Sarasso Pietro, Billeci Martina, Ronga Irene, Raffone Fabiola, Martiadis Vassilis, Di Petta Gilberto
Brain Plasticity and Behaviour Changes Research Group, Department of Psychology, University of Turin, Turin, Italy.
SPDC, Mental Health Department, Santa Maria delle Grazie Hospital, ASL 2, Naples, Italy.
Psychopathology. 2024;57(6):480-491. doi: 10.1159/000539714. Epub 2024 Aug 22.
Dissociative experiences are considered undesirable ketamine's adverse events. However, they might be crucial for ketamine's antidepressant effects, at least in some depression subtypes. Current understandings of ketamine's therapeutic potentials converge on the so-called "relaxed prior hypothesis," suggesting that glutamatergic blockage up-weights bottom-up surprising somatosensory/affective states. As a result, ketamine improves short-term plasticity in depression by enhancing sensitivity to interoceptive signals.
We selected 2 case studies for their paradigmatic description of "depersonalized depression" (Entfremdungsdepression) symptoms. Patients were included in a 6-month-long esketamine program for treatment resistant depression, during which we collected their spontaneous experience with esketamine. According to a neurophenomenological approach, we combined subjective reports from unstructured clinical interviews and the review of previous objective neuroimaging results and neurocomputational models to unveil the relation between esketamine antidepressant effects and interoceptive sensitivity.
According to our clinical observations, esketamine-induced dissociation might be particularly effective in the depersonalized depression subtype, in which interoceptive awareness and interaffectivity are particularly compromised. Ketamine and esketamine's dissociative effects and particularly disembodiment might suspend previously acquired patterns of feeling, sensing, and behaving.
Coherently with previous research, we suggest that esketamine-induced disembodiment allows for a transient window of psychological plasticity and enhanced sensitivity, where the body recovers its permeability to affective affordances.
解离体验被认为是氯胺酮不良事件中不受欢迎的部分。然而，它们可能对氯胺酮的抗抑郁作用至关重要，至少在某些抑郁症亚型中如此。目前对氯胺酮治疗潜力的理解集中在所谓的“放松先验假设”上，该假设表明谷氨酸能阻滞增强了自下而上的令人惊讶的体感/情感状态。因此，氯胺酮通过增强对内感受信号的敏感性来改善抑郁症中的短期可塑性。
我们选择了2个案例研究，因其对“人格解体性抑郁症”症状的典型描述。患者被纳入为期6个月的艾司氯胺酮治疗难治性抑郁症项目，在此期间我们收集了他们使用艾司氯胺酮的自发体验。根据神经现象学方法，我们将非结构化临床访谈的主观报告与对先前客观神经影像学结果和神经计算模型的回顾相结合，以揭示艾司氯胺酮抗抑郁作用与内感受敏感性之间的关系。
根据我们的临床观察，艾司氯胺酮引起的解离在人格解体性抑郁症亚型中可能特别有效，在该亚型中内感受意识和相互情感性受到特别损害。氯胺酮和艾司氯胺酮的解离作用，特别是去身体化，可能会暂停先前习得的感觉、感知和行为模式。
与先前的研究一致，我们认为艾司氯胺酮引起的去身体化允许一个短暂的心理可塑性和增强敏感性的窗口，在此期间身体恢复其对情感可供性的通透性。
