Association of Serum Cortisol, Interleukin-6, and Serotonin with Depression
Authors
Ayesha Tariq
University of Health Sciences, Lahore
Farhat Bano
University of Health Sciences, Lahore
Muhammad Haroon Khattak
CMH / Sheikh Khalifa Bin Zayed Al Nahyan Hospital, Muzaffarabad
Muhammad Azhar Sattar
Kuwait National Guard Hospital, Kuwait
Nasir Wakeel
Quaid-e-Azam Medical College, Bahawalpur
Aasma Tariq
Bahawal Victoria Hospital, Bahawalpur
Shabbir Hussain
University of Health Sciences, Lahore
Keywords
Depression, Cortisol, Interleukin-6, Serotonin, Biomarkers
Abstract
Objective: To explore the relation between serum cortisol, interleukin-6 (IL-6), and serotonin (5-HT) levels in patients with melancholic depression, atypical depression, and healthy controls.
Methodology: This cross-sectional comparative study was conducted from August 2023 to July 2024 at the Combined Military Hospital, Muzaffarabad. After ethical approval of the study, a total of 105 participants were enrolled using a non-probability convenience sampling method, including 35 healthy individuals, 35 with melancholic depression, and 35 with atypical depression. Serum levels of cortisol, IL-6, and serotonin were measured using enzyme-linked immunosorbent assay. The Statistical Package for the Social Sciences (SPSS) version 25 was used to analyze the data and determine associations between these biomarkers across different depression groups.
Results: Elevated serum IL-6 levels were found in both depression groups compared to healthy controls (p <0.001). Serum cortisol levels were significantly higher in both depression groups as compared to controls, with a notable difference between the two depression types (p <0.001). Serum serotonin levels were lower in both depression groups as compared to controls with no significant variation between melancholic and atypical depression (p <0.001). Positive correlations were observed between serum IL-6 and cortisol (p =0.001; r=0.629) in melancholic depression, while IL-6 exhibited a negative correlation with serotonin (p =0.014; r= -0.411) in atypical depression. Serum cortisol also displayed a negative correlation with serotonin in melancholic depression but the results were statistically insignificant (r=-0.33, p= 0.05).
Conclusion: This study revealed elevated cortisol & interleukin-6 levels and decreased serotonin levels in depression groups as compared to healthy controls. The melancholic & atypical depression subtypes did not significantly differ for interleukin-6 and serotonin levels. However, a significant elevation in serum cortisol levels was observed in patients with melancholic depression versus those with atypical depression.
References
- World Health Organization. Depressive disorder (depression). Geneva: WHO; 2023. Available from: https://www.who.int/news-room/fact-sheets/detail/depression.
- Greenberg PE, Fournier AA, Sisitsky T, Simes M, Berman R, Koenigsberg SH, et al. The economic burden of adults with major depressive disorder in the United States (2010 and 2018). Pharmacoeconomics. 2021; 39(6):653-65. doi:10.1007/s40273-021-01019-4.
- Orsolini L, Latini R, Pompili M, Serafini G, Volpe U, Vellante F, et al. Understanding the complex of suicide in depression: from research to clinics. Psychiatry Investig. 2020; 17(3):207-21. doi:10.30773/pi.2019.0171.
- Gold PW. Endocrine factors in key structural and intracellular changes in depression. Trends Endocrinol Metab. 2021; 32(4):212-23. doi:10.1016/j.tem.2021.01.003.
- Sameed S, Panicker MJ, Mendonsa RD, Kakunje A, Karkal R. Clinical, cognitive, and sociodemographic variables in melancholic versus nonmelancholic depression. Soc Health Behav. 2020; 3(3):103-9. doi:10.4103/SHB.SHB_28_20.
- Aguayo F. Male depression and its symptoms: a qualitative study with Chilean adult men. Salud Colect. 2022; 18:e3942. doi:10.18294/sc.2022.3942.
- Xu P, Sun Y. Risk factors for suicidal attempt in patients with the melancholic subtype of depressive disorder: implication for nursing care. Medicine (Baltimore). 2022; 101(32):e29713. doi:10.1097/MD.0000000000029713.
- Lu W, Zhang H, Zhou R, Ding L, Wang Y, Su Y, et al. Differences in cognitive functions of atypical and non-atypical depression based on propensity score matching. J Affect Disord. 2023; 325:732-8. doi:10.1016/j.jad.2023.01.071.
- Abi-Dargham A, Moeller SJ, Ali F, DeLorenzo C, Domschke K, Horga G, et al. Candidate biomarkers in psychiatric disorders: state of the field. World Psychiatry. 2023; 22(2):236-62. doi:10.1002/wps.21078.
- Sathyasaikumar KV, Notarangelo FM, Kelly DL, Rowland LM, Hare SM, Chen S, et al. Tryptophan challenge in healthy controls and people with schizophrenia: acute effects on plasma levels of kynurenine, kynurenic acid and 5-hydroxyindoleacetic acid. Pharmaceuticals (Basel). 2022; 15(8):1003. doi:10.3390/ph15081003.
- P S, Vellapandian C. Hypothalamic-pituitary-adrenal (HPA) axis: unveiling the potential mechanisms involved in stress-induced Alzheimer’s disease and depression. Cureus. 2024; 16(8):e67595. doi:10.7759/cureus.67595.
- American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed., text revision (DSM-5-TR). Washington, DC: American Psychiatric Association Publishing; 2022. Available from: https://www.mredscircleoftrust.com/storage/app/media/DSM%205%20TR.pdf.
- Zeltzer L. Beck depression inventory (BDI, BDI-II). 2008. Available from: https://strokengine.ca/en/assessments/ beckdepression-inventory-bdi-bdi-ii/# References.
- 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.
- Xi YQ, Wang ZQ, Li GJ, Hao ZQ, Nie JH, Li JX, et al. Association of inflammation cytokines with cognitive function in first-episode major depressive disorder. Front Psychiatry. 2025; 15:1473418. doi:10.3389/fpsyt. 2024.1473418.
- Lee STH. Inflammation, depression, and anxiety disorder: a population-based study examining the association between interleukin-6 and the experiencing of depressive and anxiety symptoms. Psychiatry Res. 2020; 285:112809. doi:10.1016/j.psychres.2020.112809.
- Liu H, Wu X, Wang Y, Liu X, Peng D, Wu Y, et al. TNF-α, IL-6 and hsCRP in patients with melancholic, atypical and anxious depression: an antibody array analysis related to somatic symptoms. Gen Psychiatr. 2022; 35(4):e100844. doi:10.1136/gpsych-2022-100844.
- Levi E, Peysachov G, Admon R, Zilcha-Mano S. Cortisol interdependence during psychotherapy in major depressive disorder. Psychoneuroendocrinology. 2024; 163:106983. doi:10.1016/j.psyneuen.2024.106983.
- Patil M, Mukherji P, Wadhai V. Depression detection using blood cortisol levels with machine learning algorithms. In: 2023 Global Conference on Information Technologies and Communications (GCITC). IEEE. 2023:1-5. doi:10.1109/GCITC60406.2023.10425944.
- Genis-Mendoza AD, Dionisio-Garcia DM, Gonzalez-Castro TB, Tovilla-Zarate CA, Juarez-Rojop IE, Lopez-Narvaez ML, et al. Increased levels of cortisol in individuals with suicide attempt and its relation with the number of suicide attempts and depression. Front Psychiatry. 2022; 13:912021. doi:10.3389/fpsyt. 2022.912021.
- Obermanns J, Krawczyk E, Juckel G, Emons B. Analysis of cytokine levels, T regulatory cells and serotonin content in patients with depression. Eur J Neurosci. 2021; 53(10):3476-89. doi:10.1111/ejn.15205.
- Colle R, Masson P, Verstuyft C, Feve B, Werner E, Boursier-Neyret C, et al. Peripheral tryptophan, serotonin, kynurenine, and their metabolites in major depression: a case-control study. Psychiatry Clin Neurosci. 2020; 74(2):112-7. doi:10.1111/pcn.12944.
- Wang Y, Li X, Jing R, Yang W, Wang Y, Wang C, et al. KXS balances the tryptophan metabolism in mild to moderate depressed patients and chronic restraint stress induced depressive rats. Neuropsychiatr Dis Treat. 2022; 18:2485-96. doi:10.2147/NDT.S377982.
- Correia AS, Vale N. Tryptophan metabolism in depression: a narrative review with a focus on serotonin and kynurenine pathways. Int J Mol Sci. 2022; 23(15):8493. doi:10.3390/ijms23158493.
- Koutentaki E, Basta M, Antypa D, Zaganas I, Panagiotakis S, Simos P, et al. IL-6 enhances the negative impact of cortisol on cognition among community-dwelling older people without dementia. Healthcare (Basel). 2023; 11(7):951. doi:10.3390/healthcare11070951.
- Li Y, Yue Y, Chen S, Jiang W, Xu Z, Chen G, et al. Combined serum IL-6, C-reactive protein, and cortisol may distinguish patients with anhedonia in major depressive disorder. Front Mol Neurosci. 2022; 15:935031. doi:10.3389/fnmol.2022.935031.
- Falcicchia C, Tozzi F, Arancio O, Watterson DM, Origlia N. Involvement of p38 MAPK in synaptic function and dysfunction. Int J Mol Sci. 2020; 21(16):5624. doi:10.3390/ijms21165624.
Volume 11 Issue 01
June 2025
