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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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“Generally, there is considerable evidence that sex differences exist with respect to depression, anxiety, and emotional and behavioral difficulties (for reviews, see Altemus et al., 2016; Bor et al. 2014).”
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“ing styles, rumination, and have higher rates of comorbid mood disorders.(61,66) Males are more likely”
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“…augments sex differences in excitatory synapse genetic markers in the nucleus accumbens, at least as demonstrated to date (Brancato et al. 2017), a finding consistent with the sex differences in incidence and phenotype of stress-linked disorders such as depression and anxiety (Altemus et al. 2014).”
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“, sex chromosome (41, 42), reproductive hormone exposure (43)] and social factors (44).”
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“It is also unclear why stress-related psychiatric illness is significantly more common in women (Pratchett et al. 2010; Altemus et al. 2014; Maeng and Milad 2015).”
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“Considering that brain activity dysfunction may vary betweenmale and female subjects (Altemus et al., 2014; Bangasser & Valentino, 2014), we only recruited female patients to increase the homogeneity of this study.”
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“Some evidence has indicated an overall advantage for females on episodic memory tasks (see Asperholm et al., 2019 for meta-analysis and review); however, women are also twice as likely as men to experience MDD and report higher severity of symptoms (see Altemus et al., 2014, for review).”
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Hormonal Cycles, Brain Network Connectivity, and Windows of Vulnerability to Affective Disorder
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“Population-based studies have shown that girls are more prone to somatic disorders, depression, and anxiety, whereas boys are more prone to oppositional defiant disorder, conduct disorder, and attention-deficit/hyperactivity disorder (ADHD; Altemus et al., 2014; Martel, 2013).”
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“Furthermore, depression and anxiety are more prevalent in females (16), and brain connectivity patterns associated with mood disorder symptoms are greater in females (17).”
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“This is consistent with prior evidence suggesting an increased prevalence of psychological conditions in women (68,69).”
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“Thus, anxiety and depression are two examples of stressrelated psychopathology for which there are clear sex differences in presentation and prevalence (Altemus et al. 2014).”
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“However, it remains unclear what role gender has in affecting HRQOL, especially since gender is associated with more anxiety and depressive symptoms in general [69], as well as in our own cohort [31].”
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Women’s Coverage, Utilization, Affordability, And Health After The ACA: A Review Of The Literature
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Screening for Psychological Distress and Risk of Cardiovascular Disease and Related Mortality
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“Females reported higher prevalence of mental health problems than males on all included indicators (depression symptoms, period of low mood, self-harm, suicide thoughts, and suicide attempts) in both 2012 and 2019, in keeping with long-recognised differences (Altemus et al., 2014).”
BackgroundPandey, R., Gupta, S., Upadhyay, A., Gupta, R. P., Shukla, M., Mishra, R. C., Arya, Y. K., Singh, T., Niraula, S., Lau, J. Y. F., et al. (2020) · Australian & New Zealand Journal of Psychiatry · doi:10.1177/0004867420909524 · Cited by 62
“The frequencies of lifetime experiences of abuse, neglect and victimisation (JVQ) along with current emotional and behavioural problems (SDQ) and potential psychiatric diagnoses (YI-4R) were calculated and compared, using chi-square test, between (1) boys and girls, given known gender differences in prevalence of many…”
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van den Brink, G., Stapersma, L., Vlug, L. E., Rizopolous, D., Bodelier, A. G., van Wering, H., Hurkmans, P. C. W. M., Stuyt, R. J. L., Hendriks, D. M., van der Burg, J. A. T., et al. (2018) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.14832 · Cited by 61
“This is probably not a consequence of an IBD-specific cause, because it parallels the well-known gender differences in the general population.(67) We failed to find a significant association between steroid use and anxiety and/or depressive symptoms, which is in agreement with the finding from Reed-Knight et al(64) an…”
ResultZhu, J., Zhou, Y., Jin, B., & Shu, J. (2023) · Therapeutic Advances in Endocrinology and Metabolism · doi:10.1177/20420188231199359 · Cited by 72
Wang, P., Cao, J., Wang, H., Liang, L., Zhang, J., Lutz, B. M., Shieh, K.-R., Bekker, A., & Tao, Y. (2015) · Journal of Pain · doi:10.1016/j.jpain.2015.07.006 · Cited by 60
“15,51 (1) Placing reflex: The rat was held with hind limbs slightly lower than the forelimbs and the dorsal surfaces of the hind paws were brought into contact with the edge of a table.”
BackgroundFactors associated with poor sleep during menopause: results from the Midlife Women's Health Study
Smith, R. L., Flaws, J. A., & Mahoney, M. M. (2018) · Sleep Medicine · doi:10.1016/j.sleep.2018.01.012 · Cited by 60
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Lost in translation: How to upgrade fear memory research
Flores, Á., Fullana, M. À., Soriano-Mas, C., & Andero, R. (2018) · Molecular Psychiatry · doi:10.1038/s41380-017-0006-0 · Cited by 59
“Considerable evidence [20, 21] indicates that sex differences in fear processing should”
BackgroundGender roles in relation to symptoms of anxiety and depression among students and workers
Arcand, M., Juster, R., LUPIEN, S. J., & Marin, M. (2020) · Anxiety Stress & Coping · doi:10.1080/10615806.2020.1774560 · Cited by 64
Pitzer, C., Porta, C. L., Treede, R., & Tappe‐Theodor, A. (2018) · European Journal of Pain · doi:10.1002/ejp.1303 · Cited by 59
The Psychological Impact of the COVID-19 Pandemic on Dentists in Germany
Mekhemar, M. K., Attia, S., Dörfer, C. E., & Conrad, J. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10051008 · Cited by 62
Ovarian hormones, sleep and cognition across the adult female lifespan: An integrated perspective
Gervais, N. J., Mong, J. A., & Agnès Lacreuse, A. (2017) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2017.08.002 · Cited by 59
“However, other factors affect subjective sleep measures including depressed mood (Toffol et al., 2014), which is also more common in women (e.g., Altemus et al, 2014).”
BackgroundBrain tumor necrosis factor-α mediates anxiety-like behavior in a mouse model of severe obesity
Fourrier, C., Bosch‐Bouju, C., Boursereau, R., Sauvant, J., Aubert, A., Capuron, L., Ferreira, G., Layé, S., & Castanon, N. (2018) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2018.11.316 · Cited by 55
Sex differences in neurological and psychiatric disorders
Young, L. J., & Pfaff, D. W. (2014) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2014.05.005 · Cited by 59
“Finally Altemus, Epperson and Sarvaiya, review sex differences in anxiety and depressive disorders from a clinical perspective using developmental stages across the lifespan as an organizing principal (Altemus et al., 2014).”
Salahinejad, A., Attaran, A., Naderi, M., Meuthen, D., Niyogi, S., & Chivers, D. P. (2020) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2020.141633 · Cited by 57
Sex Differences in Depression and Anxiety
Pavlidi, P., Kokras, N., & Dalla, C. (2022) · Current topics in behavioral neurosciences · doi:10.1007/7854_2022_375 · Cited by 60
Profiling changes in cortical astroglial cells following chronic stress
Simard, S., Coppola, G., Rudyk, C., Hayley, S. P., McQuaid, R. J., & Salmaso, N. (2018) · Neuropsychopharmacology · doi:10.1038/s41386-018-0105-x · Cited by 65
“A growing body of literature has demonstrated important sex differences in the prevalence of mood and anxiety disorders, with females typically at higher risk [64, 65].”
BackgroundEggenberger, L., Fordschmid, C., Ludwig, C., Weber, S., Grub, J., Komlenac, N., & Walther, A. (2021) · Behavioral Sciences · doi:10.3390/bs11060083 · Cited by 53
Epilepsy and its neurobehavioral comorbidities: Insights gained from animal models
Löscher, W., & Stafstrom, C. E. (2022) · Epilepsia · doi:10.1111/epi.17433 · Cited by 61
Silva, R. C., Pisanu, C., Maffioletti, E., Menesello, V., Bortolomasi, M., Gennarelli, M., Baune, B. T., Squassina, A., & Minelli, A. (2023) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2023.07.012 · Cited by 53
Meaklim, H., Saunders, W. J., Byrne, M. L., Junge, M. F., Varma, P., Finck, W. A., & Jackson, M. L. (2023) · Journal of Affective Disorders · doi:10.1016/j.jad.2022.11.021 · Cited by 55
Schwartzman, J. M., & Corbett, B. A. (2020) · Research in Autism Spectrum Disorders · doi:10.1016/j.rasd.2020.101613 · Cited by 53
Gene regulatory mechanisms underlying sex differences in brain development and psychiatric disease
Manoli, D. S., & Tollkühn, J. (2018) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13564 · Cited by 58
Association between depression, anxiety and weight change in young adults
Sahle, B. W., Breslin, M. C., Sanderson, K. A., Patton, G. C., Dwyer, T., Venn, A., & Gall, S. (2019) · BMC Psychiatry · doi:10.1186/s12888-019-2385-z · Cited by 60
Sex differences in the medial prefrontal cortical glutamate system
Knouse, M. C., McGrath, A. G., Deutschmann, A. U., Rich, M. T., Zallar, L. J., Rajadhyaksha, A. M., & Briand, L. A. (2022) · Biology of Sex Differences · doi:10.1186/s13293-022-00468-6 · Cited by 61
Latham, R. M., Kieling, C., Arseneault, L., Rocha, T. B.-M., Beddows, A. V., Beevers, S. D., Danese, A., Oliveira, K. D., Kohrt, B. A., Moffitt, T. E., et al. (2021) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2021.03.042 · Cited by 54
The role of sex and gender in anxiety disorders: Being scared “like a girl”?
Hallers‐Haalboom, E. T., Maas, J., Kunst, L. E., & Bekker, M. H. J. (2020) · Handbook of clinical neurology · doi:10.1016/b978-0-444-64123-6.00024-2 · Cited by 52
Panzica, G., & Melcangi, R. C. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.04.017 · Cited by 52
Murphy, J., Viding, E., & Bird, G. (2019) · Psychological Review · doi:10.1037/rev0000158 · Cited by 52
“This could partly explain why mental illness often manifests during periods of physical change (Altemus et al., 2014) and why women, who experience more physical change than men, are more likely to experience mental illness (Whiteford et al., 2015).”
BackgroundGender-specific approach in psychiatric diseases: Because sex matters
Franceschini, A., & Fattore, L. (2021) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2021.173895 · Cited by 56
Young, D. R., Hong, B. D., Lo, T., Inzhakova, G., Cohen, D. A., & Sidell, M. A. (2021) · Preventive Medicine · doi:10.1016/j.ypmed.2021.106863 · Cited by 52
“Women exhibit higher levels of depression and anxiety than men (Altemus et al., 2014), and others have reported this trend continuing during the pandemic (Duncan et al.”
BackgroundJi, J., Zhang, Y., Ma, Y., Jia, L., Cai, M., Li, Z., Zhang, T., & Guo, C. (2024) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2024.1259290 · Cited by 51
Sexually Dimorphic Effects of Aromatase on Neurobehavioral Responses
Shay, D. A., Vieira‐Potter, V. J., & Rosenfeld, C. S. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00374 · Cited by 55
“Anxiety and depression are two of the most widely diagnosed mental illnesses today with women being more likely to be diagnosed than men (Altemus et al., 2014).”
BackgroundAnimal Models of Maternal Immune Activation in Depression Research
Ronovsky, M., Berger, S., Molz, B., Berger, A., & Pollak, D. D. (2015) · Current Neuropharmacology · doi:10.2174/1570159x14666151215095359 · Cited by 49
“Interestingly, although in the human population the percentage of women among all depressed patients is much higher, with females having twice the lifetime rate of developing depression [121], few studies in MIA animal models have investigated potential sex differences in the effect of MIA on the offspring behavioral…”
BackgroundSex Differences in BNST and Amygdala Activation by Contextual, Cued, and Unpredictable Threats
Urien, L., & Bauer, E. P. (2021) · eNeuro · doi:10.1523/eneuro.0233-21.2021 · Cited by 53
Fonseca‐Rodrigues, D., Amorim, D., Almeida, A., & Pinto‐Ribeiro, F. (2020) · Behavioural Brain Research · doi:10.1016/j.bbr.2020.113008 · Cited by 47
How early maternal deprivation changes the brain and behavior?
Čater, M., & Majdič, G. (2021) · European Journal of Neuroscience · doi:10.1111/ejn.15238 · Cited by 51
“Psychoneuroendocrinology, 30, 418– 430. Eklund, M. B., & Arborelius, L. (2006). Twice daily long maternal separations in Wistar rats decreases anxiety- like behaviour in females but does not affect males. Behavior and Brain Research, 172, 278– 285. Ellenbriek, B. A., & Cools, A. R. (1998). The neurodevelopment hypothe…”
BackgroundInfluentialMansfield, K. L., Newby, D., Soneson, E., Vaci, N., Jindra, C., Geulayov, G., Gallacher, J., & Fazel, M. S. (2021) · JCPP Advances · doi:10.1002/jcv2.12021 · Cited by 54
“Notably, female pupils were especially at increased risk of depression, consistent with other studies (Altemus et al., 2014).”
ResultCyberbullying and Mental Health in Adults: The Moderating Role of Social Media Use and Gender
Schodt, K. B., Quiroz, S. I., Wheeler, B. L., Hall, D. L., & Silva, Y. N. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.674298 · Cited by 52
Forest, G., Gaudreault, P., Michaud, F., & Green‐Demers, I. (2022) · Sleep Medicine · doi:10.1016/j.sleep.2022.07.020 · Cited by 55
Effects of maternal exposure to bisphenol AF on emotional behaviors in adolescent mice offspring
Gong, M., Huai, Z., Song, H. S., Cui, L., Guo, Q., Shao, J., Gao, Y., & Shi, H. (2017) · Chemosphere · doi:10.1016/j.chemosphere.2017.08.119 · Cited by 49
Gao, M., Gao, D., Sun, H. J., Cheng, X., An, L., & Qiao, M. (2021) · Frontiers in Public Health · doi:10.3389/fpubh.2021.596128 · Cited by 51
Le, A. A., Lauterborn, J. C., Jia, Y., Wang, W., Cox, C. D., Gall, C. M., & LYNCH, G. S. (2022) · Nature Neuroscience · doi:10.1038/s41593-021-01001-5 · Cited by 49
Sleep, premenstrual mood disorder, and women’s health
Meers, J. M., & Nowakowski, S. (2019) · Current Opinion in Psychology · doi:10.1016/j.copsyc.2019.09.003 · Cited by 48
Andersen, A. J., Mary‐Krause, M., Bustamante, J. J. H., Héron, M., Aarbaoui, T. E., & Melchior, M. (2021) · BMC Psychiatry · doi:10.1186/s12888-021-03383-z · Cited by 59
In multiple sclerosis anxiety, not depression, is related to gender
Théaudin, M., Romero, K., & Feinstein, A. (2016) · Multiple Sclerosis · doi:10.1177/1352458515588582 · Cited by 46
Liu, Z., Yin, R. L., Fan, Z., Fan, H., Wu, H., Shen, B., Wu, S., & Kuang, F. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.00670 · Cited by 48
“Women in general are also documented to be more prone to depression than men (9, 10, 23), and recent evidence (22) also showed the female PWE had a higher ratio of comorbid depressive symptoms than the male.”
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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