Increased circulating IL-18 levels in severe mental disorders indicate systemic inflammasome activation

Area of Science:

• Neuroscience
• Immunology
• Psychiatry

Background:

• Schizophrenia (SCZ) and bipolar disorder (BD) are severe mental illnesses (SMI) linked to psychosis.
• Dysregulated innate immune responses are implicated in SMI pathophysiology.
• Cholesterol dyslipidemia has been associated with systemic inflammasome activation in SMI.

Purpose of the Study:

• To investigate if SCZ and BD patients exhibit elevated IL-18 system components compared to healthy individuals.
• To explore associations between inflammasome markers, lipid profiles, and coronary artery disease risk factors in SMI.

Main Methods:

• A large cohort study including 737 SCZ patients, 895 BD patients, and 1070 healthy controls (CTRL).
• Quantification of circulating IL-18 system components (IL-18, IL-18BPA, IL-18R1).
• Assessment of inflammasome-related gene expression (NLRP3, NLRC4) and lipid markers.

Main Results:

• Patients with SCZ and BD showed significantly higher levels of IL-18 system components and inflammasome gene expression compared to CTRL.
• A distinct cholesterol dyslipidemia pattern was observed in patients with psychotic disorders.
• Correlations were found between blood cholesterol levels and inflammasome system element expression in SMI.

Conclusions:

• Inflammasome activation and dysregulation likely play a role in the pathophysiology of SMI.
• Findings enhance understanding of inflammatory mechanisms in SCZ and BD.
• These insights may identify novel therapeutic targets for severe mental illnesses.