Background: 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. Methods: 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). Results: 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 (p = 0.039) before
suvorexant treatment. There was no difference in the
N-acetylaspartate/
creatine and
phosphorylcreatine ratio (p = 0.297) between the two groups. Conclusions: 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.