Review finds different immune-receptor patterns in schizophrenia and mood disorders

Researchers combined results from 26 previous studies that measured messenger RNA, or mRNA, for toll-like receptors in peripheral blood. mRNA is a molecule cells use to make proteins. Measuring it can offer a snapshot of how active particular genes are.

Toll-like receptors, often shortened to TLRs, are part of innate immunity. This is the immune system's rapid first response to possible threats. The review examined TLR1 through TLR10 in people with schizophrenia spectrum disorders or mood disorders, compared with healthy control participants.

The included studies involved 678 people with schizophrenia spectrum disorders, 523 people with mood disorders and 1,182 healthy controls. Mood disorders in the coverage included depression and bipolar disorder. The researchers searched five scientific databases for eligible studies published through September 2025.

The team used a random-effects meta-analysis, a method that pools findings while allowing for differences between the individual studies. They also conducted sensitivity analyses and meta-regressions. The abstract does not provide further details about the results of those checks.

For schizophrenia spectrum disorders, expression of TLR4, TLR8 and TLR10 was significantly higher than in healthy controls. The reported effect sizes, measured with a statistic called Hedges' g, ranged from 0.26 to 0.31. These are small average differences.

For mood disorders, TLR2, TLR5 and TLR6 had significantly higher expression than in healthy controls. Their effect sizes ranged from 0.23 to 0.32, also small differences. The researchers adjusted for the fact that they tested multiple receptors, and the reported findings remained statistically significant after that adjustment.

The authors describe the pattern in schizophrenia spectrum disorders as broader and potentially responsive to a wider range of microbial signals. The mood-disorder pattern appeared more restricted and predominantly antibacterial. These descriptions are interpretations of the receptors involved, not proof that infections or any particular immune trigger causes either group of conditions.

Importantly, this was a review of blood-based measurements, not a study of the brain. A higher mRNA level in peripheral blood does not by itself show what is happening in brain tissue, whether the immune changes came before illness, or whether they are affected by symptoms, medications, lifestyle, or other health factors.

The study also cannot establish cause and effect. People in these diagnostic groups had different average receptor-expression patterns in the studies reviewed, but that does not mean the receptor changes caused schizophrenia, depression, or bipolar disorder. Nor does it mean an individual person's TLR results could identify a diagnosis.

The findings are best viewed as a research lead. They may help scientists study whether biological patterns differ across psychiatric diagnoses and whether those patterns are linked to illness pathways. The authors say longitudinal studies, which follow people over time, along with experimental and multi-omics research, are needed for clearer answers. Multi-omics studies examine several kinds of biological data together, such as genes, proteins and other molecules.

For now, the review adds evidence that immune-related biology may vary across these diagnostic groups, while leaving major questions about timing, causes and practical clinical use unanswered.