Influence of the inflammasome complex on psychiatric disorders: clinical and preclinical studies

ABSTRACT

Introduction

The innate immune complex, an inflammasome complex, has a role in the etiology of psychiatric disorders. Preclinical studies have demonstrated that the inflammasome activation leads to psychiatric disorders and clinical studies have proved that specific psychiatric illnesses are associated with aberrant levels of inflammatory cytokines and inflammasome. The inflammasome complex could be a major factor in the progression and pathology of psychiatric disorders.

Area covered

We discuss the pathogenesis of psychiatric disorders with respect to the activation of the inflammasome complex. Inflammasome-associated inflammatory cytokines are observed in patients and animal models of psychiatric disorders. The article also reflects on inflammasome regulatory options for the prevention and treatment of psychiatric disorders. Relevant literature available on PubMed from 1992 to 2021 has been included in this review.

Expert opinion

Modulating the inflammasome complex is a potential therapeutic strategy to treat symptom severity for patients with psychiatric disorders, particularly those with inflammasome-associated disorders. However, the nature of the psychiatric disorders should be considered when targeting inflammasome.

KEYWORDS:

• Anxiety disorder
• bipolar disorder
• inflammasome
• major depressive disorder
• psychiatric disorder

Author’s contribution

S.Y.C designed this study and wrote the manuscript. S.Y.C. and S.K. made figures/tables. S.K. provided comments. S.Y.C. revised the manuscript and finalized the manuscript. All authors read and approved the final version of this manuscript.

Article highlights

• A growing number of studies have confirmed that abnormal inflammatory responses are involved in psychiatric disorders.

• The inflammasome complex belongs to innate immunity and quickly responds to various stimuli.

• External or internal stressors result in the activation of the inflammasome complex and high levels of inflammatory cytokines, which activate the hypothalamic–pituitary–adrenal (HPA) axis and trigger the secretion of glucocorticoid hormones.

• Inflammasome complex components or inflammasome-driven inflammatory cytokines are considered key factors in the pathogenesis or progression of psychiatric disorders.

• Preclinical studies have shown that NLRP3 inhibitors, caspase-1 inhibitors, and antioxidants improve the symptoms of psychiatric disorders.

• In preclinical studies, genetic or chemical modulation of inflammasome activation has been shown beneficial effects in the prevention and treatment of psychiatric disorders.

• Patients with psychiatric disorders might benefic from therapies involving the targeting of the inflammasome.

Disclosure statement

The author has no relevant affiliation or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. The authors declare no conflicts of interest. The funders had no role in the design of this study, the writing of the manuscript, or the decision to publish this paper.

Additional information

Funding

Funding This article was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2020R1C1C1010613) to So Yeong Cheon.