ReviewPhilosophical transactions of the Royal Society of London. Series B, Biological sciences2012
The 5-HT deficiency theory of depression: perspectives from a naturalistic 5-HT deficiency model, the tryptophan hydroxylase 2Arg439His knockin mouse.
Review in Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers, 3 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.
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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.
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Who cites it
94 citing papers in PubMed, 3 syntheses or guidelines pooled it, 182 citations in OpenAlex.
- Vitamin D and depression in adults: A systematic review.Biomolecules & biomedicine · 2025Pooled it
- Efficacy and safety of omega-3 fatty acids supplementation for anxiety symptoms: a systematic review and dose-response meta-analysis of randomized controlled trials.BMC psychiatry · 2024Pooled it
- The effects of selective serotonin reuptake inhibitors on memory functioning in older adults: A systematic literature review.Journal of psychopharmacology (Oxford, England) · 2022Pooled it
- The association between negative affect and prescription opioid misuse in patients with chronic pain: the mediating role of opioid craving.The journal of pain · 2014Trial
- Gut microbiota-driven metabolites modulate the development of stress-related mental disorders.Translational psychiatry · 2026Review
- Effect of tryptophan supplementation on performance, hormones, and behavioral trait in weaning pig and lactating sow.Journal of animal science and technology · 2026Article
- Review
- Metabolomics Network Analysis of Various Genotypes Associated with Schizophrenia Gene Variant.Metabolites · 2025Article
- Alterations of circulating exosomal microRNAs in an LPS-induced depression model of male mice: Potential role in the anti-depressive effects of acupuncture.Physiological reports · 2025Article
- The microbiota-gut-brain axis in depression: unraveling the relationships and therapeutic opportunities.Frontiers in immunology · 2025Review
- High Prevalence of Severe Depression in Mexican Patients Diagnosed with HIV Treated with Efavirenz and Atazanavir: Clinical Follow-Up at Four Weeks and Analysis of TPH2 SNPs.Journal of clinical medicine · 2024Article
- Documentary Analysis ofPharmaceuticals (Basel, Switzerland) · 2024Review
- Sex-specific expression of distinct serotonin receptors mediates stress vulnerability of adult hippocampal neural stem cells in mice.Cell reports · 2024Article
- Adenosine signaling: a potential therapeutic target for psychogenic erectile dysfunction.American journal of translational research · 2024Review
- Constipation is associated with depression of any severity, but not with suicidal ideation: insights from a large cross-sectional study.International journal of colorectal disease · 2023Article
- Emphasizing the Crosstalk Between Inflammatory and Neural Signaling in Post-traumatic Stress Disorder (PTSD).Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2023Review
- Molecular signalling during cross talk between gut brain axis regulation and progression of irritable bowel syndrome: A comprehensive review.World journal of clinical cases · 2023Review
- Persistent Symptoms and IFN-γ-Mediated Pathways after COVID-19.Journal of personalized medicine · 2023Article
- Effects of the Combination of theBiomolecules · 2023Article
- Neuroprotective Effect of WhiteFoods (Basel, Switzerland) · 2023Article
34 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
3 authors at 2 institutions in 1 country.
Funding
Abstract
A decreased level of brain 5-hydroxytryptamine (5-HT) has been theorized to be a core pathogenic factor in depression for half a century. The theory arose from clinical observations that drugs enhancing extracellular levels of 5-HT (5-HT(Ext)) have antidepressant effects in many patients. However, whether such drugs indeed correct a primary deficit remains unresolved. Still, a number of anomalies in putative biomarkers of central 5-HT function have been repeatedly reported in depression patients over the past 40 years, collectively indicating that 5-HT deficiency could be present in depression, particularly in severely ill and/or suicidal patients. This body of literature on putative 5-HT biomarker anomalies and depression has recently been corroborated by data demonstrating that such anomalies indeed occur consequent to severely reduced 5-HT(Ext) levels in a mouse model of naturalistic 5-HT deficiency, the tryptophan hydroxylase 2 His(439) knockin (Tph2KI) mouse. In this review, we will critically assess the evidence for 5-HT deficiency in depression and the possible role of polymorphisms in the Tph2 gene as a causal factor in 5-HT deficiency, the latter investigated from a clinical as well as preclinical angle.
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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.