Lower serum annexin A1 and neurogranin levels in chronic schizophrenia: a case–control study
- 1Department of Psychiatry, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey
- 2Department of Biochemistry, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey
Abstract
Background: Synaptic dysfunction and immune mechanisms are both implicated in schizophrenia. Annexin A1 (ANXA1) is a glucocorticoid-induced pro-resolving protein and neurogranin (Ng) is a post-synaptic, calmodulin-binding protein studied as a peripheral correlate of synaptic biology. Circulating ANXA1 has not previously been measured in schizophrenia, and serum Ng is sparsely characterised, so no directional hypothesis was pre-specified.
Methods: In a single-centre case–control study, 35 patients meeting DSM-5 criteria for schizophrenia (diagnosed with the SCID-5) and 35 sex-comparable healthy controls were enrolled. Fasting serum ANXA1 and Ng were measured in duplicate by sandwich enzyme-linked immunosorbent assay. Symptom severity was rated with the PANSS and CGI-S, and antipsychotic treatment was documented including chlorpromazine equivalents. The pre-specified primary analysis was the Mann–Whitney U test for each biomarker, with Bonferroni and false-discovery-rate correction; group differences were then adjusted for age, sex and body-mass index by analysis of covariance. All other analyses were exploratory.
Results: Both biomarkers were lower in patients: ANXA1 median 6.21 (IQR 5.12–8.34) vs. 13.06 (8.82–23.66) ng/mL (U = 309, p = 3.6 × 10⁻⁴; rank-biserial r = − 0.50) and Ng 174.2 (149.1–281.0) vs. 380.0 (237.1–547.1) pg/mL (U = 302, p = 2.7 × 10⁻⁴; r = − 0.51). Both remained significant after correction for multiple testing and in ANCOVA adjusted for age, sex and body-mass index (adjusted difference − 6.71 ng/mL, p = 0.011; −182.3 pg/mL, p = 0.0008). Neither biomarker was associated with chlorpromazine-equivalent dose, clozapine use, antipsychotic polypharmacy, long-acting injectable use or lifetime electroconvulsive therapy. The two proteins correlated strongly in patients (r = 0.900) and controls (r = 0.844), with no significant between-group difference in the correlation (Fisher r-to-z, p = 0.339), and neither tracked PANSS or CGI-S. Sex-stratified differences reached significance in women only, but the group × sex interaction was not significant.
Conclusions: Serum ANXA1 and neurogranin were lower in chronic schizophrenia and showed no statistically significant association with the treatment variables measured, although medication effects cannot be excluded in a uniformly medicated sample. Because no inflammatory, central or longitudinal measures were obtained, these exploratory findings cannot demonstrate impaired resolution of inflammation, altered central synaptic integrity, or trait status; they identify two candidate peripheral markers that require replication.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12888-026-08822-3.
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BibTeX
@article{sancaktar2026lower,
title = {{Lower serum annexin A1 and neurogranin levels in chronic schizophrenia: a case–control study}},
author = {Muhammet Sancaktar and Bahadır Demir and Ekin Nur Yağdıran and Gülçin Elboğa and Feridun Bülbül and Kenan Ercan and Seyithan Taysı and Abdurrahman Altındağ},
journal = {BMC Psychiatry},
year = {2026},
month = oct,
doi = {10.1186/s12888-026-08822-3},
url = {https://doi.org/10.1186/s12888-026-08822-3},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Lower serum annexin A1 and neurogranin levels in chronic schizophrenia: a case–control study
AU - Muhammet Sancaktar
AU - Bahadır Demir
AU - Ekin Nur Yağdıran
AU - Gülçin Elboğa
AU - Feridun Bülbül
AU - Kenan Ercan
AU - Seyithan Taysı
AU - Abdurrahman Altındağ
PY - 2026
DA - 2026/10/27
JO - BMC Psychiatry
DO - 10.1186/s12888-026-08822-3
UR - https://doi.org/10.1186/s12888-026-08822-3
AB - Background: Synaptic dysfunction and immune mechanisms are both implicated in schizophrenia. Annexin A1 (ANXA1) is a glucocorticoid-induced pro-resolving protein and neurogranin (Ng) is a post-synaptic, calmodulin-binding protein studied as a peripheral correlate of synaptic biology. Circulating ANXA1 has not previously been measured in schizophrenia, and serum Ng is sparsely characterised, so no directional hypothesis was pre-specified. Methods: In a single-centre case–control study, 35 patients meeting DSM-5 criteria for schizophrenia (diagnosed with the SCID-5) and 35 sex-comparable healthy controls were enrolled. Fasting serum ANXA1 and Ng were measured in duplicate by sandwich enzyme-linked immunosorbent assay. Symptom severity was rated with the PANSS and CGI-S, and antipsychotic treatment was documented including chlorpromazine equivalents. The pre-specified primary analysis was the Mann–Whitney U test for each biomarker, with Bonferroni and false-discovery-rate correction; group differences were then adjusted for age, sex and body-mass index by analysis of covariance. All other analyses were exploratory. Results: Both biomarkers were lower in patients: ANXA1 median 6.21 (IQR 5.12–8.34) vs. 13.06 (8.82–23.66) ng/mL (U = 309, p = 3.6 × 10⁻⁴; rank-biserial r = − 0.50) and Ng 174.2 (149.1–281.0) vs. 380.0 (237.1–547.1) pg/mL (U = 302, p = 2.7 × 10⁻⁴; r = − 0.51). Both remained significant after correction for multiple testing and in ANCOVA adjusted for age, sex and body-mass index (adjusted difference − 6.71 ng/mL, p = 0.011; −182.3 pg/mL, p = 0.0008). Neither biomarker was associated with chlorpromazine-equivalent dose, clozapine use, antipsychotic polypharmacy, long-acting injectable use or lifetime electroconvulsive therapy. The two proteins correlated strongly in patients (r = 0.900) and controls (r = 0.844), with no significant between-group difference in the correlation (Fisher r-to-z, p = 0.339), and neither tracked PANSS or CGI-S. Sex-stratified differences reached significance in women only, but the group × sex interaction was not significant. Conclusions: Serum ANXA1 and neurogranin were lower in chronic schizophrenia and showed no statistically significant association with the treatment variables measured, although medication effects cannot be excluded in a uniformly medicated sample. Because no inflammatory, central or longitudinal measures were obtained, these exploratory findings cannot demonstrate impaired resolution of inflammation, altered central synaptic integrity, or trait status; they identify two candidate peripheral markers that require replication. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12888-026-08822-3.
SN - 1471-244X
ER -