Sex steroid hormones in depressive disorders as a basis for new potential treatment strategies
Jazyk angličtina Země Česko Médium print
Typ dokumentu přehledy, časopisecké články
Grantová podpora
R01 MH107886
NIMH NIH HHS - United States
PubMed
36647907
PubMed Central
PMC9906660
DOI
10.33549/physiolres.935001
PII: 935001
Knihovny.cz E-zdroje
- MeSH
- depresivní poruchy * farmakoterapie MeSH
- emoce MeSH
- lidé MeSH
- mladiství MeSH
- mozek metabolismus MeSH
- pohlavní dimorfismus MeSH
- pohlavní steroidní hormony * metabolismus MeSH
- testosteron metabolismus MeSH
- Check Tag
- lidé MeSH
- mladiství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- pohlavní steroidní hormony * MeSH
- testosteron MeSH
The sex steroid hormones (SSHs) such as testosterone, estradiol, progesterone, and their metabolites have important organizational and activational impacts on the brain during critical periods of brain development and in adulthood. A variety of slow and rapid mechanisms mediate both organizational and activational processes via intracellular or membrane receptors for SSHs. Physiological concentrations and distribution of SSHs in the brain result in normal brain development. Nevertheless, dysregulation of hormonal equilibrium may result in several mood disorders, including depressive disorders, later in adolescence or adulthood. Gender differences in cognitive abilities, emotions as well as the 2-3 times higher prevalence of depressive disorders in females, were already described. This implies that SSHs may play a role in the development of depressive disorders. In this review, we discuss preclinical and clinical studies linked to SSHs and development of depressive disorders. Our secondary aim includes a review of up-to-date knowledge about molecular mechanisms in the pathogenesis of depressive disorders. Understanding these molecular mechanisms might lead to significant treatment adjustments for patients with depressive disorders and to an amelioration of clinical outcomes for these patients. Nevertheless, the impact of SSHs on the brain in the context of the development of depressive disorders, progression, and treatment responsiveness is complex in nature, and depends upon several factors in concert such as gender, age, comorbidities, and general health conditions.
Zobrazit více v PubMed
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-5) 5th ed. Washington, DC: 2013. Mood disorder. DOI
Ellenbroek B, Youn J. Gene-Environment Interactions in Psychiatry: Nature, Nurture, Neuroscience. Academic Press; 2016. Affective Disorders; pp. 173–231. DOI
Temin P. Great Depression. In: JONES G, editor. Banking Crises. Palgrave Macmillan; London: 2016. pp. 144–153. DOI
LeMoult J, Gotlib IH. Depression: A cognitive perspective. Clin Psychol Rev. 2019;69:51–66. doi: 10.1016/j.cpr.2018.06.008. PubMed DOI PMC
Lim GY, Tam WW, Lu Y, Ho CS, Zhang MW, Ho RC. Prevalence of depression in the community from 30 countries between 1994 and 2014. Sci Rep. 2018;1:2861. doi: 10.1038/s41598-018-21243-x. PubMed DOI PMC
Murrell SA, Himmelfarb S, Wright K. Prevalence of depression and its correlates in older adults. Am J Epidemiol. 1983;2:173–185. doi: 10.1093/oxfordjournals.aje.a113528. PubMed DOI
Gater R, Tansella M, Korten A, Tiemens BG, Mavreas VG, Olatawura MO. Sex differences in the prevalence and detection of depressive and anxiety disorders in general health care settings: report from the World Health Organization Collaborative Study on Psychological Problems in General Health Care. Arch Gen Psychiatry. 1998;5:405–413. doi: 10.1001/archpsyc.55.5.405. PubMed DOI
Charlson F, van Ommeren M, Flaxman A, Cornett J, Whiteford H, Saxena S. New WHO prevalence estimates of mental disorders in conflict settings: a systematic review and meta-analysis. Lancet. 2019;10194:240–248. doi: 10.1016/S0140-6736(19)30934-1. PubMed DOI PMC
Albert PR. Why is depression more prevalent in women? J Psychiatry Neurosci. 2015;4:219–221. doi: 10.1503/jpn.150205. PubMed DOI PMC
Williams CL. A reevaluation of the concept of separable periods of organizational and activational actions of estrogens in development of brain and behavior. Ann N Y Acad Sci. 1986:282–292. doi: 10.1111/j.1749-6632.1986.tb28019.x. PubMed DOI
Cooke B, Hegstrom CD, Villeneuve LS, Breedlove SM. Sexual differentiation of the vertebrate brain: principles and mechanisms. Front Neuroendocrinol. 1998;4:323–362. doi: 10.1006/frne.1998.0171. PubMed DOI
Schulz KM, Sisk CL. The organizing actions of adolescent gonadal steroid hormones on brain and behavioral development. Neurosci Biobehav Rev. 2016;70:148–158. doi: 10.1016/j.neubiorev.2016.07.036. PubMed DOI PMC
Vigil P, Del Río JP, Carrera B, ArÁnguiz FC, Rioseco H, Cortés ME. Influence of sex steroid hormones on the adolescent brain and behavior: An update. Linacre Q. 2016;3:308–329. doi: 10.1080/00243639.2016.1211863. PubMed DOI PMC
Blankers SA, Galea LAM. Androgens and adult neurogenesis in the hippocampus. Androg Clin Res Ther. 2021;1:203–215. doi: 10.1089/andro.2021.0016. PubMed DOI PMC
Pivina SG, Akulova VK, Ordyan NE. Characteristics of behavior and stress reactivity of the hypophyseal-adrenocortical system in rats with prenatal inhibition of testosterone metabolism. Neurosci Behav Physiol. 2007;1:53–58. doi: 10.1007/s11055-007-0149-6. PubMed DOI
Filová B, Ostatníková D, Celec P, Hodosy J. The effect of testosterone on the formation of brain structures. Cells Tissues Organs. 2013;3:169–177. doi: 10.1159/000345567. PubMed DOI
Kajta M, Wnuk A, Rzemieniec J, Litwa E, Lason W, Zelek-Molik A, Nalepa I, Rogóż Z, Grochowalski A, Wojtowicz AK. Depressive-like effect of prenatal exposure to DDT involves global DNA hypomethylation and impairment of GPER1/ESR1 protein levels but not ESR2 and AHR/ARNT signaling. J Steroid Biochem Mol Biol. 2017;171:94–109. doi: 10.1016/j.jsbmb.2017.03.001. PubMed DOI
Li W, Luo L-Y, Yang X, He Y, Lian B, Qu C-H, Wu Q-Y, Zhang J-G, Xie P. Depressed female cynomolgus monkeys (Macaca fascicularis) display a higher second-to-fourth (2D:4D) digit ratio. Zool Res. 2019;3:219–225. doi: 10.24272/j.issn.2095-8137.2019.022. PubMed DOI PMC
Kessler RC, McGonagle KA, Zhao S, Nelson CB, Hughes M, Eshleman S, Wittchen H-U, Kendler KS. Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States: results from the National Comorbidity Survey. Arch Gen Psychiatry. 1994;1:8–19. doi: 10.1001/archpsyc.1994.03950010008002. PubMed DOI
Mendell AL, MacLusky NJ. Neurosteroid metabolites of gonadal steroid hormones in neuroprotection: implications for sex differences in neurodegenerative disease. Front Mol Neurosci. 2018;11:359. doi: 10.3389/fnmol.2018.00359. PubMed DOI PMC
Solomon MB, Herman JP. Sex differences in psychopathology: of gonads, adrenals and mental illness. Physiol Behav. 2009;2:250–258. doi: 10.1016/j.physbeh.2009.02.033. PubMed DOI PMC
Nolen-Hoeksema S, Larson J, Grayson C. Explaining the gender difference in depressive symptoms. J Pers Soc Psychol. 1999;5:1061–1072. doi: 10.1037/0022-3514.77.5.1061. PubMed DOI
Montgomery JC, Brincat M, Tapp A, Appleby L, Versi E, Fenwick PBC, Studd JWW. Effect of oestrogen and testosterone implants on psychological disorders in the climacteric. Lancet. 1987;8528:297–299. doi: 10.1016/S0140-6736(87)92026-5. PubMed DOI
Fink G, Sumner B, Rosie R, Wilson H, McQueen J. Androgen actions on central serotonin neurotransmission: relevance for mood, mental state and memory. Behav Brain Res. 1999;1:53–68. doi: 10.1016/S0166-4328(99)00082-0. PubMed DOI
Galea LAM, Wide JK, Barr AM. Estradiol alleviates depressive-like symptoms in a novel animal model of post-partum depression. Behav Brain Res. 2001;1:1–9. doi: 10.1016/S0166-4328(01)00170-X. PubMed DOI
Frye C, Walf A, Rhodes M, Harney J. Progesterone enhances motor, anxiolytic, analgesic, and antidepressive behavior of wild-type mice, but not those deficient in type 1 5alpha-reductase. Brain Res. 2004;1004:116–124. doi: 10.1016/j.brainres.2004.01.020. PubMed DOI
Walf AA, Frye CA. Estradiol reduces anxiety- and depression-like behavior of aged female mice. Physiol Behav. 2010;2:169–174. doi: 10.1016/j.physbeh.2009.09.017. PubMed DOI PMC
Miller KK, Wexler TL, Zha AM, Lawson EA, Meenaghan EM, Misra M, Binstock AB, Herzog DB, Klibanski A. Androgen deficiency: association with increased anxiety and depression symptom severity in anorexia nervosa. J Clin Psych. 2007;6:959–965. doi: 10.4088/JCP.v68n0621. PubMed DOI
Chaudhari AP, Mazumdar K, Mehta PD. Anxiety, depression, and quality of life in women with polycystic ovarian syndrome. Indian J Psychol Med. 2018;3:239–246. doi: 10.4103/IJPSYM.IJPSYM_561_17. PubMed DOI PMC
Gordon JL, Peltier A, Grummisch JA, Sykes Tottenham L. Estradiol fluctuation, sensitivity to stress, and depressive symptoms in the menopause transition: a pilot study. Front Psychol. 2019;10:1319. doi: 10.3389/fpsyg.2019.01319. PubMed DOI PMC
Goldstein JM, Seidman LJ, Horton NJ, Makris N, Kennedy DN, Caviness VS, Jr, Faraone SV, Tsuang MT. Normal sexual dimorphism of the adult human brain assessed by in vivo magnetic resonance imaging. Cereb Cortex. 2001;6:490–497. doi: 10.1093/cercor/11.6.490. PubMed DOI
Goldman-Rakic PS, Cools AR, Srivastava K, Roberts AC, Robbins TW, Weiskrantz L. The prefrontal landscape: implications of functional architecture for understanding human mentation and the central executive. Philos Trans R Soc Lond B Biol Sci. 1996;1346:1445–1453. doi: 10.1098/rstb.1996.0129. PubMed DOI
Teffer K, Semendeferi K. Human prefrontal cortex: Evolution, development, and pathology. In: HOFMAN MA, FALK D, editors. Progress in Brain Research. Elsevier; 2012. pp. 191–218. PubMed DOI
Miller EK, Cohen JD. An integrative theory of prefrontal cortex function. Annu Rev Neurosci. 2001;1:167–202. doi: 10.1146/annurev.neuro.24.1.167. PubMed DOI
Funahashi S, Bruce CJ, Goldman-Rakic PS. Dorsolateral prefrontal lesions and oculomotor delayed-response performance: evidence for mnemonic “scotomas”. J Neurosci. 1993;4:1479–1497. doi: 10.1523/JNEUROSCI.13-04-01479.1993. PubMed DOI PMC
Gabrieli JDE, Poldrack RA, Desmond JE. The role of left prefrontal cortex in language and memory. Proc Natl Acad Sci U S A. 1998;3:906. doi: 10.1073/pnas.95.3.906. PubMed DOI PMC
Guadagno A, Belliveau C, Mechawar N, Walker C-D. Effects of early life stress on the developing basolateral amygdala-prefrontal cortex circuit: the emerging role of local inhibition and perineuronal nets. Front Hum Neurosci. 2021;15:669120. doi: 10.3389/fnhum.2021.669120. PubMed DOI PMC
Feldman S, Conforti N, Weidenfeld J. Limbic pathways and hypothalamic neurotransmitters mediating adrenocortical responses to neural stimuli. Neurosci Biobehav Rev. 1995;2:235–240. doi: 10.1016/0149-7634(94)00062-6. PubMed DOI
Öhman A. The role of the amygdala in human fear: Automatic detection of threat. Psychoneuroendocrinology. 2005;10:953–958. doi: 10.1016/j.psyneuen.2005.03.019. PubMed DOI
Baxter MG, Croxson PL. Facing the role of the amygdala in emotional information processing. Proc Natl Acad Sci U S A. 2012;52:21180. doi: 10.1073/pnas.1219167110. PubMed DOI PMC
Höfer P, Lanzenberger R, Kasper S. Testosterone in the brain: Neuroimaging findings and the potential role for neuropsychopharmacology. Eur Neuropsychopharmacol. 2013;2:79–88. doi: 10.1016/j.euroneuro.2012.04.013. PubMed DOI
Papadimitriou A, Priftis KN. Regulation of the hypothalamic-pituitary-adrenal axis. Neuroimmunomodulation. 2009;5:265–271. doi: 10.1159/000216184. PubMed DOI
Sheline YI, Mittler BL, Mintun MA. The hippocampus and depression. Eur Psychiatry. 2002;S3:300s–305s. doi: 10.1016/S0924-9338(02)00655-7. PubMed DOI
Campbell M, Jialal I. StatPearls. Treasure Island (FL): StatPearls Publishing; 2022. Physiology, Endocrine Hormones. PubMed
Anand KS, Dhikav V. Hippocampus in health and disease: An overview. Ann Ind Acad Neurol. 2012;4:239–246. doi: 10.4103/0972-2327.104323. PubMed DOI PMC
Stevens JS, Hamann S. Sex differences in brain activation to emotional stimuli: A meta-analysis of neuroimaging studies. Neuropsychologia. 2012;7:1578–1593. doi: 10.1016/j.neuropsychologia.2012.03.011. PubMed DOI
Varidaki A, Mohammad H, Coffey ET. Molecular mechanisms of depression. In: FRODL T, editor. Systems Neuroscience in Depression. Academic Press; 2016. pp. 143–178. DOI
Hare BD, Duman RS. Prefrontal cortex circuits in depression and anxiety: contribution of discrete neuronal populations and target regions. Mol Psychiatry. 2020;11:2742–2758. doi: 10.1038/s41380-020-0685-9. PubMed DOI PMC
Guerra-Araiza C, Coyoy-Salgado A, Camacho-Arroyo I. Sex differences in the regulation of progesterone receptor isoforms expression in the rat brain. Brain Res Bull. 2002;2:105–109. doi: 10.1016/S0361-9230(02)00845-6. PubMed DOI
Foster TC. Role of estrogen receptor alpha and beta expression and signaling on cognitive function during aging. Hippocampus. 2012;4:656–669. doi: 10.1002/hipo.20935. PubMed DOI PMC
Berg AH, Rice CD, Rahman MS, Dong J, Thomas P. Identification and characterization of membrane androgen receptors in the ZIP9 zinc transporter subfamily: I. Discovery in female atlantic croaker and evidence ZIP9 mediates testosterone-induced apoptosis of ovarian follicle cells. Endocrinology. 2014;11:4237–4249. doi: 10.1210/en.2014-1198. PubMed DOI PMC
Almey A, Milner TA, Brake WG. Estrogen receptors in the central nervous system and their implication for dopamine-dependent cognition in females. Horm Behav. 2015:125–138. doi: 10.1016/j.yhbeh.2015.06.010. PubMed DOI PMC
Pérez SE, Chen EY, Mufson EJ. Distribution of estrogen receptor alpha and beta immunoreactive profiles in the postnatal rat brain. Dev Brain Res. 2003;1:117–139. doi: 10.1016/S0165-3806(03)00223-2. PubMed DOI
Gorelick DA, Watson W, Halpern ME. Androgen receptor gene expression in the developing and adult zebrafish brain. Dev Dyn. 2008;10:2987–2995. doi: 10.1002/dvdy.21700. PubMed DOI
Belovicova K, Bogi E, Csatlosova K, Dubovicky M. Animal tests for anxiety-like and depression-like behavior in rats. Interdiscip Toxicol. 2017;1:40–43. doi: 10.1515/intox-2017-0006. PubMed DOI PMC
Carrier N, Kabbaj M. Testosterone and imipramine have antidepressant effects in socially isolated male but not female rats. Horm Behav. 2012;5:678–685. doi: 10.1016/j.yhbeh.2012.03.001. PubMed DOI PMC
Zhang JM, Tonelli L, Regenold WT, McCarthy MM. Effects of neonatal flutamide treatment on hippocampal neurogenesis and synaptogenesis correlate with depression-like behaviors in preadolescent male rats. Neuroscience. 2010;1:544–554. doi: 10.1016/j.neuroscience.2010.03.029. PubMed DOI PMC
Manning J, Kilduff L, Cook C, Crewther B, Fink B. Digit ratio (2D: 4D): a biomarker for prenatal sex steroids and adult sex steroids in challenge situations. Front Endocrinol (Lausanne) 2014;5:9. doi: 10.3389/fendo.2014.00009. PubMed DOI PMC
Ventura T, Gomes MC, Pita A, Neto MT, Taylor A. Digit ratio (2D:4D) in newborns: Influences of prenatal testosterone and maternal environment. Early Hum Dev. 2013;2:107–112. doi: 10.1016/j.earlhumdev.2012.08.009. PubMed DOI
McHenry J, Carrier N, Hull E, Kabbaj M. Sex differences in anxiety and depression: role of testosterone. Front Neuroendocrinol. 2014;1:42–57. doi: 10.1016/j.yfrne.2013.09.001. PubMed DOI PMC
Black SR, Goldstein BL, Klein DN. Parental depression moderates the relationships of cortisol and testosterone with children’s symptoms. J Affect Disord. 2019;251:42–51. doi: 10.1016/j.jad.2019.01.047. PubMed DOI PMC
Su Q-R, Su L-Y, Su H-R, Chen Q, Ren G-Y, Yin YOU, Shen S-Q, Yu A-Y, Xia G-Y. Polymorphisms of androgen receptor gene in childhood and adolescent males with first-onset major depressive disorder and association with related symptomatology. Int J Neurosci. 2007;7:903–917. doi: 10.1080/00207450600910689. PubMed DOI
Sankar JS, Hampson E. Testosterone levels and androgen receptor gene polymorphism predict specific symptoms of depression in young men. Gend Med. 2012;4:232–243. doi: 10.1016/j.genm.2012.05.001. PubMed DOI
Chamberlain NL, Driver ED, Miesfeld RL. The length and location of CAG trinucleotide repeats in the androgen receptor N-terminal domain affect transactivation function. Nucleic Acids Res. 1994;15:3181–3186. doi: 10.1093/nar/22.15.3181. PubMed DOI PMC
Tut TG, Ghadessy FJ, Trifiro M, Pinsky L, Yong E. Long polyglutamine tracts in the androgen receptor are associated with reduced trans-activation, impaired sperm production, and male infertility. J Clin Endocrinol Metab. 1997;11:3777–3782. doi: 10.1210/jc.82.11.3777. PubMed DOI
Möhlig M, Arafat AM, Osterhoff MA, Isken F, Weickert MO, Spranger J, Pfeiffer AF, Schöfl C. Androgen receptor CAG repeat length polymorphism modifies the impact of testosterone on insulin sensitivity in men. Europ J Endocrinol. 2011;6:1013. doi: 10.1530/EJE-10-1022. PubMed DOI
Tsai S-J, Wang Y-C, Hong C-J, Chiu H-J. Association study of oestrogen receptor α gene polymorphism and suicidal behaviours in major depressive disorder. Psychiatr Genet. 2003;1:19–22. doi: 10.1097/00041444-200303000-00003. PubMed DOI
Kravitz HM, Janssen I, Lotrich FE, Kado DM, Bromberger JT. Sex steroid hormone gene polymorphisms and depressive symptoms in women at midlife. Am J Med. 2006;119(9 Suppl 1):S87–S93. doi: 10.1016/j.amjmed.2006.07.010. PubMed DOI
Seidman SN, Araujo AB, Roose SP, McKinlay JB. Testosterone level, androgen receptor polymorphism, and depressive symptoms in middle-aged men. Biol Psychiatry. 2001;5:371–376. doi: 10.1016/S0006-3223(01)01148-9. PubMed DOI
Chhibber A, Woody SK, Karim Rumi MA, Soares MJ, Zhao L. Estrogen receptor β deficiency impairs BDNF-5-HT(2A) signaling in the hippocampus of female brain: A possible mechanism for menopausal depression. Psychoneuroendocrinology. 2017;82:107–116. doi: 10.1016/j.psyneuen.2017.05.016. PubMed DOI PMC
Schüle C, Eser D, Baghai TC, Nothdurfter C, Kessler JS, Rupprecht R. Neuroactive steroids in affective disorders: target for novel antidepressant or anxiolytic drugs? Neuroscience. 2011;191:55–77. doi: 10.1016/j.neuroscience.2011.03.025. PubMed DOI
Wang J, Li H-Y, Shen S-Y, Zhang J-R, Liang L-F, Huang H-J, Li B, Wu G-C, Zhang Y-Q, Yu J. The antidepressant and anxiolytic effect of GPER on translocator protein (TSPO) via protein kinase a (PKA) signaling in menopausal female rats. J Steroid Biochem Mol Biol. 2021;207:105807. doi: 10.1016/j.jsbmb.2020.105807. PubMed DOI
Findikli E, Kurutas EB, Camkurt MA, Karaaslan MF, Izci F, Fındıklı HA, Kardaş S, Dag B, Altun H. Increased serum G protein-coupled estrogen receptor 1 levels and its diagnostic value in drug naïve patients with major depressive disorder. Clin Psychopharmacol Neurosci. 2017;4:337–342. doi: 10.9758/cpn.2017.15.4.337. PubMed DOI PMC
Hung Y-Y, Huang Y-L, Chang C, Kang H-Y. Deficiency in androgen receptor aggravates the depressive-like behaviors in chronic mild stress model of depression. Cells. 2019;9:1021. doi: 10.3390/cells8091021. PubMed DOI PMC
Furuta M, Numakawa T, Chiba S, Ninomiya M, Kajiyama Y, Adachi N, Akema T, Kunugi H. Estrogen, predominantly via estrogen receptor α, attenuates postpartum-induced anxiety- and depression-like behaviors in female rats. Endocrinology. 2013;10:3807–3816. doi: 10.1210/en.2012-2136. PubMed DOI
Rocha BA, Fleischer R, Schaeffer JM, Rohrer SP, Hickey GJ. 17β-Estradiol-induced antidepressant-like effect in the Forced Swim Test is absent in estrogen receptor-β knockout (BERKO) mice. Psychopharmacology. 2005;3:637–643. doi: 10.1007/s00213-004-2078-1. PubMed DOI
Bastos CP, Pereira LM, Ferreira-Vieira TH, Drumond LE, Massensini AR, Moraes MF, Pereira GS. Object recognition memory deficit and depressive-like behavior caused by chronic ovariectomy can be transitorialy recovered by the acute activation of hippocampal estrogen receptors. Psychoneuroendocrinology. 2015;57:14–25. doi: 10.1016/j.psyneuen.2015.03.020. PubMed DOI
Walf AA, Frye CA. Administration of estrogen receptor beta-specific selective estrogen receptor modulators to the hippocampus decrease anxiety and depressive behavior of ovariectomized rats. Pharmacol Biochem Behav. 2007;2:407–414. doi: 10.1016/j.pbb.2006.07.003. PubMed DOI
Walf AA, Frye CA. A review and update of mechanisms of estrogen in the hippocampus and amygdala for anxiety and depression behavior. Neuropsychopharmacology. 2006;6:1097–1111. doi: 10.1038/sj.npp.1301067. PubMed DOI PMC
Xu Y, Sheng H, Bao Q, Wang Y, Lu J, Ni X. NLRP3 inflammasome activation mediates estrogen deficiency-induced depression- and anxiety-like behavior and hippocampal inflammation in mice. Brain Behav Immun. 2016:175–186. doi: 10.1016/j.bbi.2016.02.022. PubMed DOI
Wang J, Yu R, Han Q-Q, Huang H-J, Wang Y-L, Li H-Y, Wang H-M, Chen X-R, Ma S-L, Yu J. G-1 exhibit antidepressant effect, increase of hippocampal ERs expression and improve hippocampal redox status in aged female rats. Behav Brain Res. 2019;359:845–852. doi: 10.1016/j.bbr.2018.07.017. PubMed DOI
Bopassa JC, Eghbali M, Toro L, Stefani E. A novel estrogen receptor GPER inhibits mitochondria permeability transition pore opening and protects the heart against ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol. 2010;1:H16–H23. doi: 10.1152/ajpheart.00588.2009. PubMed DOI PMC
Jia C, Brown RW, Malone HM, Burgess KC, Gill WD, Keasey MP, Hagg T. Ciliary neurotrophic factor is a key sex-specific regulator of depressive-like behavior in mice. Psychoneuroendocrinology. 2019;100:96–105. doi: 10.1016/j.psyneuen.2018.09.038. PubMed DOI PMC
Hellgren C, Åkerud H, Skalkidou A, Bäckström T, Sundström-Poromaa I. Low serum allopregnanolone is associated with symptoms of depression in late pregnancy. Neuropsychobiology. 2014;3:147–153. doi: 10.1159/000358838. PubMed DOI
Almeida FB, Nin MS, Barros HMT. The role of allopregnanolone in depressive-like behaviors: Focus on neurotrophic proteins. Neurobiol Stres. 2020;12:100218. doi: 10.1016/j.ynstr.2020.100218. PubMed DOI PMC
Schüle C, Nothdurfter C, Rupprecht R. The role of allopregnanolone in depression and anxiety. Prog Neurobiol. 2014:79–87. doi: 10.1016/j.pneurobio.2013.09.003. PubMed DOI
Frye CA, Walf AA. Changes in progesterone metabolites in the hippocampus can modulate open field and forced swim test behavior of proestrous rats. Horm Behav. 2002;3:306–315. doi: 10.1006/hbeh.2002.1763. PubMed DOI
Shirayama Y, Fujita Y, Oda Y, Iwata M, Muneoka K, Hashimoto K. Allopregnanolone induces antidepressant-like effects through BDNF-TrkB signaling independent from AMPA receptor activation in a rat learned helplessness model of depression. Behav Brain Res. 2020;390:112670. doi: 10.1016/j.bbr.2020.112670. PubMed DOI
Chen S, Gao L, Li X, Ye Y. Allopregnanolone in mood disorders: Mechanism and therapeutic development. Pharmacol Res. 2021;169:105682. doi: 10.1016/j.phrs.2021.105682. PubMed DOI
Bao A-M, Swaab DF. The human hypothalamus in mood disorders: the HPA axis in the center. IBRO Rep. 2019;6:45–53. doi: 10.1016/j.ibror.2018.11.008. PubMed DOI PMC
Vamvakopoulos NC, Chrousos GP. Evidence of direct estrogenic regulation of human corticotropin-releasing hormone gene expression. Potential implications for the sexual dimophism of the stress response and immune/inflammatory reaction. J Clin Invest. 1993;4:1896–1902. doi: 10.1172/JCI116782. PubMed DOI PMC
Bao A, Fischer D, Wu Y, Hol E, Balesar R, Unmehopa U, Zhou J, Swaab D. A direct androgenic involvement in the expression of human corticotropin-releasing hormone. Mol Psychiatry. 2006;6:567–576. doi: 10.1038/sj.mp.4001800. PubMed DOI
Bibel M, Barde Y. Neurotrophins: key regulators of cell fate and cell shape in the vertebrate nervous system. Genes Dev. 2000;14:2919–2937. doi: 10.1101/gad.841400. PubMed DOI
Berton O, McClung CA, DiLeone RJ, Krishnan V, Renthal W, Russo SJ, Graham D, Tsankova NM, Bolanos CA, Rios M, Monteggia LM, Self DW, Nestler EJ. Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress. Science. 2006;5762:864–868. doi: 10.1126/science.1120972. PubMed DOI
Numakawa T, Odaka H, Adachi N. Actions of brain-derived neurotrophin factor in the neurogenesis and neuronal function, and its involvement in the pathophysiology of brain diseases. Int J Mol Sci. 2018;11:3650. doi: 10.3390/ijms19113650. PubMed DOI PMC
Verhagen M, van der Meij A, van Deurzen PAM, Janzing JGE, Arias-Vásquez A, Buitelaar JK, Franke B. Meta-analysis of the BDNF Val66Met polymorphism in major depressive disorder: effects of gender and ethnicity. Mol Psychiatry. 2010;3:260–271. doi: 10.1038/mp.2008.109. PubMed DOI
von Richthofen S, Lang UE, Hellweg R. Effects of different kinds of acute stress on nerve growth factor content in rat brain. Brain Res. 2003;2:207–213. doi: 10.1016/S0006-8993(03)03338-9. PubMed DOI
Lange I, Meyer H. The gastrointestinal tract as target of steroid hormone action: quantification of steroid receptor mRNA expression (AR, ERalpha, ERbeta and PR) in 10 bovine gastrointestinal tract compartments by kinetic RT-PCR. J Steroid Biochem Mol Biol. 2003;84:159–166. doi: 10.1016/S0960-0760(03)00025-6. PubMed DOI
Campbell S, MacQueen G. The role of the hippocampus in the pathophysiology of major depression. J Psychiatry Neurosci. 2004;6:417–426. PubMed PMC
Sen S, Duman R, Sanacora G. Serum brain-derived neurotrophic factor, depression, and antidepressant medications: meta-analyses and implications. Biol Psychiatry. 2008;6:527–532. doi: 10.1016/j.biopsych.2008.05.005. PubMed DOI PMC
Nomoto H, Baba H, Satomura E, Maeshima H, Takebayashi N, Namekawa Y, Suzuki T, Arai H. Serum brain-derived neurotrophic factor levels and personality traits in patients with major depression. BMC Psychiatry. 2015;1:33. doi: 10.1186/s12888-015-0413-1. PubMed DOI PMC
Emon MPZ, Das R, Nishuty NL, Shalahuddin Qusar MMA, Bhuiyan MA, Islam MR. Reduced serum BDNF levels are associated with the increased risk for developing MDD: a case-control study with or without antidepressant therapy. BMC Res Notes. 2020;1:83. doi: 10.1186/s13104-020-04952-3. PubMed DOI PMC
Mahmoud R, Wainwright SR, Galea LAM. Sex hormones and adult hippocampal neurogenesis: Regulation, implications, and potential mechanisms. Front Neuroendocrinol. 2016;41:129–152. doi: 10.1016/j.yfrne.2016.03.002. PubMed DOI
Ihara K, Yoshida H, Jones PB, Hashizume M, Suzuki Y, Ishijima H, Kim HK, Suzuki T, Hachisu M. Serum BDNF levels before and after the development of mood disorders: a case-control study in a population cohort. Transl Psychiatr. 2016;4:e782–e782. doi: 10.1038/tp.2016.47. PubMed DOI PMC
Pedrotti Moreira F, Cardoso TC, Mondin TC, Wiener CD, de Mattos Souza LD, Oses JP, Jansen K, da Silva RA. Serum level of nerve growth factor is a potential biomarker of conversion to bipolar disorder in women with major depressive disorder. Psychiatr Clin Neurosci. 2019;9:590–593. doi: 10.1111/pcn.12896. PubMed DOI
Rasika S, Alvarez-Buylla A, Nottebohm F. BDNF Mediates the effects of testosterone on the survival of New Neurons in an adult brain. Neuron. 1999;1:53–62. doi: 10.1016/S0896-6273(00)80678-9. PubMed DOI
Espallergues J, Mamiya T, Vallée M, Koseki T, Nabeshima T, Temsamani J, Laruelle C, Maurice T. The antidepressant-like effects of the 3β-hydroxysteroid dehydrogenase inhibitor trilostane in mice is related to changes in neuroactive steroid and monoamine levels. Neuropharmacology. 2012;1:492–502. doi: 10.1016/j.neuropharm.2011.09.005. PubMed DOI
Su Q, Cheng Y, Jin K, Cheng J, Lin Y, Lin Z, Wang L, Shao B. Estrogen therapy increases BDNF expression and improves post-stroke depression in ovariectomy-treated rats. Exp Ther Med. 2016;3:1843–1848. doi: 10.3892/etm.2016.3531. PubMed DOI PMC
Meltzer-Brody S, Colquhoun H, Riesenberg R, Epperson CN, Deligiannidis KM, Rubinow DR, Li H, Sankoh AJ, Clemson C, Schacterle A. Brexanolone injection in post-partum depression: two multicentre, double-blind, randomised, placebo-controlled, phase 3 trials. The Lancet. 2018;10152:1058–1070. doi: 10.1016/S0140-6736(18)31551-4. PubMed DOI
Powell JG, Garland S, Preston K, Piszczatoski C. Brexanolone (Zulresso): Finally, an FDA-approved treatment for postpartum depression. Ann Pharmacother. 2019;2:157–163. doi: 10.1177/1060028019873320. PubMed DOI
Wirth M. Beyond the HPA axis: progesterone-derived neuroactive steroids in human stress and emotion. Front Endocrinol (Lausanne) 2011;2:19. doi: 10.3389/fendo.2011.00019. PubMed DOI PMC
Agis-Balboa RC, Guidotti A, Pinna G. 5α-reductase type I expression is downregulated in the prefrontal cortex/Brodmann’s area 9 (BA9) of depressed patients. Psychopharmacology. 2014;17:3569–3580. doi: 10.1007/s00213-014-3567-5. PubMed DOI PMC
Rasmusson AM, Pinna G, Paliwal P, Weisman D, Gottschalk C, Charney D, Krystal J, Guidotti A. Decreased cerebrospinal fluid allopregnanolone levels in women with posttraumatic stress disorder. Biol Psychiatry. 2006;7:704–713. doi: 10.1016/j.biopsych.2006.03.026. PubMed DOI
Romeo E, Ströhle A, Spalletta G, Michele Fd, Hermann B, Holsboer F, Pasini A, Rupprecht R. Effects of antidepressant treatment on neuroactive steroids in major depression. Am J Psychiatry. 1998;7:910–913. doi: 10.1176/ajp.155.7.910. PubMed DOI
Pinna G, Costa E, Guidotti A. Fluoxetine and norfluoxetine stereospecifically and selectively increase brain neurosteroid content at doses that are inactive on 5-HT reuptake. Psychopharmacology. 2006;3:362–372. doi: 10.1007/s00213-005-0213-2. PubMed DOI
Uzunova V, Sheline Y, Davis J, Rasmusson A, Uzunov D, Costa E, Guidotti A. Increase in the cerebrospinal fluid content of neurosteroids in patients with unipolar major depression who are receiving fluoxetine or fluvoxamine. Proc Natl Acad Sci U S A. 1998;6:3239–3244. doi: 10.1073/pnas.95.6.3239. PubMed DOI PMC
Romeo E, Pompili E, Michele Fd, Pace M, Rupprecht R, Bernardi G, Pasinib A. Effects of fluoxetine, indomethacine and placebo on 3α, 5α tetrahydroprogesterone (THP) plasma levels in uncomplicated alcohol withdrawal. World J Biol Psychiatry. 2000;2:101–104. doi: 10.3109/15622970009150572. PubMed DOI
Schüle C, Romeo E, Uzunov D, Eser D, Di Michele F, Baghai T, Pasini A, Schwarz M, Kempter H, Rupprecht R. Influence of mirtazapine on plasma concentrations of neuroactive steroids in major depression and on 3α-hydroxysteroid dehydrogenase activity. Mol Psychiatry. 2006;3:261–272. doi: 10.1038/sj.mp.4001782. PubMed DOI
Ugale RR, Hirani K, Morelli M, Chopde CT. Role of neuroactive steroid allopregnanolone in antipsychotic-like action of olanzapine in rodents. Neuropsychopharmacology. 2004;9:1597–1609. doi: 10.1038/sj.npp.1300460. PubMed DOI
Prasad A. Efficacy of carbamazepine as an antidepressant in chronic resistant depressives. J Indian Med Assoc. 1985;7:235–237. PubMed
Kobayashi T, Kishimoto A, Inagaki T. Treatment of periodic depression with carbamazepine. Acta Psychiatr Scand. 1988;3:364–367. doi: 10.1111/j.1600-0447.1988.tb05137.x. PubMed DOI
Kanes S, Colquhoun H, Gunduz-Bruce H, Raines S, Arnold R, Schacterle A, Doherty J, Epperson CN, Deligiannidis KM, Riesenberg R. Brexanolone (SAGE-547 injection) in post-partum depression: a randomised controlled trial. Lancet. 2017;10093:480–489. doi: 10.1016/S0140-6736(17)31264-3. PubMed DOI
Kanes SJ, Colquhoun H, Doherty J, Raines S, Hoffmann E, Rubinow DR, Meltzer-Brody S. Open-label, proof-of-concept study of brexanolone in the treatment of severe postpartum depression. Hum Psychopharmacol Clin Exp. 2017;2:e2576. doi: 10.1002/hup.2576. PubMed DOI PMC
Meltzer-Brody S, Kanes SJ. Allopregnanolone in postpartum depression: Role in pathophysiology and treatment. Neurobiol Stres. 2020;12:100212. doi: 10.1016/j.ynstr.2020.100212. PubMed DOI PMC
Chen CV, Jordan CL, Breedlove SM. Testosterone works through androgen receptors to modulate neuronal response to anxiogenic stimuli. Neurosci Lett. 2021;753:135852. doi: 10.1016/j.neulet.2021.135852. PubMed DOI
Sternbach H. Age-associated testosterone decline in men: clinical issues for psychiatry. Am J Psychiatry. 1998;10:1310–1318. doi: 10.1176/ajp.155.10.1310. PubMed DOI
Khera M, Bhattacharya R, Blick Md G, Kushner H, Nguyen D, Miner M. The effect of testosterone supplementation on depression symptoms in hypogonadal men from the Testim Registry in the US (TRiUS) Aging Male. 2011;15:14–21. doi: 10.3109/13685538.2011.606513. PubMed DOI
Zarrouf FA, Artz S, Griffith J, Sirbu C, Kommor M. Testosterone and depression: systematic review and meta-analysis. J Psychiatr Pract. 2009;4:289–305. doi: 10.1097/01.pra.0000358315.88931.fc. PubMed DOI
Amiaz R, Seidman SN. Testosterone and depression in men. Curr Opin Endocrinol Diabetes Obes. 2008;3:278–283. doi: 10.1097/MED.0b013e3282fc27eb. PubMed DOI
Shores MM. Men’s Health and Psychiatry. In: ALUKAL JP, LAMM S, WALSH TJ, editors. Design and Implementation of the Modern Men’s Health Center. Springer Nature; Switzerland: 2021. pp. 231–248.
Vartolomei MD, Kimura S, Vartolomei L, Shariat SF. Systematic review of the impact of testosterone replacement therapy on depression in patients with late-onset testosterone deficiency. Eur Urol Focus. 2020;1:170–177. doi: 10.1016/j.euf.2018.07.006. PubMed DOI