To our knowledge this is the first study investigation of Epo and EpoR in patients with GAD. We found that the levels of Epo in patients with GAD were lower than the control patients. However, EpoR levels were increased in these patients. This situation may be due to increased of neuroinflammation in patients with GAD. Camacho recommended that anxious-depression should be considered as a chronic inflammatory phenomenon but the only longitudinal study found the association between GAD and increased C-reactive protein (CRP) level to be attributable to body mass index and medication use [12, 13]. A large cohort study examined the association between anxiety disorders (including GAD, social phobia, PD, and agoraphobia) and inflammation, and the some authors reported elevated CRP levels in male patients with current anxiety disorders and immune dysregulation in patients with a late-onset anxiety disorder . Furthermore, an integrated specificity model emphasizes specific patterns of biological responses to specific psychological states and an anxiety-specific effect on inflammatory activity in clinically anxious individuals has been reported [15–17]. Recent studies have characterized Epo as a potent anti-inflammatory cytokine in chronic inflammatory disorders and infectious diseases . Also, recently, multiple lines of evidence have shown that both endogenous and exogenous Epo has protective roles in CNS injury processes, such as ischemia-reperfusion injury. Although the presence of functional EpoRs in neurons has been challenged, Epo selectively reduced inflammatory and oxidative stress processes associated with brain ischemia, and prevented neuronal apoptosis [19–24].
In our study, decreased levels of Epo/EpoR ratio may due to low Epo levels. Until now, Epo/EpoR ratio has not been reported in patients with GAD. So, we did not compared to our results. This study suggests that efforts aiming to increase either Epo expression or the activation of EpoR in the GAD may be a promising target for GAD treatment, especially in stopping the progression, and potentially reversing the well known behavioral morbidities.
High correlation values constitute an important part of our findings. The correlation coefficient is shown with the ‘r’ symbol. A “r value” ≤0.35 represents low or weak correlation, between 0.36 and 0.67 shows moderate correlation, 0.68 to 0.90 shows high correlation, and 0.90 to 1.0 shows very high correlation . We found that a significant negative correlation between HAM-A scores and Epo levels. However, we found that a positive correlation between HAM-A scores and EpoR levels. There are no studies between Epo and HAM-A scores, or between EpoR and HAM-A scores in patients with GAD. So, we did not compared to our results. We believe that a high correlation coefficient forms a basis for the detection of biomarkers.
Identifying diagnostic biomarkers for psychiatric disorders is a rising topic of interest. In some previous studies peripheral markers were proposed for diverse psychiatric disorders. For GAD, Bulut et al. found paraoxonase activity and the AUC value was 0.980 . Furthermore, Güneş et al. showed prolidase was a good biomarker for schizophrenia (AUC:1.000) . Currently, a growing body of evidence exists regarding diagnostic value of several peripheral parameters in psychiatric disorders. From this scope, our study shows possible implication for hormon receptor (Epo-EpoR) level as an important research area for detection of peripheral biomarkers.
The limitations of the present study were inclusion of small number of patients and its cross-sectional design. Nevertheless, to our knowledge, there is no study in the literature assessing the serum Epo and EpoR levels in GAD patients; accordingly, this study has the feature of being the first study on this issue. Moreover, all patients were drug-naive. The outcome of the present study is an important in terms of providing data for a treatment approach through target receptors in GAD.