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

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 (R

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Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare that they have no known conflict of interest that could have appeared to influence the work reported in this paper. Prof. Pariante has received research funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 853966–2, as part of the EU-PEARL project. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA. Prof. Pariante is also funded by a Senior Investigator award from the National Institute for Health Research (NIHR); the Medical Research Council (grants MR/L014815/1, MR/J002739/1 and MR/N029488/1); the European Commission (EARLYCAUSE grant SC1-BHC-01-2019); the NARSAD; the Psychiatry Research Trust; and the Wellcome Trust (SHAPER, Scaling-up Health-Arts Programme to scale up arts interventions, grant 219,425/Z/19/Z). <10 % of his support in the last 10 years derives from commercial collaborations, including consultation and speakers fees from Boehringer Ingelheim, Eli Lilly, Compass, Eleusis, GH Research, Lundbeck, and Värde Partners. Prof. Mondelli is also funded by MQ: Transforming Mental Health (Grant: MQBF/1 and MQBF/4), by the National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London, and the Medical Research Foundation (Grant: MRF-160-0005-ELP-MONDE). Prof. Dazzan has received speaker's fees from Lundbeck and Janssen and is supported by the Medical Research Council (MR/S003444/1). Dr. Lombardo is supported by the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 853966–2, as part of the EU-PEARL project; this Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA. Dr. Nettis has received an honorarium for speaking for Janssen on one occasion.