ArticleMolecular psychiatry2013
The evolutionary significance of depression in Pathogen Host Defense (PATHOS-D).
Article in Molecular psychiatry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02972554 (Beta-Blockers and Inflammatory Responses to Acute Psychosocial Stress), which is not on this map. Cited by 123 papers, 5 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Beta-Blockers and Inflammatory Responses to Acute Psychosocial Stress
Who cites it
123 citing papers in PubMed, 5 syntheses or guidelines pooled it, 248 citations in OpenAlex.
- Inflammation as a mediating pathway between social defeat and mental health in humans: A systematic review.Translational psychiatry · 2026Pooled it
- Peripheral Inflammatory Markers in Subtypes and Core Features of Depression: A Systematized Review.Psychopathology · 2023Pooled it
- Genetic Contributions of Inflammation to Depression.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2017Pooled it
- Pooled it
- Association of metabolically healthy obesity with depressive symptoms: pooled analysis of eight studies.Molecular psychiatry · 2014Pooled it
- The antidepressant effect of whole-body hyperthermia is associated with the classical interleukin-6 signaling pathway.Brain, behavior, and immunity · 2024Trial
- Integrating Ultimate and Proximate Explanations of Neurodivergence: Evolutionary Trade-Offs, Compensation, and Clinical Expression.Evolutionary applications · 2026Article
- Connection and communication between the nervous and immune systems.Nature reviews. Immunology · 2025Review
- The emergence of genetic variants linked to brain and cognitive traits in human evolution.Cerebral cortex (New York, N.Y. : 1991) · 2025Article
- Advancing an Inflammatory Subtype of Major Depression.The American journal of psychiatry · 2025Review
- Article
- Altered Brain Functional Connectivity and Peripheral Transcriptomic Profiles in Major Depressive Disorder With Childhood Maltreatment.Depression and anxiety · 2025Article
- The gut-brain-circadian axis in anxiety and depression: a critical review.Frontiers in psychiatry · 2025Review
- KETO-MOOD: Ketogenic Diet for Microbiome Optimization and Overcoming Depression - A Protocol for a Randomized Controlled Trial.Neuroimmunomodulation · 2025Article
- The Role of Insulin Within the Socio-Psycho-Biological Framework in Type 2 Diabetes-A Perspective from Psychoneuroimmunology.Biomedicines · 2024Review
- Periodontitis and Depressive Disorders: The Effects of Antidepressant Drugs on the Periodontium in Clinical and Preclinical Models: A Narrative Review.Journal of clinical medicine · 2024Review
- Psychotomimetic compensation versus sensitization.Pharmacology research & perspectives · 2024Review
- Article
- Annual Research Review: Neuroimmune network model of depression: a developmental perspective.Journal of child psychology and psychiatry, and allied disciplines · 2024Review
- Stressed to the Core: Inflammation and Intestinal Permeability Link Stress-Related Gut Microbiota Shifts to Mental Health Outcomes.Biological psychiatry · 2024Review
63 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Given the manifold ways that depression impairs Darwinian fitness, the persistence in the human genome of risk alleles for the disorder remains a much debated mystery. Evolutionary theories that view depressive symptoms as adaptive fail to provide parsimonious explanations for why even mild depressive symptoms impair fitness-relevant social functioning, whereas theories that suggest that depression is maladaptive fail to account for the high prevalence of depression risk alleles in human populations. These limitations warrant novel explanations for the origin and persistence of depression risk alleles. Accordingly, studies on risk alleles for depression were identified using PubMed and Ovid MEDLINE to examine data supporting the hypothesis that risk alleles for depression originated and have been retained in the human genome because these alleles promote pathogen host defense, which includes an integrated suite of immunological and behavioral responses to infection. Depression risk alleles identified by both candidate gene and genome-wide association study (GWAS) methodologies were found to be regularly associated with immune responses to infection that were likely to enhance survival in the ancestral environment. Moreover, data support the role of specific depressive symptoms in pathogen host defense including hyperthermia, reduced bodily iron stores, conservation/withdrawal behavior, hypervigilance and anorexia. By shifting the adaptive context of depression risk alleles from relations with conspecifics to relations with the microbial world, the Pathogen Host Defense (PATHOS-D) hypothesis provides a novel explanation for how depression can be nonadaptive in the social realm, whereas its risk alleles are nonetheless represented at prevalence rates that bespeak an adaptive function.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.