Human-induced pluripotent stem cells in psychiatric disorders: An inflammatory perspective

Adv Immunol. 2026;171:109-146. doi: 10.1016/bs.ai.2026.04.004. Epub 2026 May 29.

ABSTRACT

Psychiatric disorders have long been associated with inflammation- either as prolonged mental illnesses leading to immune dysregulations or as psychiatric conditions arising from systemic inflammation. Physiologically, inflammation is one of the responses to bodily stress, however, the degree of inflammation depends on the type and duration of the stressor. Here, we focus on understanding both- inflammation-induced brain cellular response alterations and neuroinflammation caused by an underlying psychiatric condition. Apart from post-mortem brains, the closest approach by which one can recreate both these phenomena are by using patient-derived induced pluripotent stem cells (IPSCs), as the brain tissue is inaccessible. Therefore, we focus on studies using IPSC-derived brain cells from patients to model inflammation across psychiatric conditions. Unlike any other available model system, IPSCs hold a major advantage of carrying patients’ genetic background that is crucial to understand disorders as complex and enigmatic as psychiatric disorders. When knowledge on patients’ genetic risks and environmental exposures are integrated into patient iPSC-derived brain cellular models, it holds enormous potential to delineate psychiatry related pathophysiology from other comorbidities. Therefore, understanding the cellular responses to inflammation and treatment helps us refine the existing therapeutic strategies and initiate early interventions to better manage psychiatric disorders.

PMID:42629122 | DOI:10.1016/bs.ai.2026.04.004