Izuhara Muneto, Miura Shoko, Otsuki Koji, Nagahama Michiharu, Hayashida Maiko, Hashioka Sadayuki, Asou Hiroya, Kitagaki Hajime, Inagaki Masatoshi
Department of Clinical Laboratory, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan.
Department of Sleep-Wake Disorders, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan.
Front Psychiatry. 2021 Aug 23;12:714376. doi: 10.3389/fpsyt.2021.714376. eCollection 2021.
The ventral tegmental area (VTA; a dopaminergic nucleus) plays an important role in the sleep-wake regulation system including orexin system. In addition to neuronal activity, there is increasing evidence for an important role of glial cells (i.e., astrocytes and microglia) in these systems. The present study examined the utility of magnetic resonance spectroscopy (MRS) for detecting neural and/or glial changes in the VTA to distinguish responders from non-responders before treatment with the orexin receptor antagonist suvorexant. A total of 50 patients were screened and 9 patients were excluded. The remaining 41 patients with insomnia who have or not a psychiatric disease who were expected to receive suvorexant treatment were included in this study. We compared MRS signals in the VTA between responders to suvorexant and non-responders before suvorexant use. Based on previous reports, suvorexant responders were defined as patients who improved ≥3 points on the Pittsburgh Sleep Quality Index after 4 weeks of suvorexant use. MRS data included choline (reflects non-specific cell membrane breakdown, including of glial cells) and N-acetylaspartate (a decrease reflects neuronal degeneration). Among 41 examined patients, 20 patients responded to suvorexant and 21 patients did not. By MRS, the choline/creatine and phosphorylcreatine ratio in the VTA was significantly high in non-responders compared with responders ( = 0.039) before suvorexant treatment. There was no difference in the N-acetylaspartate/creatine and phosphorylcreatine ratio ( = 0.297) between the two groups. Changes in glial viability in the VTA might be used to distinguish responders to suvorexant from non-responders before starting treatment. These findings may help with more appropriate selection of patients for suvorexant treatment in clinical practice. Further, we provide novel possible evidence for a relationship between glial changes in the VTA and the orexin system, which may aid in the development of new hypnotics focusing on the VTA and/or glial cells.
腹侧被盖区（VTA；一个多巴胺能核团）在包括食欲素系统在内的睡眠-觉醒调节系统中发挥着重要作用。除了神经元活动外，越来越多的证据表明神经胶质细胞（即星形胶质细胞和小胶质细胞）在这些系统中也起着重要作用。本研究检测了磁共振波谱（MRS）用于检测VTA中神经和/或胶质细胞变化以区分食欲素受体拮抗剂苏沃雷生治疗前的反应者和无反应者的效用。共筛查了50例患者，排除9例。本研究纳入了其余41例有或无精神疾病且预期接受苏沃雷生治疗的失眠患者。我们比较了苏沃雷生反应者和无反应者在使用苏沃雷生前VTA中的MRS信号。根据先前的报告，苏沃雷生反应者被定义为使用苏沃雷生4周后匹兹堡睡眠质量指数改善≥3分的患者。MRS数据包括胆碱（反映非特异性细胞膜分解，包括神经胶质细胞的分解）和N-乙酰天门冬氨酸（其减少反映神经元变性）。在41例接受检查的患者中，20例对苏沃雷生有反应，21例无反应。通过MRS检测，在使用苏沃雷生治疗前，无反应者VTA中的胆碱/肌酸和磷酸肌酸比值显著高于反应者（P = 0.039）。两组之间的N-乙酰天门冬氨酸/肌酸和磷酸肌酸比值无差异（P = 0.297）。VTA中神经胶质细胞活力的变化可能用于在开始治疗前区分苏沃雷生的反应者和无反应者。这些发现可能有助于在临床实践中更恰当地选择接受苏沃雷生治疗的患者。此外，我们为VTA中的神经胶质细胞变化与食欲素系统之间的关系提供了新的可能证据，这可能有助于开发针对VTA和/或神经胶质细胞的新型催眠药。
