Serum CRP, vitamin D, and ferritin levels in male inpatients with schizophrenia spectrum disorders and bipolar mania: a retrospective analysis of clinical correlates

Hatice Ayça Kaloğlu; İlke İşler; Yasir Şafak

Serum CRP, vitamin D, and ferritin levels in male inpatients with schizophrenia spectrum disorders and bipolar mania: a retrospective analysis of clinical correlates

Abstract

Aims: Schizophrenia spectrum disorders and bipolar mania share neurobiological mechanisms, yet conventional diagnostic categories often fail to explain clinical heterogeneity. This study investigated whether peripheral biomarkers-C-reactive protein (CRP), 25-hydroxyvitamin D [25(OH)D], and ferritin-could identify biologically meaningful subgroups and predict short-term treatment outcomes within a precision psychiatry framework. Methods: A retrospective review of 139 males inpatients (101 with schizophrenia spectrum, 38 with bipolar mania) was conducted. Serum CRP, 25(OH)D, and ferritin levels were measured within 24 hours of admission. Clinical outcomes were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Young Mania Rating Scale (YMRS). Hierarchical regression analyses, adjusted for variables such as age, smoking, and clozapine use, examined the associations between baseline biomarkers and clinical trajectory. Results: No significant differences in biomarker levels were found between diagnostic groups. However, within the schizophrenia group, lower 25(OH)D levels were associated with greater admission severity and remained independently associated with higher discharge PANSS negative symptom scores. In the bipolar mania group, higher baseline CRP independently predicted a lower percentage of improvement in YMRS scores during hospitalization. Ferritin and CRP correlations with admission severity did not survive adjusted analyses. Conclusion: While peripheral biomarkers did not distinguish between the two diagnoses, they served as significant prognostic indicators. Specifically, vitamin D levels related to negative symptom burden in schizophrenia, while CRP predicted poorer short-term improvement in bipolar mania. These findings suggest that peripheral biomarkers are more valuable as adjunctive measures for predicting clinical course rather than as standalone diagnostic tools.

Keywords

References

Dines M, Kes M, Ailán D, et al. Bipolar disorders and schizophrenia: discrete disorders? Front Psychiatry. 2024;15:1352250. doi:10.3389/fpsyt.2024.1352250
Owen MJ, Sawa A, Mortensen PB. Schizophrenia. Lancet. 2016; 388(10039):86-97. doi:10.1016/S0140-6736(15)00742-9
Fernandes BS, Williams LM, Steiner J, et al. The new field of 'precision psychiatry'. BMC Med. 2017;15(1):80. doi:10.1186/s12916-017-0849-x
Abi-Dargham A, Moeller SJ, Ali F, et al. Candidate biomarkers in psychiatric disorders: state of the field. World Psychiatry. 2023;22(2):236-262. doi:10.1002/wps.21078
Khandaker GM, Dantzer R. Is there a role for immune-to-brain communication in schizophrenia? Psychopharmacology (Berl). 2016; 233(9):1559-1573. doi:10.1007/s00213-015-3975-1
McCutcheon RA, Reis Marques T, Howes OD. Schizophrenia-an overview. JAMA Psychiatry. 2020;77(2):201-210. doi:10.1001/jamapsychiatry.2019.3360
Pinzi M, Fagiolini A, Koukouna D, et al. Inflammatory and immune biomarkers in mood disorders: from mechanistic pathways to clinical translation. Cells. 2025;14(19):1558. doi:10.3390/cells14191558
Miller BJ, Culpepper N, Rapaport MH. C-reactive protein levels in schizophrenia: a review and meta-analysis. Clin Schizophr Relat Psychoses. 2014;7(4):223-230. doi:10.3371/CSRP.MICU.020813

Cui X, McGrath JJ, Burne THJ, Eyles DW. Vitamin D and schizophrenia: 20 years on. Mol Psychiatry. 2021;26(7):2708-2720. doi:10.1038/s41380-021-01025-0
Beard JL. Iron biology in immune function, muscle metabolism and neuronal functioning. J Nutr. 2001;131(2):568S-579S. doi:10.1093/jn/131.2.568S
Goldsmith DR, Rapaport MH, Miller BJ. A meta-analysis of blood cytokine network alterations in psychiatric patients: comparisons between schizophrenia, bipolar disorder and depression. Mol Psychiatry. 2016;21(12):1696-1709. doi:10.1038/mp.2016.3
American Psychiatric Association. *Diagnostic and Statistical Manual of Mental Disorders: DSM-5-TR. 5th ed, text rev. American Psychiatric Association Publishing; 2022.
Tabachnick BG, Fidell LS. Using multivariate statistics. 6th ed. Pearson; 2013.
Giménez-Palomo A, Andreu H, Olivier L, et al. Clinical, sociodemographic and environmental predicting factors for relapse in bipolar disorder: a systematic review. J Affect Disord. 2024;360:276-296. doi:10.1016/j.jad.2024.05.064
Grande I, Berk M, Birmaher B, Vieta E. Bipolar disorder. Lancet. 2016; 387(10027):1561-1572. doi:10.1016/S0140-6736(15)00241-4
Valipour G, Saneei P, Esmaillzadeh A. Serum vitamin D levels in relation to schizophrenia: a systematic review and meta-analysis of observational studies. J Clin Endocrinol Metab. 2014;99(10):3863-3874. doi:10.1210/jc.2014-1887
Adamson J, Lally J, Gaughran F, et al. Correlates of vitamin D in psychotic disorders: a comprehensive systematic review. Psychiatry Res. 2017;249:78-90. doi:10.1016/j.psychres.2016.12.051
Aras N, Yılmaz H, Ucuncu O. The psychotropic effect of vitamin D supplementation on schizophrenia symptoms. BMC Psychiatry. 2021; 21(1):309. doi:10.1186/s12888-021-03310-x
Eyles DW, Smith S, Kinobe R, et al. Distribution of the vitamin D receptor and 1 alpha-hydroxylase in human brain. J Chem Neuroanat. 2005;29(1):21-30. doi:10.1016/j.jchemneu.2004.08.006
Kesby JP, Eyles DW, Burne TH, McGrath JJ. The effects of vitamin D on brain development and adult brain function. Mol Cell Endocrinol. 2011; 347(1-2):121-127. doi:10.1016/j.mce.2011.05.014
Chen S, Tan Y, Tian L. Immunophenotypes in psychosis: is it a premature inflamm-aging disorder? Mol Psychiatry. 2024;29(9):2834-2848. doi: 10.1038/s41380-024-02539-z
Segarceanu LM, Zanfir AG, Minca DG, Trifu S. Evaluation of inflammatory markers in perception disorders in major psychiatric pathology. Int J Mol Sci. 2025;26(19):9299. doi:10.3390/ijms26199299
Heil M, Edlinger M, Biedermann F, et al. Changes in psychopathology and peripheral inflammation in schizophrenia patients initiating treatment with second-generation antipsychotics: a post-hoc analysis. Front Psychiatry. 2025;16:1644428. doi:10.3389/fpsyt.2025.1644428
Ramos MA, Hernández C, Arranz B. Iron dysregulation across the schizophrenia lifespan: a systematic review from prenatal risk to postmortem findings. Psychiatry Res. 2026;362:117193. doi: 10.1016/j.psychres.2026.117193
Yehia A, Melhuish Beaupre LM, Ho MC, Biernacka JM, Frye MA, Abulseoud OA. Ferroptosis as a potential molecular mechanism of bipolar disorder. Transl Psychiatry. 2025;15(1):205. doi: 10.1038/s41398-025-03429-w
Munkholm K, Jacoby AS, Vinberg M, Kessing LV. Ferritin as a potential disease marker in patients with bipolar disorder. J Affect Disord. 2023; 332:247-253. doi: 10.1016/j.jad.2023.04.006
Lotan A, Luza S, Opazo CM, et al. Perturbed iron biology in the prefrontal cortex of people with schizophrenia. Mol Psychiatry. 2023; 28(5):2058-2070. doi:10.1038/s41380-023-01979-3
Levin SW, Gattari TB. Iron deficiency in psychiatric patients. Curr Psychiatr. 2023;22(3):25-30.
Fernandes BS, Steiner J, Molendijk ML, et al. C-reactive protein concentrations across the mood spectrum in bipolar disorder: a systematic review and meta-analysis. Lancet Psychiatry. 2016;3(12):1147-1156. doi:10.1016/S2215-0366(16)30370-4
Cuomo A, Koukouna D, Spiti A, et al. Biomarkers, inflammation, and bipolar disorder: association between the improvement of bipolar disorder severity and the improvement in C-reactive protein levels after 7 days of inpatient treatment. Front Psychiatry. 2021;12:803034. doi:10.3389/fpsyt.2021.803034
Poletti S, Mazza MG, Benedetti F. Inflammatory mediators in major depression and bipolar disorder. Transl Psychiatry. 2024;14(1):247. doi:10.1038/s41398-024-02921-z
Fuentes-Claramonte P, Estradé A, Solanes A, et al. Biomarkers for psychosis: are we there yet? Umbrella review of 1478 biomarkers. Schizophr Bull Open. 2024;5(1):sgae018. doi:10.1093/schizbullopen/sgae018
Etkin A, O'Donnell P, Ressler KJ, Manji H. Towards precision psychiatry: initial foundations and future directions. Nat Rev Drug Discov. Published online August 24, 2026. doi:10.1038/s41573-026-01509-0

Details

Primary Language

English

Subjects

Psychiatry

Journal Section

Research Article

Authors

Hatice Ayça Kaloğlu ^*
0000-0002-9457-5985
Türkiye

İlke İşler
0009-0007-4922-6755
Türkiye

Yasir Şafak
0000-0002-3531-3280
Türkiye

Publication Date

October 25, 2026

Submission Date

July 6, 2026

Acceptance Date

September 27, 2026

Published in Issue

Year 2026 Volume: 8 Number: 6

IZ

https://izlik.org/JA65GC24JW

Cite

RIS / Bibtex

APA

Kaloğlu, H. A., İşler, İ., & Şafak, Y. (2026). Serum CRP, vitamin D, and ferritin levels in male inpatients with schizophrenia spectrum disorders and bipolar mania: a retrospective analysis of clinical correlates. Anatolian Current Medical Journal, 8(6), 1331-1339. https://izlik.org/JA65GC24JW

AMA

1.Kaloğlu HA, İşler İ, Şafak Y. Serum CRP, vitamin D, and ferritin levels in male inpatients with schizophrenia spectrum disorders and bipolar mania: a retrospective analysis of clinical correlates. Anatolian Curr Med J / ACMJ / acmj. 2026;8(6):1331-1339. https://izlik.org/JA65GC24JW

Chicago

Kaloğlu, Hatice Ayça, İlke İşler, and Yasir Şafak. 2026. “Serum CRP, Vitamin D, and Ferritin Levels in Male Inpatients With Schizophrenia Spectrum Disorders and Bipolar Mania: A Retrospective Analysis of Clinical Correlates”. Anatolian Current Medical Journal 8 (6): 1331-39. https://izlik.org/JA65GC24JW.

EndNote

Kaloğlu HA, İşler İ, Şafak Y (October 1, 2026) Serum CRP, vitamin D, and ferritin levels in male inpatients with schizophrenia spectrum disorders and bipolar mania: a retrospective analysis of clinical correlates. Anatolian Current Medical Journal 8 6 1331–1339.

IEEE

[1]H. A. Kaloğlu, İ. İşler, and Y. Şafak, “Serum CRP, vitamin D, and ferritin levels in male inpatients with schizophrenia spectrum disorders and bipolar mania: a retrospective analysis of clinical correlates”, Anatolian Curr Med J / ACMJ / acmj, vol. 8, no. 6, pp. 1331–1339, Oct. 2026, [Online]. Available: https://izlik.org/JA65GC24JW

ISNAD

Kaloğlu, Hatice Ayça - İşler, İlke - Şafak, Yasir. “Serum CRP, Vitamin D, and Ferritin Levels in Male Inpatients With Schizophrenia Spectrum Disorders and Bipolar Mania: A Retrospective Analysis of Clinical Correlates”. Anatolian Current Medical Journal 8/6 (October 1, 2026): 1331-1339. https://izlik.org/JA65GC24JW.

JAMA

1.Kaloğlu HA, İşler İ, Şafak Y. Serum CRP, vitamin D, and ferritin levels in male inpatients with schizophrenia spectrum disorders and bipolar mania: a retrospective analysis of clinical correlates. Anatolian Curr Med J / ACMJ / acmj. 2026;8:1331–1339.

MLA

Kaloğlu, Hatice Ayça, et al. “Serum CRP, Vitamin D, and Ferritin Levels in Male Inpatients With Schizophrenia Spectrum Disorders and Bipolar Mania: A Retrospective Analysis of Clinical Correlates”. Anatolian Current Medical Journal, vol. 8, no. 6, Oct. 2026, pp. 1331-9, https://izlik.org/JA65GC24JW.

Vancouver

1.Hatice Ayça Kaloğlu, İlke İşler, Yasir Şafak. Serum CRP, vitamin D, and ferritin levels in male inpatients with schizophrenia spectrum disorders and bipolar mania: a retrospective analysis of clinical correlates. Anatolian Curr Med J / ACMJ / acmj [Internet]. 2026 Oct. 1;8(6):1331-9. Available from: https://izlik.org/JA65GC24JW