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Peer-reviewedCC BY-NCNeuropsychiatric disease and treatment

Peripheral GRM2 and GRM3 mRNA Alterations and Clinical Correlates in Insomnia Disorder: A Case-Control Pilot Study.

4 affiliations
  1. 1Department of Psychiatry, The First Affiliated Hospital of Jinan University, Guangzhou, 510632, People's Republic of China.
  2. 2Department of Psychiatry, The Third Affiliated Hospital, Southern Medical University, Guangzhou, 510630, People's Republic of China.
  3. 3Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, 430010, People's Republic of China.
  4. 4Department of Gastrointestinal Surgery, The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510700, People's Republic of China.

Abstract

Objectives

This pilot study examined whether peripheral GRM2/GRM3 mRNA expression differed between chronic insomnia disorder (ID) and healthy controls (HCs) and correlated with emotional and polysomnographic (PSG) features.Methods

After PSG screening, 43 patients with chronic ID meeting DSM-5-TR criteria and 34 HCs with comparable age and sex distributions were included. Mood, sleep, and PSG parameters were assessed, and peripheral GRM2/GRM3 mRNA was quantified by RT-qPCR. Statistical analyses comprised group comparisons, age- and sex-adjusted regression, partial correlations with false discovery rate (FDR) correction, Bayesian analyses, sensitivity analyses, and exploratory receiver operating characteristic (ROC) analyses.Results

Compared with HCs, ID patients showed greater depressive and anxiety symptoms, poorer subjective sleep quality, and altered sleep architecture. Peripheral GRM2 and GRM3 mRNA expression was lower in ID patients, with both differences remaining significant after adjustment for age and sex (P=0.001; P=0.029). The apparent area under the curves (AUCs) were 0.744, 0.666, and 0.769 for GRM2, GRM3, and the combined model, respectively; corresponding cross-validated mean AUCs were 0.745, 0.645, and 0.732. Both GRM2 and GRM3 showed associations with emotional and sleep measures; the GRM3-PHQ-9 association remained significant after FDR correction (r=-0.373, P adj=0.020), while the GRM2-REM association showed Bayesian support (BF=4.473). These associations were attenuated after further adjustment for diagnostic group.Conclusions

Lower peripheral GRM2 and GRM3 expression was associated with chronic ID, with exploratory associations with selected emotional and sleep measures. These findings identify peripheral GRM2/GRM3 as candidate molecular correlates of ID. Independent external validation is required before clinical diagnostic application.

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BibTeX
@article{zhang2026peripheral,
  title = {{Peripheral GRM2 and GRM3 mRNA Alterations and Clinical Correlates in Insomnia Disorder: A Case-Control Pilot Study.}},
  author = {Liqing Zhang and Fangyi Deng and Jiaheng Lin and Jiwu Liao and Jiyang Pan},
  journal = {Neuropsychiatric disease and treatment},
  year = {2026},
  month = oct,
  doi = {10.2147/ndt.s642828},
  url = {https://europepmc.org/article/MED/42903742},
  note = {CC BY-NC},
}
RIS
TY  - JOUR
TI  - Peripheral GRM2 and GRM3 mRNA Alterations and Clinical Correlates in Insomnia Disorder: A Case-Control Pilot Study.
AU  - Liqing Zhang
AU  - Fangyi Deng
AU  - Jiaheng Lin
AU  - Jiwu Liao
AU  - Jiyang Pan
PY  - 2026
DA  - 2026/10/16
JO  - Neuropsychiatric disease and treatment
DO  - 10.2147/ndt.s642828
UR  - https://europepmc.org/article/MED/42903742
AB  - Objectives  This pilot study examined whether peripheral GRM2/GRM3 mRNA expression differed between chronic insomnia disorder (ID) and healthy controls (HCs) and correlated with emotional and polysomnographic (PSG) features.Methods  After PSG screening, 43 patients with chronic ID meeting DSM-5-TR criteria and 34 HCs with comparable age and sex distributions were included. Mood, sleep, and PSG parameters were assessed, and peripheral GRM2/GRM3 mRNA was quantified by RT-qPCR. Statistical analyses comprised group comparisons, age- and sex-adjusted regression, partial correlations with false discovery rate (FDR) correction, Bayesian analyses, sensitivity analyses, and exploratory receiver operating characteristic (ROC) analyses.Results  Compared with HCs, ID patients showed greater depressive and anxiety symptoms, poorer subjective sleep quality, and altered sleep architecture. Peripheral GRM2 and GRM3 mRNA expression was lower in ID patients, with both differences remaining significant after adjustment for age and sex (P=0.001; P=0.029). The apparent area under the curves (AUCs) were 0.744, 0.666, and 0.769 for GRM2, GRM3, and the combined model, respectively; corresponding cross-validated mean AUCs were 0.745, 0.645, and 0.732. Both GRM2 and GRM3 showed associations with emotional and sleep measures; the GRM3-PHQ-9 association remained significant after FDR correction (r=-0.373, P adj=0.020), while the GRM2-REM association showed Bayesian support (BF=4.473). These associations were attenuated after further adjustment for diagnostic group.Conclusions  Lower peripheral GRM2 and GRM3 expression was associated with chronic ID, with exploratory associations with selected emotional and sleep measures. These findings identify peripheral GRM2/GRM3 as candidate molecular correlates of ID. Independent external validation is required before clinical diagnostic application.
SN  - 1176-6328
SN  - 1178-2021
ER  -