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Abstract <p>Oxidative stress has been implicated in the pathophysiology of schizophrenia; however, the role of key antioxidant regulators such as sestrin-2 (SESN2) and nuclear factor erythroid 2-related factor 2 (NRF2) remains unexplored. Furthermore, whether these alterations are present in unaffected first-degree relatives, suggesting a potential genetic vulnerability marker, has not been investigated. This study aimed to compare serum SESN2 and NRF2 levels among patients with schizophrenia, their healthy siblings, and healthy controls, hypothesizing that both patients and their siblings would exhibit lower levels compared to controls<b>.</b> The study population consisted of 25 patients diagnosed with schizophrenia according to DSM-5 criteria, 25&#xa0;healthy siblings of these patients and 25 healthy controls. Scale for the Assessment of Negative Symptoms (SANS), Scale for the Assessment of Positive Symptoms (SAPS), Apathy Assessment Scale (AAS) and Short Form-36 (SF-36) Health Survey forms were administered to patients diagnosed with schizophrenia. Serum SESN2 and NRF2 levels of the participants were measured using ELISA method. When schizophrenia patients, their healthy siblings and control group were compared in terms of SESN2 and NRF2 levels, a statistically significant difference was found among groups (<i>p</i> &lt; 0.001). SESN2 and NRF2 levels were significantly lower in schizophrenia patients compared to their healthy siblings and control group (<i>p</i> &lt; 0.05). SESN2 and NRF2 levels were significantly lower in healthy siblings compared to the control group (<i>p</i> &lt; 0.001 and <i>p</i>&#xa0;= 0.009, respectively). To our knowledge, this is the first study to demonstrate reduced serum SESN2 and NRF2 levels in both schizophrenia patients and their unaffected siblings compared with healthy controls.</p>

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Investigation of Sestrin-2 and NRF2 Levels in Schizophrenia Patients, Their Healthy Siblings and Healthy Controls

  • 期刊论文

  • 发表日期：

    2026年7月19日

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  • Bahadır Demir,
  • Muhammet Sancaktar,
  • Emine Nur Sargın,
  • Gülçin Elboğa,
  • Feridun Bülbül,
  • Kenan Ercan,
  • Seyithan Taysı,
  • Abdurrahman Altındağ

摘要

Abstract

Oxidative stress has been implicated in the pathophysiology of schizophrenia; however, the role of key antioxidant regulators such as sestrin-2 (SESN2) and nuclear factor erythroid 2-related factor 2 (NRF2) remains unexplored. Furthermore, whether these alterations are present in unaffected first-degree relatives, suggesting a potential genetic vulnerability marker, has not been investigated. This study aimed to compare serum SESN2 and NRF2 levels among patients with schizophrenia, their healthy siblings, and healthy controls, hypothesizing that both patients and their siblings would exhibit lower levels compared to controls. The study population consisted of 25 patients diagnosed with schizophrenia according to DSM-5 criteria, 25 healthy siblings of these patients and 25 healthy controls. Scale for the Assessment of Negative Symptoms (SANS), Scale for the Assessment of Positive Symptoms (SAPS), Apathy Assessment Scale (AAS) and Short Form-36 (SF-36) Health Survey forms were administered to patients diagnosed with schizophrenia. Serum SESN2 and NRF2 levels of the participants were measured using ELISA method. When schizophrenia patients, their healthy siblings and control group were compared in terms of SESN2 and NRF2 levels, a statistically significant difference was found among groups (p < 0.001). SESN2 and NRF2 levels were significantly lower in schizophrenia patients compared to their healthy siblings and control group (p < 0.05). SESN2 and NRF2 levels were significantly lower in healthy siblings compared to the control group (p < 0.001 and p = 0.009, respectively). To our knowledge, this is the first study to demonstrate reduced serum SESN2 and NRF2 levels in both schizophrenia patients and their unaffected siblings compared with healthy controls.