The Association of Serum Lactoferrin Level with Psychological Symptoms, Cognition, and Executive Function in Schizophrenia Patients
-
Niloufar Mahdavi Hazeveh
,
Soheila Kianpour Rad
,
Yousef Semnani
,
Maryam Mousavi Bazaz
,
Abdolreza Javadi
Abstract
Objective: Lactoferrin, a glycoprotein, has known neuroprotective effects, yet its role in the pathophysiology of neuropsychiatric disorders, particularly schizophrenia, remains unclear. This study aims to assess changes in lactoferrin levels during different phases of schizophrenia and explore its relationship with cognitive symptoms and performance.
Method: This before/after interventional study involved 30 patients diagnosed with schizophrenia. Participants were evaluated at two time points: upon hospital admission and after the resolution of acute symptoms. The Positive and Negative Syndrome Scale (PANSS) was utilized to measure symptom severity, while the Brief Assessment of Cognition in Schizophrenia (BACS) assessed the neurocognitive function. Serum lactoferrin levels were quantified using the Enzyme-Linked Immunosorbent Assay (ELISA) method.
Results: Serum lactoferrin levels significantly decreased from 130.63 ± 52.49 ng/mL at admission to 85.42 ± 29.03 ng/mL at discharge (P < 0.001). No significant correlation was found between lactoferrin levels and PANSS scores (r = 0.011, P = 0.975). However, an inverse correlation was observed between changes in lactoferrin levels and the executive function subscale of the BACS (r = -0.360, P = 0.050). Cognitive assessments indicated significant improvements in verbal memory (P = 0.033), working memory (P = 0.002), and executive function (P = 0.039) post-treatment.
Conclusion: The study demonstrates a significant reduction in serum lactoferrin levels during the acute phase of schizophrenia, suggesting its potential role in modulating cognitive functions, particularly the executive function, rather than influencing positive or negative symptoms.
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19. Rosa L, Cutone A, Lepanto MS, Paesano R, Valenti P. Lactoferrin: A Natural Glycoprotein Involved in Iron and Inflammatory Homeostasis. Int J Mol Sci. 2017;18(9):1985.
20. Cutone A, Ianiro G, Lepanto MS, Rosa L, Valenti P, Bonaccorsi di Patti MC, et al. Lactoferrin in the Prevention and Treatment of Intestinal Inflammatory Pathologies Associated with Colorectal Cancer Development. Cancers (Basel). 2020;12(12):3806.
21. He J, Furmanski P. Sequence specificity and transcriptional activation in the binding of lactoferrin to DNA. Nature. 1995;373(6516):721-4.
22. Miriyala S, Panchatcharam M, Ramanujam M, Puvanakrishnan R. A novel tetrapeptide derivative exhibits in vitro inhibition of neutrophil-derived reactive oxygen species and lysosomal enzymes release. Oxid Med Cell Longev. 2013;2013:853210.
23. Huang JM, Wang ZY, Ju ZH, Wang CF, Li QL, Sun T, et al. Two splice variants of the bovine lactoferrin gene identified in Staphylococcus aureus isolated from mastitis in dairy cattle. Genet Mol Res. 2011;10(4):3199-203.
24. Sacharczuk M, Zagulski T, Sadowski B, Barcikowska M, Pluta R. [Lactoferrin in the central nervous system]. Neurol Neurochir Pol. 2005;39(6):482-9.
25. Lemma SA, Kuusisto M, Haapasaari KM, Sormunen R, Lehtinen T, Klaavuniemi T, et al. Integrin alpha 10, CD44, PTEN, cadherin-11 and lactoferrin expressions are potential biomarkers for selecting patients in need of central nervous system prophylaxis in diffuse large B-cell lymphoma. Carcinogenesis. 2017;38(8):812-20.
26. Dadgar H, Majidi H, Aghaei S. Biological and Neurobiological Mechanisms of Transcranial Direct Current Stimulation. Iran J Psychiatry. 2022;17(3):350-5.
27. Mika A, Day HE, Martinez A, Rumian NL, Greenwood BN, Chichlowski M, et al. Early life diets with prebiotics and bioactive milk fractions attenuate the impact of stress on learned helplessness behaviours and alter gene expression within neural circuits important for stress resistance. Eur J Neurosci. 2017;45(3):342-57.
28. Ye X, Tai W, Zhang D. The early events of Alzheimer's disease pathology: from mitochondrial dysfunction to BDNF axonal transport deficits. Neurobiol Aging. 2012;33(6):1122.e1-10.
29. Jiménez-Jiménez FJ, Alonso-Navarro H, García-Martín E, Agúndez JAG. Biological fluid levels of iron and iron-related proteins in Parkinson's disease: Review and meta-analysis. Eur J Neurol. 2021;28(3):1041-55.
30. Leveugle B, Faucheux BA, Bouras C, Nillesse N, Spik G, Hirsch EC, et al. Cellular distribution of the iron-binding protein lactotransferrin in the mesencephalon of Parkinson's disease cases. Acta Neuropathol. 1996;91(6):566-72.
31. Tsatsanis A, McCorkindale AN, Wong BX, Patrick E, Ryan TM, Evans RW, et al. The acute phase protein lactoferrin is a key feature of Alzheimer's disease and predictor of Aβ burden through induction of APP amyloidogenic processing. Mol Psychiatry. 2021;26(10):5516-31.
32. An L, Sato H, Konishi Y, Walker DG, Beach TG, Rogers J, et al. Expression and localization of lactotransferrin messenger RNA in the cortex of Alzheimer's disease. Neurosci Lett. 2009;452(3):277-80.
2. Hosseini SA, Sepehrmanesh Z, Gilasi H, Ghoraishi FS. The Effect of Memantine Versus Folic Acid on Cognitive Impairment in Patients with Schizophrenia: A Randomized Clinical Trial. Iran J Psychiatry. 2023;18(3):258-65.
3. Dean B, Copolov D, Scarr E. Understanding the pathophysiology of schizophrenia: Contributions from the Melbourne Psychiatric Brain Bank. Schizophr Res. 2016;177(1-3):108-14.
4. Fe'li SN, Yassini Ardekani SM, Dehghani A. Relationship between Serum Homocysteine and Metabolic Syndrome among Patients with Schizophrenia and Bipolar Disorder: A Cross Sectional Study. Iran J Psychiatry. 2020;15(4):266-73.
5. Onitsuka T, Oribe N, Nakamura I, Kanba S. Review of neurophysiological findings in patients with schizophrenia. Psychiatry Clin Neurosci. 2013;67(7):461-70.
6. Buoli M, Serati M, Caldiroli A, Cremaschi L, Altamura AC. Neurodevelopmental Versus Neurodegenerative Model of Schizophrenia and Bipolar Disorder: Comparison with Physiological Brain Development and Aging. Psychiatr Danub. 2017;29(1):24-7.
7. Harrison PJ. On the neuropathology of schizophrenia and its dementia: neurodevelopmental, neurodegenerative, or both? Neurodegeneration. 1995;4(1):1-12.
8. Bora E. Neurodevelopmental origin of cognitive impairment in schizophrenia. Psychol Med. 2015;45(1):1-9.
9. Jiang S, Huang H, Zhou J, Li H, Duan M, Yao D, et al. Progressive trajectories of schizophrenia across symptoms, genes, and the brain. BMC Med. 2023;21(1):237.
10. Schirmbeck GH, Sizonenko S, Sanches EF. Neuroprotective Role of Lactoferrin during Early Brain Development and Injury through Lifespan. Nutrients. 2022;14(14):2923.
11. Naidu SAG, Wallace TC, Davies KJA, Naidu AS. Lactoferrin for Mental Health: Neuro-Redox Regulation and Neuroprotective Effects across the Blood-Brain Barrier with Special Reference to Neuro-COVID-19. J Diet Suppl. 2023;20(2):218-53.
12. Eker F, Bolat E, Pekdemir B, Duman H, Karav S. Lactoferrin: neuroprotection against Parkinson's disease and secondary molecule for potential treatment. Front Aging Neurosci. 2023;15:1204149.
13. Li YQ, Guo C. A Review on Lactoferrin and Central Nervous System Diseases. Cells. 2021;10(7):1810.
14. Yong SJ, Veerakumarasivam A, Lim WL, Chew J. Neuroprotective Effects of Lactoferrin in Alzheimer's and Parkinson's Diseases: A Narrative Review. ACS Chem Neurosci. 2023.
15. Hällgren R, Venge P, Wistedt B. Elevated serum levels of lactoferrin and eosinophil cationic protein in schizophrenic patients. Br J Psychiatry. 1982;140:55-60.
16. Ghamari Givi H, Moulavi P, Heshmati R. Exploration of the factor structure of positive and negative syndrome scale in schizophernia spectrum disorder. J Clin Psychol. 2010;2(2):1-10.
17. Keefe RS, Goldberg TE, Harvey PD, Gold JM, Poe MP, Coughenour L. The Brief Assessment of Cognition in Schizophrenia: reliability, sensitivity, and comparison with a standard neurocognitive battery. Schizophr Res. 2004;68(2-3):283-97.
18. Mazhari S, Parvaresh N, Eslami Shahrbabaki M, Sadeghi MM, Nakhaee N, Keefe RS. Validation of the Persian version of the brief assessment of cognition in schizophrenia in patients with schizophrenia and healthy controls. Psychiatry Clin Neurosci. 2014;68(2):160-6.
19. Rosa L, Cutone A, Lepanto MS, Paesano R, Valenti P. Lactoferrin: A Natural Glycoprotein Involved in Iron and Inflammatory Homeostasis. Int J Mol Sci. 2017;18(9):1985.
20. Cutone A, Ianiro G, Lepanto MS, Rosa L, Valenti P, Bonaccorsi di Patti MC, et al. Lactoferrin in the Prevention and Treatment of Intestinal Inflammatory Pathologies Associated with Colorectal Cancer Development. Cancers (Basel). 2020;12(12):3806.
21. He J, Furmanski P. Sequence specificity and transcriptional activation in the binding of lactoferrin to DNA. Nature. 1995;373(6516):721-4.
22. Miriyala S, Panchatcharam M, Ramanujam M, Puvanakrishnan R. A novel tetrapeptide derivative exhibits in vitro inhibition of neutrophil-derived reactive oxygen species and lysosomal enzymes release. Oxid Med Cell Longev. 2013;2013:853210.
23. Huang JM, Wang ZY, Ju ZH, Wang CF, Li QL, Sun T, et al. Two splice variants of the bovine lactoferrin gene identified in Staphylococcus aureus isolated from mastitis in dairy cattle. Genet Mol Res. 2011;10(4):3199-203.
24. Sacharczuk M, Zagulski T, Sadowski B, Barcikowska M, Pluta R. [Lactoferrin in the central nervous system]. Neurol Neurochir Pol. 2005;39(6):482-9.
25. Lemma SA, Kuusisto M, Haapasaari KM, Sormunen R, Lehtinen T, Klaavuniemi T, et al. Integrin alpha 10, CD44, PTEN, cadherin-11 and lactoferrin expressions are potential biomarkers for selecting patients in need of central nervous system prophylaxis in diffuse large B-cell lymphoma. Carcinogenesis. 2017;38(8):812-20.
26. Dadgar H, Majidi H, Aghaei S. Biological and Neurobiological Mechanisms of Transcranial Direct Current Stimulation. Iran J Psychiatry. 2022;17(3):350-5.
27. Mika A, Day HE, Martinez A, Rumian NL, Greenwood BN, Chichlowski M, et al. Early life diets with prebiotics and bioactive milk fractions attenuate the impact of stress on learned helplessness behaviours and alter gene expression within neural circuits important for stress resistance. Eur J Neurosci. 2017;45(3):342-57.
28. Ye X, Tai W, Zhang D. The early events of Alzheimer's disease pathology: from mitochondrial dysfunction to BDNF axonal transport deficits. Neurobiol Aging. 2012;33(6):1122.e1-10.
29. Jiménez-Jiménez FJ, Alonso-Navarro H, García-Martín E, Agúndez JAG. Biological fluid levels of iron and iron-related proteins in Parkinson's disease: Review and meta-analysis. Eur J Neurol. 2021;28(3):1041-55.
30. Leveugle B, Faucheux BA, Bouras C, Nillesse N, Spik G, Hirsch EC, et al. Cellular distribution of the iron-binding protein lactotransferrin in the mesencephalon of Parkinson's disease cases. Acta Neuropathol. 1996;91(6):566-72.
31. Tsatsanis A, McCorkindale AN, Wong BX, Patrick E, Ryan TM, Evans RW, et al. The acute phase protein lactoferrin is a key feature of Alzheimer's disease and predictor of Aβ burden through induction of APP amyloidogenic processing. Mol Psychiatry. 2021;26(10):5516-31.
32. An L, Sato H, Konishi Y, Walker DG, Beach TG, Rogers J, et al. Expression and localization of lactotransferrin messenger RNA in the cortex of Alzheimer's disease. Neurosci Lett. 2009;452(3):277-80.
| Files | ||
| Issue | Vol 20 No 1 (2025) | |
| Section | Original Article(s) | |
| Keywords | ||
| Cognitive Dysfunction Lactoferrin Neurodegenerative Diseases Schizophrenia Neuropsychiatric Disorder | ||
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How to Cite
1.
Mahdavi Hazeveh N, Kianpour Rad S, Semnani Y, Mousavi Bazaz M, Javadi A. The Association of Serum Lactoferrin Level with Psychological Symptoms, Cognition, and Executive Function in Schizophrenia Patients. Iran J Psychiatry. 2024;20(1):20-26.
