Reduced Serum Levels of Soluble Interleukin-15 Receptor α in Schizophrenia and Its Relationship to the Excited Phenotype.

Min Liu,Abba J Kastin,Zhen Mao,Weihong Pan,Qijing Bo,Haixia Wang,Jian Yang,Yi He,Zuoli Sun,Chuanyue Wang

doi:10.3389/fpsyt.2022.842003

Abstract

Our previous studies documented that interleukin-15 receptor α (IL-15Rα) knockout (KO) mice exhibited hyperactivity, memory impairment, and desperate behavior, which are core features of schizophrenia and depression. Due to the overlapping symptomology and pathogenesis observed for schizophrenia and depression, the present study attempted to determine whether IL-15Rα was associated with the risk of schizophrenia or depression. One hundred fifty-six participants, including 63 schizophrenia patients, 29 depressive patients, and 64 age-matched healthy controls, were enrolled in the study. We investigated the circulating levels of soluble IL-15Rα and analyzed potential links between the IL-15Rα levels and clinical symptoms present in schizophrenia or depressive patients. We observed reduced serum IL-15Rα levels in schizophrenia patients, but not depressive patients compared with controls. Moreover, a significant negative association was observed between the circulating IL-15Rα levels and excited phenotypes in the schizophrenia patients. The IL-15Rα KO mice displayed pronounced pre-pulse inhibition impairment, which was a typical symptom of schizophrenia. Interestingly, the IL-15Rα KO mice exhibited a remarkable elevation in the startle amplitude in the startle reflex test compared to wild type mice. These results demonstrated that serum levels of soluble IL-15Rα were reduced in schizophrenia and highlighted the relationship of IL-15Rα and the excited phenotype in schizophrenia patients and mice.

Highlights

Psychiatric disorders, such as schizophrenia and major depressive disorder (MDD), result from complex interactions between genetic and environmental factors that lead to developmental or neurological impairment [1, 2]
The present study investigated potential connections between interleukin-15 receptor α (IL-15Rα) levels in serum and the risk of schizophrenia and depression
(1) Patients with schizophrenia but not depression showed significant reductions in serum IL-15Rα levels compared to healthy controls

Summary

Introduction

Psychiatric disorders, such as schizophrenia and major depressive disorder (MDD), result from complex interactions between genetic and environmental factors that lead to developmental or neurological impairment [1, 2]. Considerable evidence indicates that disruption of the immune system due to inflammation has a critical role in psychiatric disorders, including schizophrenia and depression [3, 4, 7]. Recent data indicate the presence of typical inflammation responses in schizophrenia and depression [3, 8– 10]. Epidemiological studies have revealed that the presence of an autoimmune disease is a high-risk factor for psychiatric disorders [11, 12]. A series of genome-wide association studies (GWAS) of schizophrenia confirmed that the immune system is involved in the pathogenesis of schizophrenia and depression, including the HLA gene (a complement gene) and the interleukin gene family [13–15]. Animals with overactive inflammatory cytokines displayed schizophrenia- or depressivelike behaviors, and the cytokines induced neuronal loss and synaptic impairment [20, 21], which are common characteristics observed in schizophrenia and depression

Methods

Results

Conclusion