Role of N-methyl-d-aspartate receptors in anxiety disorder with thyroid lesions.

Patients with anxiety disorder (AD) often have structural and functional abnormalities of the thyroid gland, but their specific causes remain unclear. N-methyl- d-aspartate receptors (NMDARs) play an important role in many psychosomatic diseases and tumorigenesis, but there are few reports on the role of NMDARs in AD with thyroid lesions, especially thyroid nodules (TNs). A cross-sectional study was conducted on patients admitted to the hospital with AD (n = 71) as the main diagnosis from April to October 2021. Meanwhile, patients with TNs with no AD (NAD-TN group, n = 20) and healthy subjects (HS group, n = 37) with matched age, sex, and education were randomly collected as controls. Patients with AD were sub-grouped into the AD with TNs (AD-TN group, n = 41) and the AD with no TNs (AD-NTN group, n = 30). The thyroid ultrasound reports, Hamilton Anxiety Scale (HAMA) scores, and the expression of NMDARs and their subunits (NR1, NR2A, and NR2B) and hypothalamic-pituitary-thyroid (HPT) axis-related hormones were analyzed in all subjects. Some patients with TNs underwent surgery and postoperative pathological examination. Patients with AD showed a lower level of free triiodothyronine (FT3) and higher levels of thyrotropin-releasing hormone (TRH) and NMDARs and their subunits compared to the healthy controls. The expression of the NR2A subunit was higher in the AD-TN group than that in other three groups (AD-NTN, NAD-TN, and HS groups, F = 13.650, p < 0.001). Regression analysis showed that the level of NMDARs was positively correlated with the HAMA scores (B = 1.622, p = 0.029) and the maximum diameter of TNs (B = 3.836, p = 0.005). Immunohistochemical results showed that the NR2A subunit was widely expressed in multinodular goiter (MNG) and papillary thyroid carcinoma (PTC) tissues, while the expression of the NR2B subunit was lower in PTC adjacent and MNG tissues and almost absent in PTC tissues. In a sample of mostly women hospitalized with generalized anxiety disorder (GAD) or panic disorder, abnormal expression of NMDARs is closely related to AD with thyroid lesions, NMDAR subunits may have various activities and exert diverse effects in TNs, and the NR2A subunit may be an important regulator in AD with TNs.

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