Preclinical sex differences in depression and antidepressant response: implications for clinical research
Open accessAbstract
Women suffer from depression and anxiety disorders more often than men, and as a result they receive antidepressants to a greater extent. Sex differences in antidepressant response in humans have been modestly studied, and results have been controversial. At the same time, preclinical studies on animal models of depression and antidepressant response have provided insights with regard to sex differences that could be useful for the design and interpretation of future clinical trials. This Mini-Review discusses such sex-differentiated findings with regard to the presentation of depression, endophenotypes, and antidepressant response. In particular, men and women differ in symptomatology of depression, and animal models of depression have revealed sex differences in behavioral indices. However, although in experimental studies behavioral indices and models are adjusted to identify sex differences properly, this is not the case in the use of depression rating scales in clinical studies. Accordingly, preclinical studies highlight the importance of sex differences at the baseline behavioral response and the underlying mechanisms that often converge after antidepressant treatment. This is also a neglected issue in human studies. Finally, preclinical research suggests that, in the quest for potential biomarkers for depression, sex should be an important factor to consider. Careful consideration of sex differences in preclinical research could facilitate and ameliorate the design and quality of clinical studies for disease biomarkers and novel fast-acting antidepressants that are so essential for both men and women suffering from depression. © 2016 Wiley Periodicals, Inc.
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Neurobiological research in animal models is biased toward males.
“Neurobiological research in animal models is biased toward males (80).”
From Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics. (2021) · cites this paper as [80]
The Significance passage says research often fails to consider gender, and the Presentation of Disease section describes animal-model measures routinely suited to males but not females (page numbers unavailable in our copy). These passages show male-oriented methods in depression research, but they do not establish that neurobiological animal-model research generally uses more males than females. (LLM, conf=0.76)
Experimental — accuracy not yet measuredWomen with depression and anxiety are more likely to have increased appetite and weight gain than male counterparts.
“Women with depression and anxiety are more likely to have increased appetite and weight gain than male counterparts [150], an outcome associated with the effects of stress to stimulate palatable food intake [119].”
From The menace of obesity to depression and anxiety prevalence (2022) · cites this paper as [150]
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- Authors
- Kokras, N., & Dalla, C.
- Affiliations
- National and Kapodistrian University of Athens (GR)
- Corresponding author
- Dalla, Christina
- Venue
- Journal of Neuroscience Research
- Publisher
- Wiley
- Published
- 2016-11-07
- Volume
- 95
- Issue
- 1-2
- Pages
- 731-736
- ISSN
- 0360-4012 (ISSN-L)
- 1097-4547
- OpenAlex
- W2550356572
- Cited by
- 94
- References
- 76
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 7 · 2023: 10 · 2022: 10 · 2021: 12 · 2020: 15 · 2019: 12 · 2018: 12 · 2017: 8
- FWCI
- 1.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- IKYDA 2015
- NK is supported from an IKY fellowship of excellence for postgraduate studies in Greece - Siemens Program.
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- sex differences, depression, antidepressant response, animal models of depression, endophenotypes, depressive symptoms, depression rating scales, biomarkers, clinical trial design, women's mental health, rapid-acting antidepressants
- MeSH terms
- Animals, Antidepressive Agents, Depression, Drug Evaluation, Preclinical, Humans
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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