Lamontagne Steven J, Gilbert Jessica R, Zabala Paloma K, Waldman Laura R, Zarate Carlos A, Ballard Elizabeth D
Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
Psychol Med. 2024 May;54(7):1431-1440. doi: 10.1017/S0033291723003331. Epub 2023 Nov 24.
An urgent need exists to identify neural correlates associated with differing levels of suicide risk and develop novel, rapid-acting therapeutics to modulate activity within these neural networks.
Electrophysiological correlates of suicide were evaluated using magnetoencephalography (MEG) in 75 adults with differing levels of suicide risk. During MEG scanning, participants completed a modified Life-Death Implicit Association Task. MEG data were source-localized in the gamma (30-58 Hz) frequency, a proxy measure of excitation-inhibition balance. Dynamic causal modeling was used to evaluate differences in connectivity estimates between risk groups. A proof-of-concept, open-label, pilot study of five high risk participants examined changes in gamma power after administration of ketamine (0.5 mg/kg), an NMDAR antagonist with rapid anti-suicide ideation effects.
Implicit self-associations with death were stronger in the highest suicide risk group relative to all other groups, which did not differ from each other. Higher gamma power for self-death compared to self-life associations was found in the orbitofrontal cortex for the highest risk group and the insula and posterior cingulate cortex for the lowest risk group. Connectivity estimates between these regions differentiated the highest risk group from the full sample. Implicit associations with death were not affected by ketamine, but enhanced gamma power was found for self-death associations in the left insula post-ketamine compared to baseline.
Differential implicit cognitive processing of life and death appears to be linked to suicide risk, highlighting the need for objective measures of suicidal states. Pharmacotherapies that modulate gamma activity, particularly in the insula, may help mitigate risk.Clinicaltrials.gov identifier: NCT02543983, NCT00397111.
迫切需要确定与不同自杀风险水平相关的神经关联，并开发新型速效疗法来调节这些神经网络内的活动。
使用脑磁图（MEG）对75名具有不同自杀风险水平的成年人进行自杀的电生理关联评估。在MEG扫描期间，参与者完成了一项改良的生死内隐联想任务。MEG数据在伽马（30 - 58赫兹）频率下进行源定位，这是兴奋 - 抑制平衡的一种替代测量方法。动态因果模型用于评估风险组之间连接性估计的差异。一项针对五名高风险参与者的概念验证、开放标签的试点研究，考察了给予氯胺酮（0.5毫克/千克）后伽马功率的变化，氯胺酮是一种具有快速抗自杀意念作用的NMDAR拮抗剂。
相对于所有其他组，最高自杀风险组中与死亡的内隐自我关联更强，而其他组之间没有差异。在最高风险组的眶额皮质以及最低风险组的岛叶和后扣带回皮质中，与自我生命关联相比，自我死亡的伽马功率更高。这些区域之间的连接性估计将最高风险组与整个样本区分开来。与死亡的内隐关联不受氯胺酮影响，但与基线相比，氯胺酮给药后左岛叶中自我死亡关联的伽马功率增强。
对生与死的不同内隐认知加工似乎与自杀风险相关，凸显了对自杀状态进行客观测量的必要性。调节伽马活动的药物疗法，特别是在岛叶，可能有助于降低风险。Clinicaltrials.gov标识符：NCT02543983，NCT00397111。
