2026 ECNP Congress

PS01-1236

Associations between GABA and glutamate levels with pain presence and depressive symptoms in obstructive sleep apnea

Agata Gabryelska — P. Kaczmarski, P. Białasiewicz, D. Strzelecki, J. Jaromirska, D. Jarecki, S. Turkiewicz · Medical University of Lodz, Department of Sleep Medicine and Metabolic Disorders, Lodz, Poland

2026 ECNP Congress

Introduction. Obstructive sleep apnea (OSA) is a common sleep disorder characterized by recurrent upper airway collapse during sleep. Patients with OSA frequently present with various comorbidities, including pain disorders and depression. Dysregulation of glutamate and gamma-aminobutyric acid (GABA) neurotransmission may contribute to these symptoms; however, their role in OSA remains insufficiently understood. This study aimed to evaluate serum levels of GABA and glutamate in OSA patients and their differences associated with the presence of pain and depressive symptoms.

Methods. The study included 80 participants who underwent polysomnography (PSG) and were classified based on the apnea–hypopnea index (AHI) into a control group (n=35; AHI<5) and OSA group (n=45; AHI≥30). Depressive and pain symptoms were assessed using the Montgomery–Åsberg Depression Rating Scale (MADRS) and the pain subscale of the Short Form 36 (SF-36) Health Survey, respectively. Morning blood samples were collected after PSG, and serum GABA and glutamate levels were measured using ELISA.

Results. No differences between OSA and control groups were observed in GABA levels (383.55 vs 391.29ng/ml; p=0.805), while the glutamate concentration was higher in OSA compared to the control group (2.10 vs. 1.84mM; p=0.021). In the univariate general linear model, the difference remained statistically significant (p=0.045) while controlling for covariates (BMI and age) and explained 3.8% of the glutamate concentration variance.

OSA and control groups were similar regarding the frequency of individuals reporting substantial pain presence (41.9 vs. 37.5%; p=0.739), SF pain score (51 vs. 51; p=1.000), MADRS score (9.5 vs. 12; p=0.605), and prevalence of at least mild depression (81.3 vs. 73.1%; p=0.458).

In the OSA group, individuals with substantial pain had higher GABA and glutamate levels (385.67 vs. 379.16ng/ml; p=0.056, and 2.03 vs. 1.86mM; p=0.005, respectively) and a higher MADRS score (16 vs. 8; p=0.007). None of these differences were present in the control group.

Furthermore, the SF pain score correlated with GABA and glutamate levels and MARDS score (R=-0.391, p=0.003 and R=-0.572, p<0.001, respectively) in OSA but not in the control group. Additionally, in the OSA group, the relationship between the MADRS score and glutamate (R=-0.501, p=0.003), but not GABA levels (R=0.258, p=0.147), was observed only in the OSA group. Interestingly, the SF pain score was associated with the arousal index (R=-0.417, p=0.043) only in the control group. Moreover, the correlation between SF pain score and the severity of daytime sleepiness (R=-0.565, p<0.001) was present only in the OSA group.

Conclusions. Patients with OSA exhibit elevated serum glutamate levels, independent of age and BMI, suggesting altered excitatory neurotransmission in this population. While overall pain and depressive symptoms did not differ between groups, significant associations between glutamate, GABA, pain, and depressive symptoms were observed exclusively in OSA patients. These findings indicate that neurochemical dysregulation may contribute to the interplay between pain and mood disturbances, specifically in OSA. The absence of such relationships in controls highlights a disease-specific mechanism. Overall, glutamatergic pathways may play a key role in symptom expression in OSA and represent a potential target for future research and therapeutic interventions.

References

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