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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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Citations
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BackgroundInfluential
Cited by
Sorted by citations
Why is depression more common among women than among men?
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ResultIs oxytocin “nature’s medicine”
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BackgroundAnxiety, depression and stress during the COVID-19 pandemic: Results from a cross-sectional survey
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“…problems (e.g., anxiety, depression) than males with ASD (Kreiser & White, 2014), similar to well-documented sex-based patterns among typically-developing adolescents and adults (Allgood-Merten, Lewinsohn, & Hops, 1990; Altemus, Sarvaiya, & Neill Epperson, 2014; Kendler & Gardner, 2014).”
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“In addition, females are two to three times more likely to develop mental disorders such as depression or anxiety disorders (Altemus et al., 2014; Bekker and van Mens-Verhulst, 2007; Kessler et al., 2005).”
Use and Perceptions of Cannabidiol Products in Canada and in the United States
Goodman, S. E., Wadsworth, E., Schauer, G. L., & Hammond, D. G. (2020) · Cannabis and Cannabinoid Research · doi:10.1089/can.2020.0093 · Cited by 111
“36 Similar to previous research, CBD product use was also higher among younger adults, 24,25,33 with the highest use reported by those aged 26–35 years.”
Hatak, I., & Zhou, H. (2019) · Entrepreneurship Theory and Practice · doi:10.1177/1042258719867559 · Cited by 122
“If pregnancy occurs, estrogen and progesterone and various other hormones and peptides such as prolactin and oxytocin are produced (Altemus et al., 2014).”
BackgroundInfluentialSelf-esteem and mental health in adolescents – level and stability during a school year
Moksnes, U. K., & Reidunsdatter, R. J. (2019) · Norsk Epidemiologi · doi:10.5324/nje.v28i1-2.3052 · Cited by 129
“major stress exposure, family conflict) (46,47,49).”
Cielo, F., Ulberg, R., & Di Giacomo, D. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph18116067 · Cited by 106
“In any case, most studies indicate that females show higher psychological symptoms, such as anxiety and depression, than males [43].”
BackgroundWhy the estrous cycle matters for neuroscience
Rocks, D., Cham, H., & Kundaković, M. (2022) · Biology of Sex Differences · doi:10.1186/s13293-022-00466-8 · Cited by 115
“What we demonstrate, though, is that proper classification of females will show the same trend that we see in humans, which is that low-estrogenic female mice (diestrus) show higher anxiety indices than highestrogenic females (proestrus) and males, thus recreating the fact that sex hormone withdrawal in humans is a tr…”
BackgroundThe study of active avoidance: a platform for discussion
Diehl, M. M., Bravo-Rivera, C., & Quirk, G. J. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.09.010 · Cited by 95
Lasselin, J., Lekander, M., Axelsson, J., & Karshikoff, B. (2018) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2018.06.005 · Cited by 106
“First, disorders such as depression (Altemus et al., 2014), chronic pain (Mogil, 2012) and chronic fatigue (Faro et al., 2016) are over-represented amongst women.”
Liu, S., Yang, L., Zhang, C., Xu, Y., Cai, L., Ma, S., Wang, Y., Cai, Z., Du, H., Li, R., et al. (2021) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2021.03.014 · Cited by 122
Ching, S. M., Ng, K. Y., Lee, K. W., Yee, A. H. A., Lim, P. Y., Ranita, H., Devaraj, N. K., Ooi, P. B., & Cheong, A. T. (2021) · PLoS ONE · doi:10.1371/journal.pone.0257983 · Cited by 108
Inflaming sex differences in mood disorders
Rainville, J. R., & Hodes, G. E. (2018) · Neuropsychopharmacology · doi:10.1038/s41386-018-0124-7 · Cited by 112
Chromatin organization in the female mouse brain fluctuates across the oestrous cycle
Jarić, I., Rocks, D., Greally, J. M., Suzuki, M., & Kundaković, M. (2019) · Nature Communications · doi:10.1038/s41467-019-10704-0 · Cited by 102
Colorectal Cancer and Onset of Anxiety and Depression: A Systematic Review and Meta-Analysis
Cheng, V., Oveisi, N., McTaggart-Cowan, H. M., Loree, J. M., Murphy, R. A., & Vera, M. A. D. (2022) · Current Oncology · doi:10.3390/curroncol29110689 · Cited by 105
Hamidovic, A., Karapetyan, K., Serdarevic, F., Choi, S. H., Eisenlohr-Moul, T., & Pinna, G. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00311 · Cited by 99
Christian, C. A., Reddy, D. S., Maguire, J., & Forcelli, P. A. (2020) · Pharmacological Reviews · doi:10.1124/pr.119.017392 · Cited by 105
“Despite the high incidence of psychiatric comorbidities in epilepsy and the well established sex differences in anxiety and depression in the general population (Altemus et al., 2014), few studies have investigated sex differences in psychiatric comorbidities in epilepsy.”
BackgroundLee, S. Y., Ju, Y. J., Lee, J. E., Kim, Y. T., Hong, S., Choi, Y. J., Song, M. K., & Kim, H. Y. (2020) · Journal of Affective Disorders · doi:10.1016/j.jad.2020.03.069 · Cited by 102
Crescentini, C., Feruglio, S., Matiz, A., Paschetto, A., Vidal, E., Cogo, P. E., & Fabbro, F. (2020) · Frontiers in Psychology · doi:10.3389/fpsyg.2020.586074 · Cited by 100
Oxytocin and stress-related disorders: neurobiological mechanisms and treatment opportunities
Sippel, L. M., Allington, C. E., Pietrzak, R. H., Harpaz-Rotem, I., Mayes, L. C., & Olff, M. (2017) · Chronic Stress · doi:10.1177/2470547016687996 · Cited by 99
Social dominance mediates behavioral adaptation to chronic stress in a sex-specific manner
Karamihalev, S., Brivio, E., Flachskamm, C., Stoffel, R., Schmidt, M. V., & Chen, A. (2020) · eLife · doi:10.7554/elife.58723 · Cited by 98
Moser, J. S., Moran, T. P., Kneip, C., Schroder, H. S., & Larson, M. J. (2016) · Psychophysiology · doi:10.1111/psyp.12509 · Cited by 96
“Using metaanalysis, we show that the relationship between symptoms of anxiety and a neurophysiological marker of error monitoring—the error-related negativity (ERN)—is significantly greater in women than men such that women, but not men, with higher levels of anxiety show a larger ERN.”
Golberstein, E., Busch, S. H., Zaha, R. L., Greenfield, S. F., Beardslee, W. R., & Meara, E. R. (2014) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2014.14030375 · Cited by 96
Epperson, C. N., Sammel, M. D., Bale, T. L., Kim, D. R., Conlin, S. E., Scalice, S., Freeman, K., & Freeman, E. W. (2017) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.16m10662 · Cited by 98
Global Prevalence of Depression among Heart Failure Patients: A Systematic Review and Meta-Analysis
Moradi, M., Doostkami, M., Behnamfar, N., Rafiemanesh, H., & Behzadmehr, R. (2021) · Current Problems in Cardiology · doi:10.1016/j.cpcardiol.2021.100848 · Cited by 98
Alıcı, N. K., & Öztürk, E. (2021) · Perspectives In Psychiatric Care · doi:10.1111/ppc.12851 · Cited by 100
“These results can be expected because usually, females have higher anxiety levels and fear compared to males because of gender traits.(43) It can be explained due to the greater hippocampal activation in men which may sub‐serve an enhanced capacity for contextualizing fear‐related stimuli.”
BackgroundBrand, S., Kalak, N., Gerber, M., Clough, P., Lemola, S., Bahmani, D. S., Pühse, U., & Holsboer‐Trachsler, E. (2016) · Journal of Sports Sciences · doi:10.1080/02640414.2016.1167936 · Cited by 104
“In this respect, the present results are consistent with previous findings (Altemus et al., 2014; Armitage & Hoffmann, 2001; Brand et al., 2010b; Hyde et al., 2008), though again the present study expands upon previous research with evidence for children crossing into adolescence.”
BackgroundResultInfluentialKokras, N., & Dalla, C. (2017) · Journal of Neuroscience Research · doi:10.1002/jnr.23861 · Cited by 94
“It is now well known that women develop dementia, anxiety disorders, panic disorder, posttraumatic stress disorder, and major depression more frequently than men, although alcoholism is more frequent in men (Kessler, 2007; Wittchen et al., 2011; Altemus et al., 2014).”
BackgroundSex differences: Transcriptional signatures of stress exposure in male and female brains
Brivio, E., Lopez, J. P., & Chen, A. (2020) · Genes, Brain and Behavior · doi:10.1111/gbb.12643 · Cited by 95
Recent Perspectives on Sex Differences in Compulsion-Like and Binge Alcohol Drinking
Radke, A. K., Sneddon, E. A., Frasier, R. M., & Hopf, F. W. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22073788 · Cited by 91
Maternal diet disrupts the placenta-brain axis in a sex-specific manner
Ceasrine, A. M., Devlin, B. A., Bolton, J. L., Green, L. A., Jo, Y. C., Huynh, C., Patrick, B., Washington, K., Sánchez, C., Joo, F., et al. (2022) · Nature Metabolism · doi:10.1016/j.bbi.2022.07.117 · Cited by 104
Volanen, S.-M., Lassander, M., Hankonen, N., Santalahti, P., Hintsanen, M., Simonsen, N., Raevuori, A., Mullola, S., Vahlberg, T., But, A., et al. (2020) · Journal of Affective Disorders · doi:10.1016/j.jad.2019.08.087 · Cited by 93
“, 2017), other biological, psychological, and cultural factors (Altemus et al., 2014; Mendelson et al., 2010).”
BackgroundDraper, A., Koch, R. M., van der Meer, J. W., Apps, M. A. J., Pickkers, P., Husain, M., & van der Schaaf, M. E. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2017.231 · Cited by 94
“Finally, we tested only men, whereas clinical work indicates that motivational symptoms such as depression are more prone in woman (Altemus et al, 2014).”
Neuroanatomical morphometric characterization of sex differences in youth using statistical learning
Sepehrband, F., Lynch, K. M., Cabeen, R. P., González-Zacarías, C., Zhao, L., D’Arcy, M., Kesselman, C., Herting, M. M., Dinov, I. D., Toga, A. W., et al. (2018) · NeuroImage · doi:10.1016/j.neuroimage.2018.01.065 · Cited by 88
“…(ASD), attention deficit and hyperactivity disorder (ADHD) and oppositional defiant disorder are more common in males (Baron-Cohen et al., 2011; Munkvold et al., 2011; Nøvik et al., 2006); while depression and anxiety are more prevalent in females (Schuch et al., 2014; Altemus et al., 2014).”
Premenstrual Exacerbations of Mood Disorders: Findings and Knowledge Gaps
Kuehner, C., & Nayman, S. (2021) · Current Psychiatry Reports · doi:10.1007/s11920-021-01286-0 · Cited by 93
Poor sleep is related to lower emotional competence among adolescents
Brand, S., Kirov, R., Kalak, N., Gerber, M., Schmidt, N. B., Lemola, S., Correll, C. U., & Holsboer-Trachsler, E. (2016) · Behavioral Sleep Medicine · doi:10.1080/15402002.2015.1048450 · Cited by 89
“Thus, our sleep-related results do not mirror previous findings (Altemus et al., 2014; Armitage & Hoffmann, 2001; Hyde et al., 2008), although our findings do go beyond previous studies in that similar results were observed among adolescents, and we focused on emotional competencies, including empathy.”
ResultZuloaga, D. G., Heck, A., Guzman, R. M. D., & Handa, R. J. (2020) · Biology of Sex Differences · doi:10.1186/s13293-020-00319-2 · Cited by 99
Holzmann, I., da Silva, L. M., da Silva, J. A. C., Steimbach, V. M. B., & de Souza, M. M. (2015) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2015.07.003 · Cited by 92
Psychological therapies for the treatment of depression in chronic obstructive pulmonary disease
Pollok, J., van Agteren, J. E., Esterman, A. J., & Carson‐Chahhoud, K. (2019) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd012347.pub2 · Cited by 93
Anxiety and Depression in Chronic Obstructive Pulmonary Disease: Recognition and Management
Yohannes, A. M., Kaplan, A. G., & Hanania, N. A. (2018) · Cleveland Clinic Journal of Medicine · doi:10.3949/ccjm.85.s1.03 · Cited by 95
Sex Differences in Stress Response: Classical Mechanisms and Beyond
Hodes, G. E., Bangasser, D. A., Sotiropoulos, I., Kokras, N., & Dalla, C. (2023) · Current Neuropharmacology · doi:10.2174/1570159x22666231005090134 · Cited by 103
“Evidence that sex/gender can influence stress reactions comes, in part, from epidemiological data that reveal that disorders linked to stress hormone dysregulation occur at different rates in men and women [10].”
Background
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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