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Sex differences in stress-related psychiatric disorders: Neurobiological perspectives
Open accessAbstract
Stress is associated with the onset and severity of several psychiatric disorders that occur more frequently in women than men, including posttraumatic stress disorder (PTSD) and depression. Patients with these disorders present with dysregulation of several stress response systems, including the neuroendocrine response to stress, corticolimbic responses to negatively valenced stimuli, and hyperarousal. Thus, sex differences within their underlying circuitry may explain sex biases in disease prevalence. This review describes clinical studies that identify sex differences within the activity of these circuits, as well as preclinical studies that demonstrate cellular and molecular sex differences in stress responses systems. These studies reveal sex differences from the molecular to the systems level that increase endocrine, emotional, and arousal responses to stress in females. Exploring these sex differences is critical because this research can reveal the neurobiological underpinnings of vulnerability to stress-related psychiatric disorders and guide the development of novel pharmacotherapies.
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“the female gender was noted to have higher levels of depression, anxiety and stress as compared to the male gender.”
From Relationships between psychopathology, psychological process variables, and sociodemographic variables and comparison of quarantined and non-quarantined groups of malaysian university students in the covid-19 pandemic (2021) · cites this paper as [63]
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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 [97]
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“Similar trends were reported during previous pandemics [61,62,63,64].”
From Relationships between psychopathology, psychological process variables, and sociodemographic variables and comparison of quarantined and non-quarantined groups of malaysian university students in the covid-19 pandemic (2021) · cites this paper as [63]
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“Although at times conflicting, data from numerous studies have demonstrated notable sex differences with respect to stress‐induced cortisol levels 116, 117, 118.”
From History of early life adversity is associated with increased food addiction and sex-specific alterations in reward network connectivity in obesity (2019) · cites this paper as [118]
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“Males and females with MDD also differ in terms of activation of the HPA axis following stress.163”
From Epigenetic mechanisms of major depression: Targeting neuronal plasticity (2018) · cites this paper as [163]
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“Given the importance of the amygdala, hippocampus, and prefrontal cortex for stress responses and mood, 97-99 it is possible that anatomical differences in these regions may contribute to post-TBI symptoms, as women report greater anxiety and depression and men report more amnesia and confusion. 8,100,101”
From Sex Differences in Traumatic Brain Injury: What We Know and What We Should Know (2019) · cites this paper as [97]
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Gender Bias in Mental Health Disorders and Epidemiology of Psychiatric Disorders
Recio-Barbero, M., Romero-Jiménez, R., & Sáenz-Herrero, M. (2026) · Springer eBooks · doi:10.1007/978-3-032-17883-1_9
Gender Differences in Depressive Disorder
López-Zurbano, S. (2026) · Springer eBooks · doi:10.1007/978-3-032-17883-1_17
Sex Differences in Depression: Adult Cytogenesis as Potential Target for Precision Psychiatry
Rodrigues-Freitas, L., Pinto, L., & Canedo, T. (2026) · Cells · doi:10.3390/cells15121059
Ueno, H., Tanaka, Y., Kitano, E., Takahashi, Y., Mori, S., Murakami, S., Wani, K., Matsumoto, Y., Okamoto, M., & Ishihara, T. (2026) · Physiology & Behavior · doi:10.1016/j.physbeh.2026.115420
Metadata
- Authors
- Bangasser, D. A., & Valentino, R. J.
- Affiliations
- Temple University (US)
- Children's Hospital of Philadelphia (US)
- Venue
- Frontiers in Neuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2014-08
- Volume
- 35
- Issue
- 3
- Pages
- 303-319
- ISSN
- 0091-3022 (ISSN-L)
- PMC
- PMC4087049
- OpenAlex
- W2078229830
- Cited by
- 737
- References
- 350
- Citations by year
- 2026: 84 · 2025: 71 · 2024: 87 · 2023: 62 · 2022: 61 · 2021: 78 · 2020: 63 · 2019: 63 · 2018: 66 · 2017: 37 · 2016: 40 · 2015: 16 · 2014: 9
- FWCI
- 2.77
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Frontiers in Neuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- PHS
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Keywords
- sex differences, stress-related psychiatric disorders, post-traumatic stress disorder, depression, stress system, neuroendocrine stress response, corticolimbic circuitry, hyperarousal, sex differences in disease prevalence
- MeSH terms
- Animals, Arousal, Mental Disorders, Brain, Corticotropin-Releasing Hormone, Humans, Sex Characteristics, Stress, Psychological
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