Serum Levels of C-Reactive Protein, Albumin and CRP–Albumin Ratio in Patients with Major Mental Illnesses
DOI:
https://doi.org/10.51152/jbarbiomed.v12i1.265Keywords:
Acute phase protein, Bipolar disorder, CRP-albumin ratio, InflammationAbstract
Background: Increasing evidence implicates immune dysregulation and chronic low-grade systemic inflammation in the pathophysiology and clinical progression of major mental illnesses (MMIs). Elevated levels of acute-phase proteins, pro-inflammatory cytokines, and adhesion molecules have been reported in patients with MMI however, comparative data on differential alterations in inflammatory markers among Nigerians with schizophrenia, bipolar disorder, and depression remain limited.
Objectives: To determine the serum levels of C-reactive protein (CRP), albumin, and CRP–albumin ratio (CAR) in patients with MMI.
Methods: Eighty-six participants were enrolled in this comparative cross-sectional study. They comprised 47 patients with MMIs (18 with schizophrenia, 15 with bipolar disorder and 14 with depression) who were on antipsychotics, and 39 apparently healthy controls. Serum levels of CRP and albumin were determined using semi-quantitative agglutination method and Bromocresol green method, respectively. Thereafter, the CRP-albumin ratio (CAR) was calculated as appropriate.
Results: The mean serum levels of CRP, albumin and CAR did not differ significantly between patients with MMI and controls. However, stratified analyses revealed slightly elevated CRP levels in patients with bipolar disorder compared with those with schizophrenia and depression. Significant inverse correlations were observed between albumin and CAR in patients with depression, bipolar disorder and schizophrenia. Also, CRP showed significant positive correlation with CAR in both the bipolar disorder and schizophrenia groups.
Conclusion: Trends towards differential inflammatory alterations were observed among patients with major mental illnesses, with changes appearing more pronounced in bipolar disorder despite ongoing antipsychotic therapy.
References
Oluwasanya, A. N., Adekunle, W. A., et al. (2025). Mental health care services in Nigeria: A qualitative enquiry from family physicians' perspective. PLOS Mental Health, 2(9), e0000285. https://doi.org/10.1371/journal.pmen.0000285
Akinlade, K. S., Adedokun, K., Rahamon, S., & Lasebikan, V. (2020). Elevated levels of visfatin and fetuin-a in patients with major mental disorders. Archives of Basic and Applied Medicine, 8(1), 49-53.
Akinlade, K. S., Ofagbor, E., Rahamon, S., & Lasebikan, V. (2019). Effect of adiposity and type of antipsychotic medication on plasma levels of resistin and adiponectin in patients with major mental illnesses. African Journal of Biomedical Research, 22(3), 235-239.
Al-Marwani, S., Batieha, A., Khader, Y., El-Khateeb, M., Jaddou, H., & Ajlouni, K. (2023). Association between albumin and depression: A population-based study. BMC Psychiatry, 23(1), 780. https://doi.org/10.1186/s12888-023-05174-0
Balcioglu, Y. H., & Kirlioglu, S. S. (2020). C-reactive protein/albumin and neutrophil/albumin ratios as novel inflammatory markers in patients with schizophrenia. Psychiatry Investigation, 17(9), 902-910. https://doi.org/10.30773/pi.2020.0185
Bauer, M. E., & Teixeira, A. L. (2019). Inflammation in psychiatric disorders: What comes first? Annals of the New York Academy of Sciences, 1437(1), 57-67. https://doi.org/10.1111/nyas.13712
Chen, S., Xia, H. S., Zhu, F., Yin, G. Z., Qian, Z. K., Jiang, C. X., et al. (2018). Association between decreased serum albumin levels and depressive symptoms in patients with schizophrenia in a Chinese Han population: A pilot study. Psychiatry Research, 270, 438-442. https://doi.org/10.1016/j.psychres.2018.10.012
Dean, B. (2011). Understanding the role of inflammatory-related pathways in the pathophysiology and treatment of psychiatric disorders: Evidence from human peripheral studies and CNS studies. International Journal of Neuropsychopharmacology, 14(7), 997-1012. https://doi.org/10.1017/s1461145710001410
Dregan, A., Matcham, F., Harber-Aschan, L., Rayner, L., Brailean, A., Davis, K., et al. (2019). Common mental disorders within chronic inflammatory disorders: A primary care database prospective investigation. Annals of the Rheumatic Diseases, 78(5), 688-695. https://doi.org/10.1136/annrheumdis-2018-214676
Evers, A. K., Veeh, J., McNeill, R., Reif, A., & Kittel-Schneider, S. (2019). C-reactive protein concentration in bipolar disorder: Association with genetic variants. International Journal of Bipolar Disorders, 7(1), 26. https://doi.org/10.1186/s40345-019-0162-z
Figueroa-Hall, L. K., Xu, B., Kuplicki, R., Ford, B. N., Burrows, K., Teague, T. K., et al. (2022). Psychiatric symptoms are not associated with circulating CRP concentrations after controlling for medical, social, and demographic factors. Translational Psychiatry, 12(1), 279. https://doi.org/10.1038/s41398-022-02049-y
First, M. B., & Gibbon, M. (2004). The Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) and the Structured Clinical Interview for DSM-IV Axis II Disorders (SCID-II). In M. J. Hilsenroth & D. L. Segal (Eds.), Comprehensive handbook of psychological assessment, Vol. 2. Personality assessment (pp. 134–143). John Wiley & Sons, Inc.
Fond, G. (2014). Inflammation in psychiatric disorders. European Psychiatry, 29(S3), 551-552.
GBD 2023 Mental Disorder Collaborators. (2026). Updated trends in the global prevalence and burden of mental disorders, 1990-2023: A systematic analysis for the Global Burden of Disease Study 2023. Lancet, 407(10543), 2040-2064. https://doi.org/10.1016/s0140-6736(26)00519-2
Generoso, J. S., Giridharan, V. V., Lee, J., Macedo, D., & Barichello, T. (2021). The role of the microbiota-gut-brain axis in neuropsychiatric disorders. Brazilian Journal of Psychiatry, 43(3), 293-305. https://doi.org/10.1590/1516-4446-2020-0987
Howren, M. B., Lamkin, D. M., & Suls, J. (2009). Associations of depression with C-reactive protein, IL-1, and IL-6: A meta-analysis. Psychosomatic Medicine, 71(2), 171-186. https://doi.org/10.1097/PSY.0b013e3181907c1b
Juncal-Ruiz, M., Riesco-Dávila, L., Ortiz-García de la Foz, V., Martínez-Garcia, O., Ramírez-Bonilla, M., Ocejo-Viñals, J. G., et al. (2018). Comparison of the anti-inflammatory effect of aripiprazole and risperidone in 75 drug-naïve first episode psychosis individuals: A 3 months randomized study. Schizophrenia Research, 202, 226-233. https://doi.org/10.1016/j.schres.2018.06.039
Maes, M., Wauters, A., Neels, H., Scharpé, S., Van Gastel, A., D'Hondt, P., et al. (1995). Total serum protein and serum protein fractions in depression: Relationships to depressive symptoms and glucocorticoid activity. Journal of Affective Disorders, 34(1), 61-69. https://doi.org/10.1016/0165-0327(94)00106-j
McFarland, D. C., Breitbart, W., Miller, A. H., & Nelson, C. (2020). Depression and inflammation in patients with lung cancer: A comparative analysis of acute phase reactant inflammatory markers. Psychosomatics, 61(5), 527-537. https://doi.org/10.1016/j.psym.2020.03.005
Miller, B. J., Culpepper, N., & Rapaport, M. H. (2014). C-reactive protein levels in schizophrenia: A review and meta-analysis. Clinical Schizophrenia & Related Psychoses, 7(4), 223-230.
Nicholas, A., Joshua, O., & Elizabeth, O. (2022). Accessing mental health services in africa: Current state, efforts, challenges and recommendation. Annals of Medicine and Surgery, 81, 104421. https://doi.org/10.1016/j.amsu.2022.104421
Olgun Yazar, H., Yazar, T., Özdemir, S., & Kasko Arici, Y. (2019). Serum C-reactive protein/albumin ratio and restless legs syndrome. Sleep Medicine, 58, 61-65. https://doi.org/10.1016/j.sleep.2019.02.022
Orsolini, L., Pompili, S., Tempia Valenta, S., Salvi, V., & Volpe, U. (2022). C-reactive protein as a biomarker for major depressive disorder? International Journal of Molecular Sciences, 23(3), 1616. https://doi.org/10.3390/ijms23031616
Palmos, A. B., Hübel, C., Lim, K. X., Hunjan, A. K., Coleman, J. R. I., & Breen, G. (2023). Assessing the evidence for causal associations between body mass index, C-reactive protein, depression, and reported trauma using Mendelian randomization. Biological Psychiatry Global Open Science, 3(1), 110-118. https://doi.org/10.1016/j.bpsgos.2022.01.003
Pitharouli, M. C., Hagenaars, S. P., Glanville, K. P., Coleman, J. R. I., Hotopf, M., Lewis, C. M., et al. (2021). Elevated C-reactive protein in patients with depression, independent of genetic, health, and psychosocial factors: Results from the UK Biobank. American Journal of Psychiatry, 178(6), 522-529. https://doi.org/10.1176/appi.ajp.2020.20060947
Ranzani, O. T., Zampieri, F. G., Forte, D. N., Azevedo, L. C., & Park, M. (2013). C-reactive protein/albumin ratio predicts 90-day mortality of septic patients. PLOS One, 8(3), e59321. https://doi.org/10.1371/journal.pone.0059321
Sayed, M. M., Gaafary, M. M. E., Elsheikh, M. M. E., Hamed, S. S., Mohamed, R. M. A., & Aboutaleb, M. Y. M. (2025). Serum albumin level in a sample of Egyptian patients with major depressive and bipolar disorders; a case control comparative study. Middle East Current Psychiatry, 32(1), 56.
Sethi, R., Gómez-Coronado, N., Walker, A. J., Robertson, O. D., Agustini, B., Berk, M., et al. (2019). Neurobiology and therapeutic potential of cyclooxygenase-2 (COX-2) inhibitors for inflammation in neuropsychiatric disorders. Frontiers in Psychiatry, 10, 605. https://doi.org/10.3389/fpsyt.2019.00605
Sobiś, J., Rykaczewska-Czerwińska, M., Świętochowska, E., & Gorczyca, P. (2015). Therapeutic effect of aripiprazole in chronic schizophrenia is accompanied by anti-inflammatory activity. Pharmacological Reports, 67(2), 353-359. https://doi.org/10.1016/j.pharep.2014.09.007
Van Hunsel, F., Wauters, A., Vandoolaeghe, E., Neels, H., Demedts, P., & Maes, M. (1996). Lower total serum protein, albumin, and beta- and gamma-globulin in major and treatment-resistant depression: Effects of antidepressant treatments. Psychiatry Research, 65(3), 159-169. https://doi.org/10.1016/s0165-1781(96)03010-7
WHO. (2025). Mental disorders. Retrieved 20 May 2026, from https://www.who.int/news-room/fact-sheets/detail/mental-disorders
Xu, H., Zheng, L., Wang, L., Gao, H., Wei, Y., & Chen, J. (2023). Albumin and associated biomarkers in severe neuropsychiatric disorders: Acute-phase schizophrenia and bipolar disorder. Neuropsychiatric Disease and Treatment, 19, 2027-2037. https://doi.org/10.2147/ndt.s423399
Yazar, H. O., Yazar, T., Aygün, A., Kaygisiz, Ş., & Kirbaş, D. (2020). Evaluation of simple inflammatory blood parameters in patients with migraine. Irish Journal of Medical Science, 189(2), 677-683. https://doi.org/10.1007/s11845-019-02136-y
Yazar, T., & Yazar, H. O. (2019). Evaluation of C-reactive protein/albumin ratio according to stage in patients with idiopathic parkinson disease. Turkish Journal of Neurology, 25(3), 123-128.
Yuan, N., Chen, Y., Xia, Y., Dai, J., & Liu, C. (2019). Inflammation-related biomarkers in major psychiatric disorders: A cross-disorder assessment of reproducibility and specificity in 43 meta-analyses. Translational Psychiatry, 9(1), 233. https://doi.org/10.1038/s41398-019-0570-y
Zhang, G., Li, S., Wang, S., Deng, F., Sun, X., & Pan, J. (2023). The association between serum albumin and depressive symptoms: A cross-sectional study of NHANES data during 2005-2018. BMC Psychiatry, 23(1), 448. https://doi.org/10.1186/s12888-023-04935-1
Additional Files
Published
Data Availability Statement
The data supporting the findings of this study are included within the article and its supplementary materials.Issue
Section
License
Copyright (c) 2026 Sheu Kadiri Rahamon, Dorcas Damilola Olubunmi, Olusola Oladipo Adekola, Victor Olufolahan Lasebikan
This work is licensed under a Creative Commons Attribution 4.0 International License.
