IL-17 and TNF-β: Predictive biomarkers for transition to psychosis in ultra-high risk individuals

Lijun Ouyang; David Li; Zongchang Li; Xiaoqian Ma; Liu Yuan; Lejia Fan; Zihao Yang; Zhenmei Zhang; Chunwang Li; Ying He; Xiaogang Chen

doi:10.3389/fpsyt.2022.1072380

IL-17 and TNF-β: Predictive biomarkers for transition to psychosis in ultra-high risk individuals

Front Psychiatry. 2022 Dec 16:13:1072380. doi: 10.3389/fpsyt.2022.1072380. eCollection 2022.

Authors

Lijun Ouyang^{1

2}, David Li^{1

2}, Zongchang Li^{1

2}, Xiaoqian Ma^{1

2}, Liu Yuan^{1

2}, Lejia Fan^{1

2}, Zihao Yang^{1

2}, Zhenmei Zhang^{1

2}, Chunwang Li³, Ying He^{1

2}, Xiaogang Chen^{1

2}

Affiliations

¹ Department of Psychiatry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, China.
² Hunan Key Laboratory of Psychiatry and Mental Health, Mental Health Institute of Central South University, China National Technology Institute on Mental Disorders, Hunan Technology Institute of Psychiatry, Changsha, Hunan, China.
³ Department of Radiology, Hunan Children's Hospital, Changsha, China.

Abstract

Background: Dysregulation of immunity, such as levels of inflammatory factors, has been regarded as a sign of schizophrenia. Changes in cytokine levels are not only described in the early onset of disease, but also observed in ultra-high risk (UHR) individuals. This study aimed to investigate the potential of cytokines as biomarkers for psychotic disorders and in individuals at UHR of developing a psychotic disorder in the future.

Methods: The Luminex liquid chip technology was used to detect the concentrations of Interferon-gamma (INF-γ), Interleukin (IL)-2, Interleukin (IL)-4, Interleukin (IL)-6, Interleukin (IL)-17, Interleukin-1beta (IL-1β), and Tumor Necrosis Factor-beta (TNF-β) in the plasma of all subjects. Meanwhile, the plasma level of Tumor Necrosis Factor-Alpha (TNF-α) was measured with the enzyme-linked immunosorbent assay (ELISA) kits. Then, the levels of these cytokines were compared among patients with Drug-naïve first-episode schizophrenia (FES; n = 40), UHR population (UHR; n = 49), and healthy controls (HCs; n = 30). Baseline cytokine levels were compared among UHR individuals who later transitioned (UHR-T; n = 14), those who did not transition (UHR-NT; n = 35), and HCs (n = 30).

Results: Our analysis results showed that IL-1β levels were significantly higher in UHR group than HC group (p = 0.015). Meanwhile, TNF-α concentration was significantly increased in FES group compared with HC group (p = 0.027). IL-17 (p = 0.04) and TNF-β (p = 0.008) levels were significantly higher in UHR-T group compared with UHR-NT group.

Conclusion: In conclusion, our findings suggest that the immuno-inflammatory activation level is increased in the early stage of psychosis before psychotic conversion and the Drug-naïve FES. IL-1β and TNF-α are the representatives of the specific biomarkers for UHR and FES, respectively. IL-17 and TNF-β may be the potential selective predictive biomarkers for future transition in UHR individuals.

Keywords: Drug-naïve first-episode; cytokines; inflammation; schizophrenia; ultra-high risk individual.