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Sex hormone fluctuation and increased female risk for depression and anxiety disorders: From clinical evidence to molecular mechanisms
Open accessAbstract
Women are at twice the risk for anxiety and depression disorders as men are, although the underlying biological factors and mechanisms are largely unknown. In this review, we address this sex disparity at both the etiological and mechanistic level. We dissect the role of fluctuating sex hormones as a critical biological factor contributing to the increased depression and anxiety risk in women. We provide parallel evidence in humans and rodents that brain structure and function vary with naturally-cycling ovarian hormones. This female-unique brain plasticity and associated vulnerability are primarily driven by estrogen level changes. For the first time, we provide a sex hormone-driven molecular mechanism, namely chromatin organizational changes, that regulates neuronal gene expression and brain plasticity but may also prime the (epi)genome for psychopathology. Finally, we map out future directions including experimental and clinical studies that will facilitate novel sex- and gender-informed approaches to treat depression and anxiety disorders.
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Egan, M. F., Kojima, M., Callicott, J. H., Goldberg, T. E., Kolachana, B. S., Bertolino, A., Zaitsev, E., Gold, B., Goldman, D., Dean, M., et al. (2003) · Cell · doi:10.1016/s0092-8674(03)00035-7 · Cited by 3,888
Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus
van Praag, H., Kempermann, G., & Gage, F. H. (1999) · Nature Neuroscience · doi:10.1038/6368 · Cited by 3,880
Gene regulation by steroid hormones
Beato, M. (1989) · Cell · doi:10.1016/0092-8674(89)90237-7 · Cited by 3,383
Are the Dorsal and Ventral Hippocampus Functionally Distinct Structures?
Fanselow, M. S., & Dong, H.-W. (2010) · Neuron · doi:10.1016/j.neuron.2009.11.031 · Cited by 3,358
Rates and risk of postpartum depression – a meta-analysis
O'hara, M. W., & Swain, A. M. (1996) · International Review of Psychiatry · doi:10.3109/09540269609037816 · Cited by 3,116
Howard, D. M., Adams, M. J., Clarke, T.-K., Hafferty, J. D., Gibson, J., Shirali, M., Coleman, J. R. I., Hagenaars, S. P., Ward, J., Wigmore, E. M., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-018-0326-7 · Cited by 2,565
Otte, C., Gold, S. M., Penninx, B. W., Pariante, C. M., Etkin, A., Fava, M., Mohr, D. C., & Schatzberg, A. F. (2016) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2016.65 · Cited by 2,269 · cited 1×
“…disorders, of which major depressive disorder (MDD) is the most common, are characterized by depressed mood, diminished interests or an inability to feel pleasure, impaired cognitive function, and vegetative symptoms such as loss of energy and disturbed sleep or appetite (Otte et al., 2016).”
Epidemiology of anxiety disorders in the 21st century
Bandelow, B., & Michaelis, S. (2015) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2015.17.3/bbandelow · Cited by 2,079
Mindfulness practice leads to increases in regional brain gray matter density
Hölzel, B. K., Carmody, J., Vangel, M., Congleton, C., Yerramsetti, S. M., Gard, T., & Lazar, S. W. (2011) · Psychiatry Research: Neuroimaging · doi:10.1016/j.pscychresns.2010.08.006 · Cited by 1,914
Why is depression more common among women than among men?
Kuehner, C. (2017) · The Lancet Psychiatry · doi:10.1016/s2215-0366(16)30263-2 · Cited by 1,752
Epidemiology of Adult DSM-5 Major Depressive Disorder and Its Specifiers in the United States
Hasin, D. S., Sarvet, A. L., Meyers, J. L., Saha, T. D., Ruan, W. J., Stohl, M., & Grant, B. F. (2018) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2017.4602 · Cited by 1,737 · cited 1×
“Depression and anxiety disorders are highly prevalent, debilitating, and often co-morbid mental disorders, with reported life-time prevalence rates of 20.6% (Hasin et al., 2018) and up to 33.7% (Bandelow and Michaelis, 2015), respectively.”
InfluentialSex differences in anxiety and depression clinical perspectives
Altemus, M., Sarvaiya, N., & Neill Epperson, C. (2014) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2014.05.004 · Cited by 1,413 · cited 5×
“…are all likely contributors (Li and Graham, 2017), a strong body of evidence implicates sex hormone fluctuation in women as the major biological factor driving sex differences in anxiety and depression risk (Altemus et al., 2014; Deecher et al., 2008; Soares and Zitek, 2008; Steiner et al., 2003).”
InfluentialOrganizational principles of 3D genome architecture
Rowley, M. J., & Corces, V. G. (2018) · Nature Reviews Genetics · doi:10.1038/s41576-018-0060-8 · Cited by 1,171
Postmenopausal Hormone Replacement Therapy: Scientific Review
Nelson, H. D., Humphrey, L. L., Nygren, P., Teutsch, S. M., & Allan, J. D. (2002) · JAMA · doi:10.1001/jama.288.7.872 · Cited by 990
Differential Control of Learning and Anxiety along the Dorsoventral Axis of the Dentate Gyrus
Kheirbek, M. A., Drew, L. J., Burghardt, N. S., Costantini, D. O., Tannenholz, L., Ahmari, S. E., Zeng, H., Fenton, A. A., & Hen, R. (2013) · Neuron · doi:10.1016/j.neuron.2012.12.038 · Cited by 713
Hahn-Holbrook, J., Cornwell-Hinrichs, T., & Anaya, I. (2018) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2017.00248 · Cited by 667
Craske, M. G., Stein, M. B., Eley, T. C., Milad, M. R., Holmes, A., Rapee, R. M., & Wittchen, H.-U. (2017) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2017.24 · Cited by 652
Li, S. H., & Graham, B. M. (2017) · The Lancet Psychiatry · doi:10.1016/s2215-0366(16)30358-3 · Cited by 579
Galea, L. A. M., McEwen, B. S., Tanapat, P., Deak, T., Spencer, R. L., & Dhabhar, F. S. (1997) · Neuroscience · doi:10.1016/s0306-4522(97)00233-9 · Cited by 540
Ventral hippocampal lesions affect anxiety but not spatial learning
Bannerman, D. M., Grubb, M., Deacon, R. M. J., Yee, B. K., Feldon, J., & Rawlins, J. N. P. (2003) · Behavioural Brain Research · doi:10.1016/s0166-4328(02)00268-1 · Cited by 530
Kundakovic, M., Gudsnuk, K., Franks, B., Madrid, J., Miller, R. L., Perera, F. P., & Champagne, F. A. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1214056110 · Cited by 490
Regulation of adult neurogenesis by antidepressant treatment
Duman, R. (2001) · Neuropsychopharmacology · doi:10.1016/s0893-133x(01)00358-x · Cited by 463
Estrous cycle phase and gonadal hormones influence conditioned fear extinction
Milad, M. R., Igoe, S. A., Lebron-Milad, K., & Novales, J. E. (2009) · Neuroscience · doi:10.1016/j.neuroscience.2009.09.011 · Cited by 417
Reduced hippocampal volume and total white matter volume in posttraumatic stress disorder
Villarreal, G., Hamilton, D. A., Petropoulos, H., Driscoll, I., Rowland, L. M., Griego, J. A., Kodituwakku, P. W., Hart, B. L., Escalona, R., & Brooks, W. M. (2002) · Biological Psychiatry · doi:10.1016/s0006-3223(02)01359-8 · Cited by 382
Sex differences in anxiety and emotional behavior
Donner, N. C., & Lowry, C. A. (2013) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-013-1271-7 · Cited by 379
Sundström Poromaa, I., & Gingnell, M. (2014) · Frontiers in Neuroscience · doi:10.3389/fnins.2014.00380 · Cited by 291 · cited 1×
“…dynamically impact female brain morphology (Dubol et al., 2021; Woolley et al., 1990), function (Albert et al., 2015; Marrocco and McEwen, 2016; Sundstrom Poromaa and Gingnell, 2014), and neurochemistry (Barth et al., 2015), and are likely contributors to female-specific risks for…”
State-dependent changes in hippocampal grey matter in depression
Arnone, D., McKie, S., Elliott, R., Juhasz, G., Thomas, E. J., Downey, D., Williams, S., Deakin, J. F. W., & Anderson, I. M. (2013) · Molecular Psychiatry · doi:10.1038/mp.2012.150 · Cited by 287
Deecher, D., Andree, T. H., Sloan, D., & Schechter, L. E. (2008) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2007.10.006 · Cited by 270
Population genetic study of the brain-derived neurotrophic factor (BDNF) gene
Petryshen, T. L., Sabeti, P. C., Aldinger, K. A., Fry, B., Fan, J. B., Schaffner, S. F., Waggoner, S. G., Tahl, A. R., & Sklar, P. (2010) · Molecular Psychiatry · doi:10.1038/mp.2009.24 · Cited by 267
Marcus, S. M., Kerber, K. B., Rush, A. J., Wisniewski, S. R., Nierenberg, A., Balasubramani, G. K., Ritz, L., Kornstein, S., Young, E. A., & Trivedi, M. H. (2008) · Comprehensive Psychiatry · doi:10.1016/j.comppsych.2007.06.012 · Cited by 266
Psychoplastogens: A promising class of plasticity-promoting neurotherapeutics
Olson, D. E. (2018) · Journal of Experimental Neuroscience · doi:10.1177/1179069518800508 · Cited by 257
Sex differences in the antidepressant-like effects of ketamine
Carrier, N., & Kabbaj, M. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2012.12.009 · Cited by 251
Gene regulation by gonadal hormone receptors underlies brain sex differences
Gegenhuber, B., Wu, M. V., Bronstein, R., & Tollkuhn, J. (2022) · Nature · doi:10.1038/s41586-022-04686-1 · Cited by 221
Bromis, K., Calem, M., Reinders, A. A. T. S., Williams, S. C. R., & Kempton, M. J. (2018) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2018.17111199 · Cited by 177
Marco, A., Meharena, H. S., Dileep, V., Raju, R. M., Davila-Velderrain, J., Zhang, A. L., Adaikkan, C., Young, J. Z., Gao, F., Kellis, M., et al. (2020) · Nature Neuroscience · doi:10.1038/s41593-020-00717-0 · Cited by 159
Sex differences in hippocampal function
Koss, W. A., & Frick, K. M. (2017) · Journal of Neuroscience Research · doi:10.1002/jnr.23864 · Cited by 156
Beagan, J. A., Pastuzyn, E. D., Fernandez, L. R., Guo, M. H., Feng, K., Titus, K. R., Chandrashekar, H., Shepherd, J. D., & Phillips-Cremins, J. E. (2020) · Nature Neuroscience · doi:10.1038/s41593-020-0634-6 · Cited by 143
Effect of menstrual cycle phase on corticolimbic brain activation by visual food cues
Frank, T. C., Kim, G. L., Krzemien, A., & Van Vugt, D. A. (2010) · Brain Research · doi:10.1016/j.brainres.2010.09.071 · Cited by 122
Inducible chromatin priming is associated with the establishment of immunological memory in T cells
Bevington, S. L., Cauchy, P., Piper, J., Bertrand, E., Lalli, N., Jarvis, R. C., Gilding, L. N., Ott, S., Bonifer, C., & Cockerill, P. N. (2016) · The EMBO Journal · doi:10.15252/embj.201592534 · Cited by 110
Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders
Hu, B., Won, H., Mah, W., Park, R. B., Kassim, B., Spiess, K., Kozlenkov, A., Crowley, C. A., Pochareddy, S., The PsychENCODE Consortium, et al. (2021) · Nature Communications · doi:10.1038/s41467-021-24243-0 · Cited by 103 · cited 1×
“…elements and is also thought to play an important role in dynamic transcriptional regulation in the brain (Beagan et al., 2020; Fernandez-Albert et al., 2019; Harabula and Pombo, 2021; Marco et al., 2020) and has been implicated in psychiatric disorders (Girdhar et al., 2022; Hu et al., 2021).”
Zhang, J., Qu, Y., Chang, L., Pu, Y., & Hashimoto, K. (2019) · International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyz048 · Cited by 55
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Henderson, A., Gardani, M., Dyker, G., & Matthews, L. (2025) · Journal of Affective Disorders · doi:10.1016/j.jad.2024.11.033 · Cited by 12
Jallouli, S., Ghroubi, S., Ben Dhia, I., Sakka, S., Damak, M., Jaafar, B., Yahia, A., Elleuch, M. H., Mhiri, C., & Hammouda, O. (2025) · Neurological Research · doi:10.1080/01616412.2025.2484426 · Cited by 2
Metadata
- Authors
- Kundakovic, M., & Rocks, D.
- Venue
- Frontiers in Neuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2022-07
- Volume
- 66
- Pages
- 101010
- ISSN
- 0091-3022 (ISSN-L)
- OpenAlex
- W4282923728
- Cited by
- 317
- References
- 41
- FWCI
- 33.25
- Type
- journal article
- Language
- en
- Open access
- hybrid
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