The Abnormal N-Acetylaspartate to Creatine Ratio of the Right Putamen is Linked to Wakefulness in Patients with Insomnia Disorder

Converging evidence implicates the putamen in sleep-wake regulation. However, its role remains unclear. We hypothesized that metabolic abnormalities in the putamen are linked to insomnia disorder, which has not been previously addressed, and investigated putaminal N-acetylaspartate (NAA), choline (Cho), and creatine (Cr) in patients with insomnia disorder compared to healthy controls. In the present study, the concentrations of NAA, Cho, and Cr in the putamen of 23 patients with insomnia disorder and 18 healthy controls were determined using proton magnetic resonance spectroscopy. Sociodemographic, psychometric, and polysomnography data were obtained from all participants. We found that the mean NAA/Cr ratio of the right putamen was significantly greater in the insomnia group compared to the control group and also greater than the left putamen within the insomnia group. The NAA/Cr ratio of the right putamen distinguished insomnia disorder from normal sleep with 78.3% sensitivity and 61.1% specificity. Furthermore, this ratio positively correlated with both objective and subjective insomnia severity and sleep quality. Our findings provide critical evidence for the dysfunctional putaminal metabolism of NAA/Cr in insomnia disorder, suggesting that the abnormal NAA/Cr ratio of the right putamen is linked to wakefulness in patients with insomnia disorder and may serve as a potential biomarker of insomnia disorder.