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 (592 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
Disorder in which five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure. Symptoms include: depressed mood most of the day, nearly every day; markedly diminished interest or pleasure in activities most of the day, nearly every day; significant weight loss when not dieting or weight gain; Insomnia or hypersomnia nearly every day; psychomotor agitation or retardation nearly every day; fatigue or loss of energy nearly every day; feelings of worthlessness or excessive or inappropriate guilt; diminished ability to think or concentrate, or indecisiveness, nearly every day; or recurrent thoughts of death, recurrent suicidal ideation without a specific plan, or a suicide attempt. (dsm-5)
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, Major; Disorder, Major Depressive; Disorders, Major Depressive; Major Depressive Disorders; Clinical Depression; Depressions, Clinical; Major Depression Disorder; Depression Disorders, Major.
Where it fits in the MeSH classification
- Broader topics
- Depressive Disorder
Related concepts
- Dsm-5
Research landscape
PubMed indexes 46,389 records tagged with the MeSH heading “Major Depressive Disorder” (counts retrieved 2026-10-31). 16,189 of them (34.9%) were published from 2020 onward, and the busiest period so far is 2010-2019 with 18,707 records.
Reviews account for 6,948 records (15.0%) and meta-analyses for 1,731. Randomized controlled trials number 4,571 (9.9%) as a share of all records on the topic. Randomized trials make up a comparatively large share of this literature, which means many treatment questions have been tested directly.
Show the data
| Period | Records |
|---|---|
| through 1999 | 625 |
| 2000-2009 | 10,868 |
| 2010-2019 | 18,707 |
| 2020 onward | 16,189 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 6,948 | 15.0% |
| Meta-analyses | 1,731 | 3.7% |
| Randomized controlled trials | 4,571 | 9.9% |
Method: PubMed query "Major 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 |
| Efficacy and target engagement of dopamine agonist pramipexole for anhedonic depression: a randomized placebo-controlled trial | 2026 | Randomized controlled trial Design not recorded in structured metadata | 4 | cc by PMID 42286321 · DOI · PMC13375643 |
| 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 |
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
Efficacy and target engagement of dopamine agonist pramipexole for anhedonic depression: a randomized placebo-controlled trial [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Anhedonia is a core and disabling symptom of mood disorders with limited treatment options.
- Closing excerpt
- gov identifiers: NCT05355337 and NCT05825235 .
- 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 (205 words)
Anhedonia is a core and disabling symptom of mood disorders with limited treatment options. We evaluated the efficacy and safety of the dopamine agonist pramipexole in patients with mood disorders characterized by clinically significant anhedonia. In this single-center, randomized, double-blind, placebo-controlled trial, adults with major depressive disorder, dysthymia or bipolar depression and elevated Snaith-Hamilton Pleasure Scale (SHAPS) scores were assigned (1:1) to flexible dose, once-daily oral pramipexole as add-on treatment or placebo for 9 weeks. The primary outcome was change in SHAPS score from baseline to week 9. Analyses were conducted in the modified intention-to-treat population. Eighty-five participants were randomized, and 82 were included in the analysis. The primary outcome was met: pramipexole was associated with a greater reduction in SHAPS scores compared to placebo (mean difference: -4.04, 95% confidence interval: -6.89 to -1.18, P = 0.006, Hedges' g = 0.62). Exploratory analyses indicated that pramipexole was associated with increased light physical activity and relative preservation of reward-related ventral striatal activation. Improvements in anhedonia were sustained during a 6-month open-label extension. Pramipexole was generally well tolerated compared to placebo. Pramipexole significantly improved anhedonia and showed a favorable safety profile, supporting its potential as an augmentation strategy in mood disorders. ClinicalTrials.gov identifiers: NCT05355337 and NCT05825235 .
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 42286321 · DOI · PMC13375643
Psilocybin-assisted therapy for treatment-resistant major depressive disorder in a public healthcare setting: a randomized controlled trial [3]
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
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 Effect of exercise for depression: systematic review and network meta-analysis of randomised controlled trials [4]
- Research article Exercise as medicine for depressive symptoms? A systematic review and meta-analysis with meta-regression [5]
- Research article Trans-ancestry genome-wide study of depression identifies 697 associations implicating cell types and pharmacotherapies [6]
- Research article Association of Depression and Cardiovascular Disease [7]
- Research article GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors [8]
- Research article Cell type specific transcriptomic differences in depression show similar patterns between males and females but implicate distinct cell types and genes [9]
Full-text reviews on EvidenceLib
Open-access review articles about this topic, reproduced in full with authors, licence and references.
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
- Ventorp F, Asp M, Olsson S, Lindahl J, Möller S, Svensson M, et al.. Efficacy and target engagement of dopamine agonist pramipexole for anhedonic depression: a randomized placebo-controlled trial. . 2026. PMID 42286321 · DOI · PMC13375643
- 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
- Noetel M, Sanders T, Gallardo-Gómez D, Taylor P, Del Pozo Cruz B, van den Hoek D, et al.. Effect of exercise for depression: systematic review and network meta-analysis of randomised controlled trials. BMJ. 2024. PMID 38355154 · DOI · PMC10870815
- Heissel A, Heinen D, Brokmeier LL, Skarabis N, Kangas M, Vancampfort D, et al.. Exercise as medicine for depressive symptoms? A systematic review and meta-analysis with meta-regression. Br J Sports Med. 2023. PMID 36731907 · DOI · PMC10423472
- 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
- Krittanawong C, Maitra NS, Qadeer YK, Wang Z, Fogg S, Storch EA, et al.. Association of Depression and Cardiovascular Disease. Am J Med. 2023. PMID 37247751 · DOI
- Docherty AR, Mullins N, Ashley-Koch AE, Qin X, Coleman JRI, Shabalin A, et al.. GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors. Am J Psychiatry. 2023. PMID 37777856 · DOI · PMC10603363
- Maitra M, Mitsuhashi H, Rahimian R, Chawla A, Yang J, Fiori LM, et al.. Cell type specific transcriptomic differences in depression show similar patterns between males and females but implicate distinct cell types and genes. Nat Commun. 2023. PMID 37217515 · DOI · PMC10203145
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.