Disturbed sex hormone milieu in males and females with major depressive disorder and low-grade inflammation

Lombardo, Giulia, Mondelli, Valeria, Worrell, Courtney, Sforzini, Luca, Mariani, Nicole, Nikkheslat, Naghmeh, Nettis, Maria A., Kose, Melisa, Zajkowska, Zuzanna, Cattaneo, Annamaria, Pointon, Linda, Turner, Lorinda, Cowen, Philip J., Drevets, Wayne C., Cavanagh, Jonathan, Harrison, Neil A. ORCID: https://orcid.org/0000-0002-9584-3769, Bullmore, Edward T., Dazzan, Paola and Pariante, Carmine M. 2024. Disturbed sex hormone milieu in males and females with major depressive disorder and low-grade inflammation. Journal of Affective Disorders 356 , pp. 167-176. 10.1016/j.jad.2024.03.018

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Abstract

Sex hormones have biological effects on inflammation, and these might contribute to the sex-specific features of depression. C-reactive protein (CRP) is the most widely used inflammatory biomarker and consistent evidence shows a significant proportion (20–30 %) of patients with major depressive disorder (MDD) have CRP levels above 3 mg/L, a threshold indicating at least low-grade inflammation. Here, we investigate the interplay between sex hormones and CRP in the cross-sectional, observational Biomarkers in Depression Study. We measured serum high-sensitivity (hs-)CRP, in 64 healthy controls and 178 MDD patients, subdivided into those with hs-CRP below 3 mg/L (low-CRP; 53 males, 72 females) and with hs-CRP above 3 mg/L (high-CRP; 19 males, 34 females). We also measured interleukin-6, testosterone, 17-β-estradiol (E2), progesterone, sex-hormone binding globulin (SHBG), follicle-stimulating and luteinising hormones, and calculated testosterone-to-E2 ratio (T/E2), free androgen and estradiol indexes (FAI, FEI), and testosterone secretion index. In males, high-CRP patients had lower testosterone than controls (p = 0.001), and lower testosterone (p = 0.013), T/E2 (p < 0.001), and higher FEI (p = 0.015) than low-CRP patients. In females, high-CRP patients showed lower SHGB levels than controls (p = 0.033) and low-CRP patients (p = 0.034). The differences in testosterone, T/E2 ratio, and FEI levels in males survived the Benjamini-Hochberg FDR correction. In linear regression analyses, testosterone (β = −1.069 p = 0.033) predicted CRP concentrations (R2 = 0.252 p = 0.002) in male patients, and SHBG predicted CRP levels (β = −0.628 p = 0.009, R2 = 0.172 p = 0.003) in female patients. These findings may guide future research investigating interactions between gonadal and immune systems in depression, and the potential of hormonal therapies in MDD with inflammation.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Publisher:	Elsevier
ISSN:	0165-0327
Date of First Compliant Deposit:	23 April 2024
Date of Acceptance:	7 March 2024
Last Modified:	26 Apr 2024 11:30
URI:	https://orca.cardiff.ac.uk/id/eprint/168253

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