Relationship between symptom severity, glutamate levels, and N-methyl-D-aspartate receptor target microRNA expression in patients with panic disorder

Abstract

Background Glutamate, an excitatory neurotransmitter in the central nervous system, plays a role in neurodevelopment, learning, and memory. It is thought to interact with the GABAergic system in the development of panic symptoms; however, the relationship between blood glutamate levels and panic disorder severity remains unclear. While research on miRNAs is increasing, studies on their role in panic disorder are limited. This study aimed to evaluate blood glutamate levels and the expression of miR-138-2-3p, which affects glutamate receptors, in panic disorder. Methods The study included 46 panic disorder patients and 46 healthy controls. All participants completed sociodemographic, Panic Disorder Severity Scale (PDSS), Anxiety Sensitivity Index-3 (ASI-3), and Somatosensory Exaggeration Scale (SSAS) forms. Peripheral venous blood was collected for genetic and biochemical analysis. MicroRNA expression was assessed by real-time PCR, and glutamate levels were measured using ELISA. Results Patients with panic disorder exhibited significantly lower plasma glutamate levels compared with healthy controls, with median values (25-75% percentiles) of 96.7 nmol/ml (51.39-133.62) versus 209 nmol/ml (95.6-521.9, P < 0.001). Moreover, glutamate levels were negatively associated with symptom severity as measured by the PDSS, ASI-3, and SSAS. In parallel, miR-138-2-3p expression was significantly reduced in patients relative to controls, with median ratios (25-75% percentiles) of 0.27 (0.14-0.57) versus 0.48 (0.23-0.98, P = 0.034), corresponding to a 1.77-fold higher expression in controls. Conclusion Altered miR-138-2-3p expression and reduced peripheral glutamate levels may contribute to the pathophysiology and clinical severity of panic disorder.