Immunophenotypes in psychosis: is it a premature inflamm-aging disorder?

Abstract

Immunopsychiatric field has rapidly accumulated evidence demonstrating the involvement of both innate and adaptive immune components in psychotic disorders such as schizophrenia. Nevertheless, researchers are facing dilemmas of discrepant findings of immunophenotypes both outside and inside the brains of psychotic patients, as discovered by recent meta-analyses. These discrepancies make interpretations and interrogations on their roles in psychosis remain vague and even controversial, regarding whether certain immune cells are more activated or less so, and whether they are causal or consequential, or beneficial or harmful for psychosis. Addressing these issues for psychosis is not at all trivial, as immune cells either outside or inside the brain are an enormously heterogeneous and plastic cell population, falling into a vast range of lineages and subgroups, and functioning differently and malleably in context-dependent manners. This review aims to overview the currently known immunophenotypes of patients with psychosis, and provocatively suggest the premature immune “burnout” or inflamm-aging initiated since organ development as a potential primary mechanism behind these immunophenotypes and the pathogenesis of psychotic disorders.

Longitudinal course of inflammatory-cognitive subgroups across first treatment severe mental illness and healthy controls

“…It is increasingly clear that only a subset of individuals with SMI show signs of increased systemic inflammation (Bishop et al, 2022; Chen et al, 2024; Miller and Goldsmith, 2019), partly explaining mixed or weak associations between inflammatory markers and cognition in case-control studies (Bora, 2019; Miller and Goldsmith, 2019; Morrens et al, 2022). This is also in line with genetic findings of mixed effect directions, which includes higher load of increasing and decreasing genetic variants for CRP in SMI (Hindley et al, 2023).…”