Oxidative stress markers predict treatment outcomes in patients with generalized anxiety disorder treated with selective serotonin reuptake inhibitors

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Abstract

Introduction The etiology of generalized anxiety disorder (GAD) has not been fully understood, and oxidative stress may potentially contribute to its pathogenesis. However, there is no published evidence concerning the possible influence of oxidative stress on antidepressant treatment outcomes. This study investigated the ability of oxidative stress markers to predict treatment outcomes in GAD patients treated with selective serotonin reuptake inhibitors (SSRIs). Methods One hundred-one GAD patients and 100 healthy controls (HCs) were included in this study. The 101 GAD patients were selected for treatment with escitalopram (n=52) or sertraline (n=49) for eight weeks. Hamilton Anxiety Rating Scale (HAM-A) assessments were conducted before and after treatment. The serum levels of eight oxidative stress makers, malondialdehyde (MDA), lipid hydroperoxides (LPO), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), cortisol, high-density lipoprotein (HDL), and nitric oxide (NO) were measured using enzyme-linked immunosorbent assays (ELISA) before and after SSRI treatment in GAD patients and at the time of HCs enrollment. Results The serum levels of MDA, cortisol, and LPO were higher in GAD patients than in HCs (all p<.001 ), while SOD, GSH-Px, and CAT were lower than in HCs (all p<.001 ). The baseline MDA, LPO, NO, and cortisol levels were positively correlated with anxiety severity, while GSH-Px was negatively correlated. After eight weeks of SSRI treatment, the GSH-Px levels increased, and MDA and LPO decreased (all p<.05 ). Alterations in MDA levels co-varied with changes in anxiety measures (all p<.05 ). The ability of the receiver operating characteristic (ROC) area of the baseline MDA levels to predict the SSRI endpoint treatment response was 0.804 ( p<.05 ). Conclusion The pathogenesis of GAD might involve oxidative stress. Moreover, serum MDA levels might predict treatment response to SSRIs. However, more research is warranted to confirm these findings.
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Abstract

Introduction The etiology of generalized anxiety disorder (GAD) has not been fully understood, and oxidative stress may potentially contribute to its pathogenesis. However, there is no published evidence concerning the possible influence of oxidative stress on antidepressant treatment outcomes. This study investigated the ability of oxidative stress markers to predict treatment outcomes in GAD patients treated with selective serotonin reuptake inhibitors (SSRIs).

Methods

One hundred-one GAD patients and 100 healthy controls (HCs) were included in this study. The 101 GAD patients were selected for treatment with escitalopram (n=52) or sertraline (n=49) for eight weeks. Hamilton Anxiety Rating Scale (HAM-A) assessments were conducted before and after treatment. The serum levels of eight oxidative stress makers, malondialdehyde (MDA), lipid hydroperoxides (LPO), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), cortisol, high-density lipoprotein (HDL), and nitric oxide (NO) were measured using enzyme-linked immunosorbent assays (ELISA) before and after SSRI treatment in GAD patients and at the time of HCs enrollment.

Results

The serum levels of MDA, cortisol, and LPO were higher in GAD patients than in HCs (all p<.001), while SOD, GSH-Px, and CAT were lower than in HCs (all p<.001). The baseline MDA, LPO, NO, and cortisol levels were positively correlated with anxiety severity, while GSH-Px was negatively correlated. After eight weeks of SSRI treatment, the GSH-Px levels increased, and MDA and LPO decreased (all p<.05). Alterations in MDA levels co-varied with changes in anxiety measures (all p<.05). The ability of the receiver operating characteristic (ROC) area of the baseline MDA levels to predict the SSRI endpoint treatment response was 0.804 (p<.05).

Conclusion

The pathogenesis of GAD might involve oxidative stress. Moreover, serum MDA levels might predict treatment response to SSRIs. However, more research is warranted to confirm these findings. Competing Interest Statement The authors have declared no competing interest. Funding Statement the Health Science and Technology Plan of Zhejiang Province (2022KY367, Xinhua Shen), Huzhou City Science and Technology Plan Public Welfare Application Research Project Population Health (2022 GZ66, Xinhua Shen), and Huzhou Public Welfare Research Project Social Development Category (2021GY38, Lijun Cui) Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by the Ethics Committee of Huzhou Third Municipal Hospital (approval no. 2021-017). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes

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