.
Eur Arch Psychiatry Clin Neurosci. 2024 May 21. doi: 10.1007/s00406-024-01831-x.
The underlying brain mechanisms of ketamine in treating chronic suicidality and the characteristics of patients who will benefit from ketamine treatment remain unclear. To address these gaps, we investigated temporal variations of brain functional synchronisation in patients with suicidality treated with ketamine in a 6-week open-label oral ketamine trial. The trial's primary endpoint was the Beck Scale for Suicide Ideation (BSS). Patients who experienced greater than 50% improvement in BSS scores or had a BSS score less than 6 at the post-treatment and follow-up (10 weeks) visits were considered responders and persistent responders, respectively. The reoccurring and transient connectivity pattern (termed brain state) from 29 patients (45.6 years ± 14.5, 15 females) were investigated by dynamic functional connectivity analysis of resting-state functional MRI at the baseline, post-treatment, and follow-up. Post-treatment patients showed significantly more (FDR-Q = 0.03) transitions among whole brain states than at baseline. We also observed increased dwelling time (FDR-Q = 0.04) and frequency (FDR-Q = 0.04) of highly synchronised brain state at follow-up, which were significantly correlated with BSS scores (both FDR-Q = 0.008). At baseline, persistent responders had higher fractions (FDR-Q = 0.03, Cohen's d = 1.39) of a cognitive control network state with high connectivities than non-responders. These findings suggested that ketamine enhanced brain changes among different synchronisation patterns and enabled high synchronisation patterns in the long term, providing a possible biological pathway for its suicide-prevention effects. Moreover, differences in cognitive control states at baseline may be used for precise ketamine treatment planning.
氯胺酮治疗慢性自杀倾向的潜在脑机制以及能从氯胺酮治疗中获益的患者特征仍不清楚。为填补这些空白，我们在一项为期6周的开放标签口服氯胺酮试验中，研究了接受氯胺酮治疗的自杀倾向患者脑功能同步性的时间变化。该试验的主要终点是贝克自杀意念量表（BSS）。在治疗后和随访（10周）时，BSS评分改善超过50%或BSS评分低于6的患者分别被视为反应者和持续反应者。通过对29名患者（45.6岁±14.5，15名女性）在基线、治疗后和随访时的静息态功能磁共振成像进行动态功能连接分析，研究了反复出现和短暂的连接模式（称为脑状态）。治疗后的患者全脑状态之间的转换显著多于基线时（FDR-Q = 0.03）。我们还观察到随访时高度同步脑状态的停留时间（FDR-Q = 0.04）和频率（FDR-Q = 0.04）增加，且与BSS评分显著相关（两者FDR-Q = 0.008）。在基线时，持续反应者具有高连接性的认知控制网络状态的比例高于无反应者（FDR-Q = 0.03，科恩d值 = 1.39）。这些发现表明，氯胺酮增强了不同同步模式之间的脑变化，并能长期实现高同步模式，为其预防自杀作用提供了一条可能的生物学途径。此外，基线时认知控制状态的差异可用于精确的氯胺酮治疗规划。
