Current insight into the role of natural killer (NK) cells in schizophrenia: A Narrative Literature Review

Abstract

Background: schizophrenia is chronic psychiatric disorder characterized by disturbances in thought, perception and behaviour and is increasingly linked to immune dysregulation involving both innate and adaptive systems. Natural killer cells are innate lymphocytes characterised by their cytotoxic and immune functions. This narrative review synthesises human studies evaluating NK cell number, phenotype, function and transcriptomic signatures in schizophrenia and related psychotic disorders.

Methods: We conducted a structured literature search across PubMed, Google Scholar, One Nation One subscription, and freely available articles up to 30 November 2025. Studies of individuals diagnosed with schizophrenia spectrum disorders that reported NK-cell counts, receptor/phenotype data, cytotoxicity assays, or related transcriptomic markers were included. Selection and data extraction were performed independently by authors (MK, DR), with ZOTERO used to deduplicate references.

Results: Evidence is heterogeneous but converging. Several studies report reduced peripheral NK-cell proportions and altered maturation/receptor profiles (e.g., shifts in CD56 subsets and NKG2C expression), while other reports indicate stage-dependent or compensatory activity. Genetic and transcriptomic analyses implicate broader immune and inflammatory pathways that may affect NK biology. Interactions with dopaminergic signalling in methodology, clinical stage, medication exposure and sample handling substantially limit direct comparisons.

Conclusion: NK cells appear to be a relevant but incompletely characterized component of immune dysregulation in schizophrenia. Standardised, longitudinal and mechanical studies are required to determine whether NK measures can serve as biomarkers or therapeutic targets.