Gender Differences in Cortisol and Cortisol Receptors in Depression: A Narrative Review

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2023 Apr 28

PMID 37108291

Authors

Chuin Hau Teo

Ally Chai Hui Wong

Rooba Nair Sivakumaran

Ishwar Parhar

Tomoko Soga

Affiliations

Soon will be listed here.

Abstract

Stress is known to have a significant impact on mental health. While gender differences can be found in stress response and mental disorders, there are limited studies on the neuronal mechanisms of gender differences in mental health. Here, we discuss gender and cortisol in depression as presented by recent clinical studies, as well as gender differences in the role of glucocorticoid receptors (GRs) and mineralocorticoid receptors (MRs) in stress-associated mental disorders. When examining clinical studies drawn from PubMed/MEDLINE (National Library of Medicine) and EMBASE, salivary cortisol generally showed no gender correlation. However, young males were reported to show heightened cortisol reactivity compared to females of similar age in depression. Pubertal hormones, age, early life stressors, and types of bio-samples for cortisol measurement affected the recorded cortisol levels. The role of GRs and MRs in the HPA axis could be different between males and females during depression, with increased HPA activity and upregulated MR expression in male mice, while the inverse happened in female mice. The functional heterogeneity and imbalance of GRs and MRs in the brain may explain gender differences in mental disorders. This knowledge and understanding will support the development of gender-specific diagnostic markers involving GRs and MRs in depression.

Citing Articles

Depression in adolescence and young adulthood: the difficulty to integrate motivational/emotional systems.

Giacolini T, Alcaro A, Conversi D, Tarsitani L Front Psychol. 2025; 15():1391664.

PMID: 39834756 PMC: 11743547. DOI: 10.3389/fpsyg.2024.1391664.

Genetically predicted smoking and body mass index mediate the relationship between insomnia and myocardial infarction.

Deng L, Gao Y, Wan D, Dong Z, Shao Y, Gao J Front Cardiovasc Med. 2024; 11:1456918.

PMID: 39606186 PMC: 11599222. DOI: 10.3389/fcvm.2024.1456918.

The Interaction of Vasopressin with Hormones of the Hypothalamo-Pituitary-Adrenal Axis: The Significance for Therapeutic Strategies in Cardiovascular and Metabolic Diseases.

Szczepanska-Sadowska E, Czarzasta K, Bogacki-Rychlik W, Kowara M Int J Mol Sci. 2024; 25(13).

PMID: 39000501 PMC: 11242374. DOI: 10.3390/ijms25137394.

Validity of mental and physical stress models.

Hendry E, McCallister B, Elman D, Freeman R, Borsook D, Elman I Neurosci Biobehav Rev. 2024; 158:105566.

PMID: 38307304 PMC: 11082879. DOI: 10.1016/j.neubiorev.2024.105566.

References

Rogerson F, Brennan F, Fuller P . Mineralocorticoid receptor binding, structure and function. Mol Cell Endocrinol. 2004; 217(1-2):203-12. DOI: 10.1016/j.mce.2003.10.021. View

Doane L, Mineka S, Zinbarg R, Craske M, Griffith J, Adam E . Are flatter diurnal cortisol rhythms associated with major depression and anxiety disorders in late adolescence? The role of life stress and daily negative emotion. Dev Psychopathol. 2013; 25(3):629-42. DOI: 10.1017/S0954579413000060. View

Vinkers C, Joels M, Milaneschi Y, Gerritsen L, Kahn R, Penninx B . Mineralocorticoid receptor haplotypes sex-dependently moderate depression susceptibility following childhood maltreatment. Psychoneuroendocrinology. 2015; 54:90-102. DOI: 10.1016/j.psyneuen.2015.01.018. View

Kirschke E, Goswami D, Southworth D, Griffin P, Agard D . Glucocorticoid receptor function regulated by coordinated action of the Hsp90 and Hsp70 chaperone cycles. Cell. 2014; 157(7):1685-97. PMC: 4087167. DOI: 10.1016/j.cell.2014.04.038. View

Boero G, Pisu M, Biggio F, Muredda L, Carta G, Banni S . Impaired glucocorticoid-mediated HPA axis negative feedback induced by juvenile social isolation in male rats. Neuropharmacology. 2018; 133:242-253. DOI: 10.1016/j.neuropharm.2018.01.045. View

Phillips R, Kraeuter A, McDermott B, Lupien S, Sarnyai Z . Human nail cortisol as a retrospective biomarker of chronic stress: A systematic review. Psychoneuroendocrinology. 2020; 123:104903. DOI: 10.1016/j.psyneuen.2020.104903. View

Rao S, Yao Y, Ryan J, Li T, Wang D, Zheng C . Common variants in FKBP5 gene and major depressive disorder (MDD) susceptibility: a comprehensive meta-analysis. Sci Rep. 2016; 6:32687. PMC: 5013409. DOI: 10.1038/srep32687. View

Kumar R, Thompson E . Gene regulation by the glucocorticoid receptor: structure:function relationship. J Steroid Biochem Mol Biol. 2005; 94(5):383-94. DOI: 10.1016/j.jsbmb.2004.12.046. View

Sun Y, Liu Y, Yan S, Hu J, Xu G, Liu J . Longitudinal pattern of early maturation on morning cortisol and depressive symptoms: Sex-specific effects. Psychoneuroendocrinology. 2016; 71:58-63. DOI: 10.1016/j.psyneuen.2016.04.026. View

10.

Buttner M, Jezova D, Greene B, Konrad C, Kircher T, Murck H . Target-based biomarker selection - Mineralocorticoid receptor-related biomarkers and treatment outcome in major depression. J Psychiatr Res. 2015; 66-67:24-37. DOI: 10.1016/j.jpsychires.2015.04.012. View

11.

Tyrka A, Lee J, Graber J, Clement A, Kelly M, DeRose L . Neuroendocrine predictors of emotional and behavioral adjustment in boys: longitudinal follow-up of a community sample. Psychoneuroendocrinology. 2012; 37(12):2042-6. PMC: 3458171. DOI: 10.1016/j.psyneuen.2012.04.004. View

12.

Meewisse M, Reitsma J, Vries G, Gersons B, Olff M . Cortisol and post-traumatic stress disorder in adults: systematic review and meta-analysis. Br J Psychiatry. 2007; 191:387-92. DOI: 10.1192/bjp.bp.106.024877. View

13.

Lu S, Gao W, Huang M, Li L, Xu Y . In search of the HPA axis activity in unipolar depression patients with childhood trauma: Combined cortisol awakening response and dexamethasone suppression test. J Psychiatr Res. 2016; 78:24-30. DOI: 10.1016/j.jpsychires.2016.03.009. View

14.

Daoust A, Kotelnikova Y, Kryski K, Sheikh H, Singh S, Hayden E . Child sex moderates the relationship between cortisol stress reactivity and symptoms over time. Compr Psychiatry. 2018; 87:161-170. DOI: 10.1016/j.comppsych.2018.10.009. View

15.

Xiong J, Lipsitz O, Nasri F, Lui L, Gill H, Phan L . Impact of COVID-19 pandemic on mental health in the general population: A systematic review. J Affect Disord. 2020; 277:55-64. PMC: 7413844. DOI: 10.1016/j.jad.2020.08.001. View

16.

Farrell C, Doolin K, O Leary N, Jairaj C, Roddy D, Tozzi L . DNA methylation differences at the glucocorticoid receptor gene in depression are related to functional alterations in hypothalamic-pituitary-adrenal axis activity and to early life emotional abuse. Psychiatry Res. 2018; 265:341-348. DOI: 10.1016/j.psychres.2018.04.064. View

17.

Hidalgo V, Pulopulos M, Puig-Perez S, Montoliu T, Salvador A . Diurnal cortisol secretion and health-related quality of life in healthy older people. Int J Psychophysiol. 2021; 166:127-133. DOI: 10.1016/j.ijpsycho.2021.05.012. View

18.

Xing G, Russell S, Webster M, Post R . Decreased expression of mineralocorticoid receptor mRNA in the prefrontal cortex in schizophrenia and bipolar disorder. Int J Neuropsychopharmacol. 2004; 7(2):143-53. DOI: 10.1017/S1461145703004000. View

19.

Qing L, Liu L, Zhou L, Zhang F, Gao C, Hu L . Sex-dependent association of mineralocorticoid receptor gene (NR3C2) DNA methylation and schizophrenia. Psychiatry Res. 2020; 292:113318. DOI: 10.1016/j.psychres.2020.113318. View

20.

Powers S, Laurent H, Gunlicks-Stoessel M, Balaban S, Bent E . Depression and anxiety predict sex-specific cortisol responses to interpersonal stress. Psychoneuroendocrinology. 2016; 69:172-9. DOI: 10.1016/j.psyneuen.2016.04.007. View