Stress and Depression: Preclinical Research and Clinical Implications
Open accessAbstract
Major depression (MD) is a severe, lifethreatening, and highly prevalent psychiatric disorder, predicted to soon become one of the major causes of death worldwide.Despite extensive investigations, the exact mechanisms responsible for MD have not been identified.This Overview focuses on the role of stress in depression.It discusses current advancements in biological psychiatry, neuroscience, and neuroendocrinology, highlighting key findings presented in the research papers included in the Special Collection ''Stress-Induced Depression and Comorbidities: From Bench to Bedside,'' published in this issue of PLoS ONE.The Overview encompasses the problematic diagnosis of MD, as well as preclinical evidences linking genetic predisposition, early life events and social factors, imbalanced HPA axis, molecular pathways within the central nervous system, and metabolic comorbidities with depressionlike disorders.It is emphasized how the link between stress and depression can be deeper than previously recognized, following the description of a potentially common depression subtype, named tentatively ''stress-induced depression'' (STRID).Due to the inherent biological perspective underlying the STRID concept, both preclinical and clinical research will be pivotal in clarifying the validity of this new subtype of MD and in improving predictors for treatment response, and will provide a better basis for genetic studies as well as stimulating new drug discovery programs.
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Long-term stress increases the number of psychological difficulties and causes physical impairment.
“There is considerable evidence that long-term stress increases the number of psychological difficulties and causes physical impairment [2–5].”
From A pilot randomised trial comparing a mindfulness-based stress reduction course, a locally-developed stress reduction intervention and a waiting list control group in a real-life municipal health care setting (2020) · cites this paper as [4]
In “A Biological Pathogenesis: The Stress Model and HPA Axis Activity” (page unavailable), the paper says stress exposure conceivably plays a causal role in major depression and depression-like disorders. The “Stress-Induced Depression” section describes physical fatigue and sleep disturbance in affected patients, but the paper does not establish that long-term stress generally increases the number of psychological difficulties or causes physical impairment. (LLM, conf=0.84)
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- Authors
- Bartolomucci, A., & Leopardi, R.
- Affiliations
- University of Parma (IT)
- Karolinska Institutet (SE)
- Corresponding author
- Bartolomucci, Alessandro
- Leopardi, Rosario
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2009-01-30
- Volume
- 4
- Issue
- 1
- Pages
- e4265
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC2629543
- OpenAlex
- W2021956739
- Cited by
- 111
- References
- 77
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 6 · 2023: 6 · 2022: 6 · 2021: 5 · 2020: 12 · 2019: 11 · 2018: 5 · 2017: 4 · 2016: 6 · 2015: 9 · 2014: 10 · 2013: 6 · 2012: 5
- FWCI
- 2.30
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Karolinska Institutet
- Università degli Studi di Parma
- Deutsches Primatenzentrum
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- major depressive disorder, stress, stress-induced depression, hypothalamic-pituitary-adrenal axis, neuroendocrinology, genetic susceptibility, childhood adversity, social factors, metabolic comorbidities, depression diagnosis, treatment response prediction, depression subtypes, drug discovery
- MeSH terms
- Animals, Depressive Disorder, Humans, Stress, Psychological
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