Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 3 complete abstracts (577 words), 9 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Depressive Disorders; Disorder, Depressive; Disorders, Depressive; Depression Disorder; Disorders, Depression; Neurosis, Depressive; Depressive Neuroses; Neuroses, Depressive.
Where it fits in the MeSH classification
- Broader topics
- Mood Disorders
- Narrower topics
- Depression, Postpartum; Depressive Disorder, Treatment-Resistant; Dysthymic Disorder; Major Depressive Disorder; Premenstrual Dysphoric Disorder; Seasonal Affective Disorder; Vascular Depression
Research landscape
PubMed indexes 134,807 records tagged with the MeSH heading “Depressive Disorder” (counts retrieved 2026-10-31). 25,567 of them (19.0%) were published from 2020 onward, and the busiest period so far is 2010-2019 with 43,458 records.
Reviews account for 20,450 records (15.2%) and meta-analyses for 3,457. Randomized controlled trials number 10,086 (7.5%) as a share of all records on the topic.
Show the data
| Period | Records |
|---|---|
| through 1999 | 34,975 |
| 2000-2009 | 30,807 |
| 2010-2019 | 43,458 |
| 2020 onward | 25,567 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 20,450 | 15.2% |
| Meta-analyses | 3,457 | 2.6% |
| Randomized controlled trials | 10,086 | 7.5% |
Method: PubMed query "Depressive Disorder"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-31.
Reading the evidence in psychiatry and psychology
Research on mental health and behaviour relies on questionnaires, interviews and rating scales rather than physical measurements, so how a condition was defined and measured shapes every result. Many studies are observational or small, placebo responses can be large, and findings in one group or culture may not carry over to another. Nothing on this page is advice about diagnosis or treatment; anyone worried about their mental health should talk to a qualified clinician. Check how outcomes were measured, who took part and how long they were followed.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Distinguishing different psychiatric disorders using DDx-PRS | 2026 | Research article Design not recorded in structured metadata | 4 | cc by PMID 42625058 · DOI · PMC13559851 |
| Psilocybin-assisted therapy for treatment-resistant major depressive disorder in a public healthcare setting: a randomized controlled trial | 2026 | Randomized controlled trial Design not recorded in structured metadata | 2 | cc by PMID 42562964 · DOI · PMC13577891 |
| Dissecting pleiotropy between major depressive disorder and physical disease comorbidities | 2026 | Research article Design not recorded in structured metadata | 1 | cc by PMID 42649390 · DOI · PMC13553304 |
Distinguishing different psychiatric disorders using DDx-PRS [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Despite great progress on case-control polygenic prediction, an unmet need remains for a method that genetically distinguishes clinically related disorders (e.
- Closing excerpt
- True diagnosis probabilities in the top deciles of predicted diagnosis probabilities were considerably larger than prior baseline probabilities, implying appreciable potential for clinical utility in certain settings.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (179 words)
Despite great progress on case-control polygenic prediction, an unmet need remains for a method that genetically distinguishes clinically related disorders (e.g., schizophrenia (SCZ) versus bipolar disorder (BIP) versus major depressive disorder (MDD) versus controls). We introduce differential diagnosis-polygenic risk score (DDx-PRS), which jointly estimates the posterior probabilities of each diagnostic category (e.g., SCZ = 50%, BIP = 25%, MDD = 15%, control = 10%) by modeling variance-covariance structure across disorders, leveraging case-control polygenic risk scores and prior clinical probabilities for each diagnostic category. We applied DDx-PRS to Psychiatric Genomics Consortium SCZ, BIP, MDD and control data, including summary-level training data from three case-control genome-wide association studies (n = 41,917-173,140 cases; total n = 1,048,683) and held-out test data from different cohorts with equal numbers for each diagnostic category (total n = 11,460). DDx-PRS was well calibrated and well powered (consistent with simulations) and produced comparable results to methods that require tuning data. True diagnosis probabilities in the top deciles of predicted diagnosis probabilities were considerably larger than prior baseline probabilities, implying appreciable potential for clinical utility in certain settings.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 42625058 · DOI · PMC13559851
Psilocybin-assisted therapy for treatment-resistant major depressive disorder in a public healthcare setting: a randomized controlled trial [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Psilocybin-assisted therapy may be a promising new treatment for treatment-resistant depression.
- Closing excerpt
- : 2018-003573-97 .
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (208 words)
Psilocybin-assisted therapy may be a promising new treatment for treatment-resistant depression. We examined the feasibility of administering a single 25-mg dose of psilocybin or placebo with psychological support in a randomized controlled trial design with 6 weeks of follow-up. A two-arm, double-blind, randomized, placebo-controlled feasibility trial was conducted at one National Health Service (NHS) site in England. Eligible participants met Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for major depressive disorder and had an inadequate response to ≥2 antidepressant treatments or ≥1 antidepressant plus ≥1 psychotherapy. Participants received 25-mg psilocybin or placebo with preparation, dosing support and integration. Primary outcomes were recruitment, retention and estimation of the Montgomery-Åsberg Depression Rating Scale (MADRS) variance. A multilevel regression analysis with an intention-to-treat population was used. Sixty participants were randomized (1:1), balanced by age, sex and prior psilocybin exposure, and 59 of 60 participants completed the MADRS at all follow-up visits. The adjusted between-group difference at week 3 on the MADRS was -10.41 (95% confidence interval: -14.86 to -5.95; Cohen's d = -1.70), favoring psilocybin, which was sustained at week 6. In total, 123 and 164 nonserious adverse events occurred in the placebo and psilocybin arms, respectively. Findings support a future confirmatory trial. EudraCT no.: 2018-003573-97 .
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 42562964 · DOI · PMC13577891
Dissecting pleiotropy between major depressive disorder and physical disease comorbidities [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Major depressive disorder (MDD) is characterized by substantial comorbidity with medical conditions.
- Closing excerpt
- This work advances our understanding of MDD by highlighting unique and shared genetic components across different disease systems.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (190 words)
Major depressive disorder (MDD) is characterized by substantial comorbidity with medical conditions. To achieve better outcomes for patients with MDD, an improved understanding of the mechanisms underlying pervasive comorbidities is required. Here, to this end, we mapped patterns of pleiotropy by defining four clusters of physical diseases (cardiovascular, metabolic, gastrointestinal and immune) and analyzed their genetic relationships with MDD using genomic structural equation modeling. Three disease clusters exhibited independent associations with MDD and accounted for 47% of MDD h2SNP, with the gastrointestinal disease cluster having the strongest association (β = 0.63, s.e. = 0.05, P = 3.04 × 10-30). In addition, we identified independent loci associated with the shared genetic liability between each disease cluster and MDD, revealing different pleiotropic components. Characterization of these loci revealed previously unidentified associations with MDD and physical disease traits, along with unique biological pathways, drug groups, cell types and genes associated with each disease-MDD cluster. Our findings reveal genetic connections implicating the gut-brain axis as a key mechanism underlying the comorbidity of physical diseases in MDD. This work advances our understanding of MDD by highlighting unique and shared genetic components across different disease systems.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 42649390 · DOI · PMC13553304
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Trans-ancestry genome-wide study of depression identifies 697 associations implicating cell types and pharmacotherapies [4]
- Research article Resting-state network alterations in depression: a comprehensive meta-analysis of functional connectivity [5]
- Research article Esketamine Treatment for Depression in Adults: A PRISMA Systematic Review and Meta-Analysis [6]
- Research article Transcranial Electrical Stimulation in Treatment of Depression: A Systematic Review and Meta-Analysis [7]
- Research article Bright Light Therapy for Nonseasonal Depressive Disorders: A Systematic Review and Meta-Analysis [8]
- Research article Relative effectiveness of antidepressant treatments in treatment-resistant depression: a systematic review and network meta-analysis of randomized controlled trials [9]
Full-text reviews on EvidenceLib
Open-access review articles about this topic, reproduced in full with authors, licence and references.
Gut microbiota composition in depressive disorder: a systematic review, meta-analysis, and meta-regression
Mingxue Gao, Jizhi Wang, Penghong Liu et al. · Translational Psychiatry 2023 · CC BY 4.0
Physical Activity and Depressive Disorders in Pregnant Women—A Systematic Review
Daria Kołomańska, Marcin Zarawski, Agnieszka Mazur-Bialy · Medicina 2019 · CC BY 4.0
Major Depressive Disorder Is Associated with Impaired Interoceptive Accuracy: A Systematic Review
Michael Eggart, Andreas Lange, Martin J Binser et al. · Brain Sciences 2019 · CC BY 4.0
The molecular pathophysiology of depression and the new therapeutics
Haihua Tian, Zhenyu Hu, Jia Xu et al. · MedComm 2022 · CC BY 4.0
References
- Peyrot WJ, Panagiotaropoulou G, Olde Loohuis LM, Adams MJ, Andreassen OA, Awasthi S, et al.. Distinguishing different psychiatric disorders using DDx-PRS. . 2026. PMID 42625058 · DOI · PMC13559851
- Rucker JJ, Mantingh T, Kerr-Gaffney J, Bird C, Chu P, Modlin NL, et al.. Psilocybin-assisted therapy for treatment-resistant major depressive disorder in a public healthcare setting: a randomized controlled trial. . 2026. PMID 42562964 · DOI · PMC13577891
- Woodward DJ, Reay WR, Wormington B, Diaz-Torres S, Ong JS, Gerring ZF, et al.. Dissecting pleiotropy between major depressive disorder and physical disease comorbidities. . 2026. PMID 42649390 · DOI · PMC13553304
- Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium. Electronic address: andrew.mcintosh@ed.ac.uk, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium. Trans-ancestry genome-wide study of depression identifies 697 associations implicating cell types and pharmacotherapies. Cell. 2025. PMID 39814019 · DOI · PMC11829167
- Zhang Z, Zhang Y, Wang H, Lei M, Jiang Y, Xiong D, et al.. Resting-state network alterations in depression: a comprehensive meta-analysis of functional connectivity. Psychol Med. 2025. PMID 40008424 · DOI · PMC12080655
- Fountoulakis KN, Saitis A, Schatzberg AF. Esketamine Treatment for Depression in Adults: A PRISMA Systematic Review and Meta-Analysis. Am J Psychiatry. 2025. PMID 39876682 · DOI
- Ren C, Pagali SR, Wang Z, Kung S, Boyapati RB, Islam K, et al.. Transcranial Electrical Stimulation in Treatment of Depression: A Systematic Review and Meta-Analysis. JAMA Netw Open. 2025. PMID 40531534 · DOI · PMC12177679
- Menegaz de Almeida A, Aquino de Moraes FC, Cavalcanti Souza ME, Cavalcanti Orestes Cardoso JH, Tamashiro F, Miranda C, et al.. Bright Light Therapy for Nonseasonal Depressive Disorders: A Systematic Review and Meta-Analysis. JAMA Psychiatry. 2025. PMID 39356500 · DOI · PMC11447633
- Saelens J, Gramser A, Watzal V, Zarate CA, Lanzenberger R, Kraus C. Relative effectiveness of antidepressant treatments in treatment-resistant depression: a systematic review and network meta-analysis of randomized controlled trials. Neuropsychopharmacology. 2025. PMID 39739012 · DOI · PMC12032262
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-11-04; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-11-04.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.