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Sex differences in anxiety and depression clinical perspectives
Open accessAbstract
Sex differences are prominent in mood and anxiety disorders and may provide a window into mechanisms of onset and maintenance of affective disturbances in both men and women. With the plethora of sex differences in brain structure, function, and stress responsivity, as well as differences in exposure to reproductive hormones, social expectations and experiences, the challenge is to understand which sex differences are relevant to affective illness. This review will focus on clinical aspects of sex differences in affective disorders including the emergence of sex differences across developmental stages and the impact of reproductive events. Biological, cultural, and experiential factors that may underlie sex differences in the phenomenology of mood and anxiety disorders are discussed.
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“This result is consistent with previous studies showing that women experience anxiety more and are twice more likely to develop anxiety disorders over their lifetime than men [42].”
From Adaptive function and correlates of anxiety during a pandemic (2021) · cites this paper as [42]
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“with women at an increased risk (96, 97)”
From Higher Circulating Cortisol in the Follicular vs. Luteal Phase of the Menstrual Cycle: A Meta-Analysis (2020) · cites this paper as [96]
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“Other studies do not distinguish between gender and sex differences, 23 which may lead to ambiguity in the analysis.”
From Factors associated with gender and sex differences in anxiety prevalence and comorbidity: A systematic review (2022) · cites this paper as [23]
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“Notably, IDs are highly comorbid [17–19] with females [20–23] and young people (i.e. <65 years) [8, 10, 17–19, 22, 24–29] disproportionately affected.”
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“These findings are consistent with previous studies that females have shown higher rates of depressive symptoms (Kandel and Davies, 1982), generalized anxiety disorder (Altemus et al., 2014; Kessler et al., 1994), and suicidal ideation (Borges et al., 2006; Crosby et al., 1999).”
From Time in treatment: Examining mental illness trajectories across inpatient psychiatric treatment (2020) · cites this paper as Altemus et al., 2014
In the citing paper
“and surprising given that women are more susceptible to anxiety and depressive disorders than men (53).”
From Perineuronal nets, inhibitory interneurons and anxiety-related ventral hippocampal neuronal oscillations are altered by early life adversity (2019) · cites this paper as [53]
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BackgroundThe Persistence of Sex Bias in High-Impact Clinical Research
Barlek, M. H., Rouan, J. R., Wyatt, T. G., Helenowski, I., & Kibbe, M. R. (2022) · Journal of Surgical Research · doi:10.1016/j.jss.2022.04.077 · Cited by 34
Lobato, C. T., Camões, J., Carvalho, D. R., Vales, C., Dias, C. C., Gomes, E., & Araújo, R. (2022) · Journal of the Intensive Care Society · doi:10.1177/17511437221108904 · Cited by 34
Epidemiological overview of major depressive disorder in Scandinavia using nationwide registers
Pasman, J. A., Meijsen, J. J., Haram, M., Kowalec, K., Harder, A., Xiong, Y., Nguyen, T.-D., Jangmo, A., Shorter, J. R., Bergstedt, J., et al. (2023) · The Lancet Regional Health - Europe · doi:10.1016/j.lanepe.2023.100621 · Cited by 34
Domes, G., Linnig, K., & von Dawans, B. (2024) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2024.107004 · Cited by 40
“…stress on HPG functioning, evidence that women presenting a specific gonadal steroid profile tend to have and report a higher prevalence for some stress-related disorders (such as depression) supports the postulated connection between these two systems (Altemus et al., 2014; McHenry et al., 2014).”
Sex-stratified genome-wide association meta-analysis of major depressive disorder
Thomas, J. T., Thorp, J. G., Huider, F., Grimes, P. Z., Wang, R., Youssef, P., Coleman, J. R. I., Byrne, E. M., Adams, M. J., van Loo, H. M., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-63236-1 · Cited by 36
Woodward, E. M., & Coutellier, L. D. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.10.031 · Cited by 37
Synaptic Microenvironment in Depressive Disorder: Insights from Synaptic Plasticity
Ren, F., & Guo, R. (2021) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s268012 · Cited by 32
Zhang, X., Song, Y., Wei, Z., Chen, X., Zhuang, X., & Li, Y. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1120541 · Cited by 38
“, 2015), stress coping style (Altemus et al., 2014; Kiely et al., 2019) or fluctuations in exposure to reproductive hormones and peptides during the menstrual cycle (Altemus et al.”
BackgroundKazlauskas, E., Geležėlytė, O., Kvedaraitė, M., Ajduković, D., Johannesson, K. B., Böttche, M., Bondjers, K., Dragan, M., Figueiredo‐Braga, M., Grajewski, P., et al. (2023) · Journal of Affective Disorders · doi:10.1016/j.jad.2023.05.007 · Cited by 33
Danielsen, J. T., Strøm, L., Knutzen, S. M., Schmidt, H., Amidi, A., Wu, L. M., & Zachariae, R. H. (2023) · Psycho-Oncology · doi:10.1002/pon.6184 · Cited by 36
“However, we did not find a sex difference in rates of depression, even though rates of depression are generally higher among women than men in the general population.(70,71) With the exception of chemotherapy, no other treatment modality was associated with rates of depression or anxiety.”
BackgroundDisentangling sex differences in PTSD risk factors
Haering, S., Seligowski, A. V., Linnstaedt, S. D., Michopoulos, V., House, S. L., Beaudoin, F. L., An, X., Neylan, T. C., Clifford, G. D., Germine, L. T., et al. (2024) · Nature Mental Health · doi:10.1038/s44220-024-00236-y · Cited by 33
“Our findings are similar to previous research suggesting higher levels of these five constructs in women than in men 27–31 .”
Identification and analysis of the human sex-biased genes
Guo, S., Zhou, Y., Zeng, P., Xu, G., Wang, G., & Cui, Q. (2016) · Briefings in Bioinformatics · doi:10.1093/bib/bbw125 · Cited by 32
“Previous studies have highlighted a number of diseases influenced by sex, for instance, Takayasu’s arteritis [2], systemic lupus erythematosus [3, 4], rheumatoid arthritis [5], anxiety depressive disorders [6] and painful diseases [7] occurred predominantly in females, whereas abdominal aortic aneurysm [8], cardiovasc…”
BackgroundGilles, Y. D., & Polston, E. K. (2017) · Behavioural Brain Research · doi:10.1016/j.bbr.2017.03.036 · Cited by 33
Regenass, W., Möller, M., & Harvey, B. H. (2017) · Journal of Psychopharmacology · doi:10.1177/0269881117735769 · Cited by 33
Differential effects of chronic 17β‐oestradiol treatment on rat behaviours relevant to depression
Gogos, A., McCarthy, M., Walker, A. J., Udawela, M., Gibbons, A. S., Dean, B., & Kusljic, S. (2018) · Journal of Neuroendocrinology · doi:10.1111/jne.12652 · Cited by 34
“There was also a significant group x phase interaction (F (2,23)=3.”
BackgroundMethodInfluentialGoltermann, J., Redlich, R., Grotegerd, D., Dohm, K., Leehr, E. J., Böhnlein, J., Förster, K., Meinert, S., Enneking, V., Richter, M. F., et al. (2020) · Neuropsychopharmacology · doi:10.1038/s41386-020-00794-6 · Cited by 37
Drusch, S., Tri, T. L., Ankri, J., Zureik, M., & Herr, M. (2021) · BMC Geriatrics · doi:10.1186/s12877-021-02568-1 · Cited by 34
“The sex-difference in the prescription of BZDs may be related to the fact that women are more likely to be diagnosed with anxiety and mental disorders [28] and to seek health care than men [29].”
BackgroundAssociation Between Depressive Symptom Patterns and Clinical Profiles Among Persons Living with HIV
Chichetto, N. E., Okafor, C. N., Cook, R. L., Abraham, A. G., Bolan, R., & Plankey, M. W. (2017) · AIDS and Behavior · doi:10.1007/s10461-017-1822-6 · Cited by 33
“ferences in the prevalence and long-term severity of depressive symptoms [22].”
BackgroundPolacchini, A., Girardi, D., Falco, A., Zanotta, N., Comar, M., De Carlo, N. A., & Tongiorgi, E. (2018) · Neurobiology of Stress · doi:10.1016/j.ynstr.2018.02.002 · Cited by 30
“The finding that women are more susceptible to job-related psychosocial stress is in line with previous evidence showing a higher tendency for female to develop stress-related pathology such as anxiety and depression (Altemus et al., 2014).”
ResultPerceived chronic stress influences the effect of acute stress on cognitive flexibility
Knauft, K. M., Waldron, A., Mathur, M., & Kalia, V. (2021) · Scientific Reports · doi:10.1038/s41598-021-03101-5 · Cited by 40
Bitar, Z., Elias, M.-B., Malaeb, D. N., Hallit, S. R., & Obeïd, S. (2023) · BMC Psychology · doi:10.1186/s40359-023-01091-9 · Cited by 41
“These reproductive events lead to changes in hormones and hormonal metabolites, and therefore affect brain systems and mood regulation [49].”
BackgroundUnderstanding the heterogeneity of anxiety using a translational neuroscience approach
Drzewiecki, C. M., & Fox, A. S. (2024) · Cognitive Affective & Behavioral Neuroscience · doi:10.3758/s13415-024-01162-3 · Cited by 34
“There is substantial variability in clinical presentation across individuals (Altemus et al., 2014; Galatzer-Levy & Bryant, 2013; Lenze & Wetherell, 2011) (Fig.”
BackgroundHeart–Brain Axis: A Narrative Review of the Interaction between Depression and Arrhythmia
Fang, S., & Zhang, W. Y. (2024) · Biomedicines · doi:10.3390/biomedicines12081719 · Cited by 40
“Fluctuations in sex hormones among women are associated with an elevated risk of mood disorders such as depression [75].”
BackgroundInfluentialSpielberg, J. M., Schwarz, J. M., & Matyi, M. A. (2019) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2019.100791 · Cited by 37
“Indeed, a wealth of evidence indicates that rates of anxiety are approximately equal pre-adolescence, become significantly higher in females during adolescence, and remain so into adulthood (Altemus et al., 2014).”
BackgroundPass, L., Kennelty, K. A., & Carter, B. L. (2019) · BMJ Open · doi:10.1136/bmjopen-2019-029976 · Cited by 36
Wan, G., Tang, S., & Xu, Y. (2020) · Children and Youth Services Review · doi:10.1016/j.childyouth.2020.105266 · Cited by 32
The trace aminergic system: a gender-sensitive therapeutic target for IBS?
Pretorius, L., & Smith, C. (2020) · Journal of Biomedical Science · doi:10.1186/s12929-020-00688-1 · Cited by 32
“Here again, females are more at risk, with a significant female predominance reported for anxiety and depression-associated disorders [3].”
BackgroundMekhemar, M. K., Attia, S., Dörfer, C. E., & Conrad, J. (2021) · Biology · doi:10.3390/biology10070611 · Cited by 37
“This situation is explained by earlier findings that females are statistically more likely than men to acquire mental distress, depressive symptoms, and PTSD signs as adults [29,30].”
The sex-dependent response to psychosocial stress and ischaemic heart disease
Helman, T. J., Headrick, J. P., Stapelberg, N. J. C., & Braidy, N. (2023) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2023.1072042 · Cited by 36
Are cognitive aspects of defense a core feature of anxiety and depression?
Blanchard, D. C. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104947 · Cited by 31
Associations between cognitive and affective empathy and internalizing symptoms in late childhood
Bray, K. O., Anderson, V. A., Pantelis, C., Pozzi, E., Schwartz, O., Vijayakumar, N., Richmond, S., Deane, C., Allen, N. B., & Whittle, S. (2021) · Journal of Affective Disorders · doi:10.1016/j.jad.2021.04.034 · Cited by 33
Dai, W.-P., Huang, S., Luo, Y. M., Cheng, X. R., Xia, P., Yang, M., Zhao, P., Zhang, Y., Lin, W., & Ye, X. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.886916 · Cited by 33
Rattel, J. A., Wegerer, M., Miedl, S. F., Blechert, J., Grünberger, L. M., Craske, M. G., & Wilhelm, F. H. (2019) · Behaviour Research and Therapy · doi:10.1016/j.brat.2019.01.009 · Cited by 34
Restraint stress induced anxiety and sleep in mice
Xu, Y., Liu, G., Ji, Z.-Z., Li, Y.-Y., Wang, Y., Wu, X., Liu, J.-L., Ma, D.-X., Zhong, M., Gao, C., et al. (2023) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2023.1090420 · Cited by 31
Metadata
- Authors
- Altemus, M., Sarvaiya, N., & Neill Epperson, C.
- Affiliations
- Cornell University (US)
- Northwell Health (US)
- Corresponding author
- Altemus, Margaret
- ORCID
- Altemus, Margaret
- Venue
- Frontiers in Neuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2014-08
- Volume
- 35
- Issue
- 3
- Pages
- 320-330
- ISSN
- 0091-3022 (ISSN-L)
- PMC
- PMC4890708
- OpenAlex
- W2049163404
- Cited by
- 1,413
- References
- 176
- Citations by year
- 2026: 113 · 2025: 181 · 2024: 177 · 2023: 174 · 2022: 178 · 2021: 194 · 2020: 141 · 2019: 87 · 2018: 68 · 2017: 38 · 2016: 28 · 2015: 30 · 2014: 3
- FWCI
- 5.15
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Frontiers in Neuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health and NIH Office of Research on Women’s Health (P50 MH099910)
- National Institute on Drug Abuse (K24 DA03031)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Sex and Gender in Healthcare
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- sex differences, anxiety disorders, depression, mood disorders, reproductive hormones, reproductive events, stress responsivity, social expectations
- MeSH terms
- Animals, Anxiety, Anxiety Disorders, Depression, Humans, Sex Characteristics, Stress, Psychological
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