[Correlations of calmodulin and neurotransmitters with polysomnographic parameters in patients with chronic insomnia...

Chronic insomnia disorder (CID) is a common sleep disorder that can cause a variety of health problems. Neurotransmitters, particularly gamma-aminobutyric acid (GABA), glutamate (Glu), and 5-hydroxytryptamine (5-HT), play key roles in sleep regulation, and calmodulin (CaM) is involved in their regulatory processes. However, systematic studies examining the correlations of CaM and related neurotransmitter levels with polysomnographic (PSG) parameters are currently lacking, and the diagnostic value of these indicators for CID remains unclear. This study aims to compare biochemical indicators between patients with CID and healthy controls (HCs), analyze their correlations with PSG parameters, and evaluate their diagnostic performance for CID, with the goal of identifying novel blood biomarkers for the auxiliary diagnosis of CID and exploring their potential clinical applications.

A total of 103 patients with CID who attended the Department of Neurology of the Second Affiliated Hospital of University of South China between January 2017 and April 2019 and 102 HCs who underwent health examinations during the same period were enrolled. Serum levels of CaM, GABA, Glu, and 5-HT were measured by enzyme-linked immunosorbent assay (ELISA) and compared between the 2 groups. Correlations between these indicators and PSG parameters were analyzed, and receiver operating characteristic (ROC) curves were generated to evaluate their diagnostic performance.

Compared with the HC group, the CID group had significantly lower serum CaM, GABA, and 5-HT levels and ratio of GABA to Glu (GABA/Glu), but significantly higher Glu levels (all P<0.05). In the CID group, the serum GABA/Glu was positively correlated with N3 sleep duration (r=0.225, P=0.022), and serum 5-HT levels were positively correlated with sleep efficiency (r=0.215, P=0.029). The areas under the curve (AUCs) for serum CaM, the GABA/Glu, and 5-HT in diagnosing CID were 0.616, 0.609, and 0.790, respectively (all P<0.05). Among these indicators, 5-HT demonstrated the best diagnostic performance, with an AUC of 0.790. At a serum 5-HT cutoff value of less than 125.249 ng/mL, the diagnostic accuracy for CID was 79.0%. A combined diagnostic model constructed using Logistic regression based on these 3 indicators significantly improved diagnostic performance, yielding an AUC of 0.800 [95% confidence interval (CI) 0.739 to 0.861], a sensitivity of 81.4%, and a specificity of 68.0% (P<0.01).

Patients with CID had significantly lower serum CaM, GABA, and 5-HT levels and GABA/Glu and significantly higher Glu levels. In patients with CID, the serum GABA/Glu was positively correlated with N3 sleep duration, whereas the serum 5-HT level was positively correlated with sleep efficiency. Serum CaM, the GABA/Glu, and 5-HT have diagnostic value for CID, and a combined diagnostic model incorporating all 3 indicators has better diagnostic performance than any individual indicator.