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Sex differences in anxiety and emotional behavior
Open accessAbstract
Research has elucidated causal links between stress exposure and the development of anxiety disorders, but due to the limited use of female or sex-comparative animal models, little is known about the mechanisms underlying sex differences in those disorders. This is despite an overwhelming wealth of evidence from the clinical literature that the prevalence of anxiety disorders is about twice as high in women compared to men, in addition to gender differences in severity and treatment efficacy. We here review human gender differences in generalized anxiety disorder, panic disorder, posttraumatic stress disorder and anxiety-relevant biological functions, discuss the limitations of classic conflict anxiety tests to measure naturally occurring sex differences in anxiety-like behaviors, describe sex-dependent manifestation of anxiety states after gestational, neonatal, or adolescent stressors, and present animal models of chronic anxiety states induced by acute or chronic stressors during adulthood. Potential mechanisms underlying sex differences in stress-related anxiety states include emerging evidence supporting the existence of two anatomically and functionally distinct serotonergic circuits that are related to the modulation of conflict anxiety and panic-like anxiety, respectively. We discuss how these serotonergic circuits may be controlled by reproductive steroid hormone-dependent modulation of crfr1 and crfr2 expression in the midbrain dorsal raphe nucleus and by estrous stage-dependent alterations of γ-aminobutyric acid (GABAergic) neurotransmission in the periaqueductal gray, ultimately leading to sex differences in emotional behavior.
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“Specifically, the left central amygdala is activated by stimuli and negative emotions in women, 39 while in men, it is activated by positive emotions. 64”
From Factors associated with gender and sex differences in anxiety prevalence and comorbidity: A systematic review (2022) · cites this paper as [64]
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“The results seem to indicate that gender socialization is, at least in part, responsible for the development of the psychosocial characteristics that act as risk factors for women and protective factors for men in the onset and course of anxiety.44,54,56,59,64,70”
From Factors associated with gender and sex differences in anxiety prevalence and comorbidity: A systematic review (2022) · cites this paper as [64]
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“Of the 44 documents, 31 were empirical/quantitative studies30–60 and 13 were reviews.61–73”
From Factors associated with gender and sex differences in anxiety prevalence and comorbidity: A systematic review (2022) · cites this paper as [64]
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“With respect to the latter, it has been pointed out that one of the possible explanations for differences in anxiety between the sexes resides in the brain regions relevant to emotions (i.e. fear) and their regulation, such as the hippocampus, amygdala, and prefrontal cortex.63,64”
From Factors associated with gender and sex differences in anxiety prevalence and comorbidity: A systematic review (2022) · cites this paper as [64]
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“(b) the fluctuations of sexual hormones that affect the anxious state of women,46,49,63,64,66,69”
From Factors associated with gender and sex differences in anxiety prevalence and comorbidity: A systematic review (2022) · cites this paper as [64]
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“(c) genetic factors.30,31,52,61,64,71”
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“The results from other studies also showed that women generally identified themselves with expressive or feminine traits such as kindness and sweetness, while men identified themselves with instrumental or masculine traits such as competitiveness, assertiveness, and self-confidence.59,64”
From Factors associated with gender and sex differences in anxiety prevalence and comorbidity: A systematic review (2022) · cites this paper as [64]
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“Importantly, women who scored higher on instrumentality reported lower subjective anxiety and less fear. 64”
From Factors associated with gender and sex differences in anxiety prevalence and comorbidity: A systematic review (2022) · cites this paper as [64]
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“With respect to femininity, the results showed contradictory information. While there are studies that have not found a relationship between femininity and anxiety, 64 other studies revealed that femininity accompanied by low self-esteem favored the development of anxiety.49,70”
From Factors associated with gender and sex differences in anxiety prevalence and comorbidity: A systematic review (2022) · cites this paper as [64]
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“Therefore, instrumentality mediates between anxiety and gender, not biological sex.”
From Factors associated with gender and sex differences in anxiety prevalence and comorbidity: A systematic review (2022) · cites this paper as [64]
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“Multiple researchers reported observing differential evaluation of sexual minority clients and patients such as these in multiple fields (Donner & Lowry, 2013;Henriques-Calado et al., 2014;Kress et al., 2022;LaRoche et al., 2015;Televantos & Strauss, 2022).”
From Examining Counselor Trainees’ Clinical Impressions of Pornography Use: Implications for Couple and Family Counselors (2026) · cites this paper as Donner & Lowry, 2013
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Metadata
- Authors
- Donner, N. C., & Lowry, C. A.
- Affiliations
- University of Colorado Boulder (US)
- Corresponding author
- Donner, Nina C.
- Venue
- Pflügers Archiv - European Journal of Physiology
- Published
- 2013-04-16
- Volume
- 465
- Issue
- 5
- Pages
- 601-626
- ISSN
- 0031-6768 (ISSN-L)
- 1432-2013
- PMC
- PMC3805826
- OpenAlex
- W2008301991
- Cited by
- 379
- References
- 404
- Citations by year
- 2026: 16 · 2025: 33 · 2024: 39 · 2023: 39 · 2022: 45 · 2021: 47 · 2020: 37 · 2019: 32 · 2018: 28 · 2017: 13 · 2016: 16 · 2015: 12 · 2014: 18 · 2013: 3
- FWCI
- 1.66
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Pflügers Archiv - European Journal of Physiology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (UL1TR001108)
- National Institute of Mental Health (F32MH084463, R01MH086539, R01MH065702)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- sex differences, anxiety disorders, generalized anxiety disorder, panic disorder, post-traumatic stress disorder, dorsal raphe nucleus, CRF1 receptor, CRF receptor 2, estrous cycle, GABAergic neurotransmission, periaqueductal gray, stress exposure, animal models of anxiety, emotional behavior
- MeSH terms
- Animals, Anxiety, Female, Humans, Male, Rodentia, Sex Characteristics, Stress Disorders, Post-Traumatic, Panic Disorder
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