Lower Serum Annexin A1 and Neurogranin Levels in Chronic Schizophrenia Patients

A single-center case–control study has identified significantly lower levels of two specific serum biomarkers, Annexin A1 (ANXA1) and neurogranin (Ng), in patients diagnosed with chronic schizophrenia compared to healthy controls. These findings suggest potential peripheral correlates for underlying synaptic dysfunction and immune mechanisms implicated in the pathophysiology of the disorder, although the study emphasizes that these results are exploratory and require further replication.

The research enrolled 70 participants: 35 individuals meeting the DSM-5 criteria for schizophrenia, specifically diagnosed using the SCID-5, and 35 sex-comparable healthy controls. The primary analytical goal was to measure fasting serum concentrations of ANXA1 and Ng using a sandwich enzyme-linked immunosorbent assay (ELISA). These proteins are of interest because ANXA1 functions as a glucocorticoid-induced pro-resolving protein, while Ng is a post-synaptic, calmodulin-binding protein frequently studied as a peripheral indicator of synaptic biology.

The results demonstrated a statistically significant reduction in both biomarkers within the patient group. For ANXA1, the median level in the schizophrenia patients was 6.21 ng/mL (interquartile range [IQR] 5.12–8.34), which was substantially lower than the median of 13.06 ng/mL (IQR 8.82–23.66) observed in the healthy control group. This difference was highly significant (U = 309, p = 3.6 × 10⁻⁴; rank-biserial r = − 0.50). Similarly, serum neurogranin levels were markedly lower in the patient cohort, with a median of 174.2 pg/mL (149.1–281.0) compared to 380.0 pg/mL (237.1–547.1) in controls (U = 302, p = 2.7 × 10⁻⁴; r = − 0.51).

Crucially, these group differences remained statistically significant even after applying rigorous statistical corrections, including Bonferroni and false-discovery-rate corrections for multiple testing. Furthermore, when adjusting for potential confounding variables such as age, sex, and body-mass index using analysis of covariance (ANCOVA), the reduced levels persisted. The adjusted difference for ANXA1 was found to be -6.71 ng/mL (p = 0.011), and for Ng, it was -182.3 pg/mL (p = 0.0008).

The study also investigated the relationship between these two biomarkers within the participant groups. A strong positive correlation was observed between ANXA1 and Ng levels in the patient group (r = 0.900) and also in the control group (r = 0.844). The analysis confirmed that there was no significant difference in the correlation between the two groups (Fisher r-to-z, p = 0.339). Moreover, neither ANXA1 nor Ng showed a significant association with the clinical symptom severity measures, specifically the PANSS (Positive and Negative Syndrome Scale) or CGI-S (Clinical Global Impression of Severity).

The researchers also examined whether the levels of these biomarkers were influenced by various treatment factors commonly associated with schizophrenia management. Specifically, they assessed associations with chlorpromazine-equivalent dose, clozapine usage, antipsychotic polypharmacy, the use of long-acting injectables, or lifetime electroconvulsive therapy. The results indicated that neither Annexin A1 nor neurogranin levels were significantly associated with any of these documented treatment variables.

Within the cohort, sex-stratified differences in biomarker levels were noted to reach significance only in women, although the overall group × sex interaction was not statistically significant. This suggests potential sex-specific biological mechanisms related to these proteins, warranting further investigation into gender-based differences in the progression or presentation of schizophrenia.

Despite the compelling nature of the observed reductions, the authors were clear about the limitations of this single-center, case–control design. They explicitly stated that because no inflammatory, central nervous system, or longitudinal measures were obtained, these exploratory findings cannot definitively demonstrate impaired resolution of inflammation, altered central synaptic integrity, or reflect a true trait status of the disorder. The study serves primarily to identify two candidate peripheral markers that necessitate subsequent replication in larger, more comprehensive studies.

Subject of Research: Investigation into the lower levels of Annexin A1 and neurogranin in the serum of patients diagnosed with chronic schizophrenia.

Article Title: Lower serum annexin A1 and neurogranin levels in chronic schizophrenia: a case–control study

Article References: Sancaktar, M., Demir, B., Yağdıran, E. N., Elboğa, G., Bülbül, F., Ercan, K., Taysı, S., & Altındağ, A. (2026). Lower serum annexin A1 and neurogranin levels in chronic schizophrenia: a case–control study. BMC Psychiatry. https://doi.org/10.1186/s12888-026-08822-3

Image Credits: AI Generated

DOI: 10.1186/s12888-026-08822-3

Keywords: Schizophrenia, Neurogranin, Annexin A1, Synaptic Dysfunction, Case-Control Study, Psychiatry, Biomarkers, Lower, serum, annexin, levels, chronic