ArticleACS chemical neuroscience2013
Chronic SSRI treatment exacerbates serotonin deficiency in humanized Tph2 mutant mice.
Article in ACS chemical neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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.
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Who cites it
25 citing papers in PubMed, 45 citations in OpenAlex.
- Trial
- An Open-Label Pilot Study of Combined Augmentation With Creatine Monohydrate and 5-Hydroxytryptophan for Selective Serotonin Reuptake Inhibitor- or Serotonin-Norepinephrine Reuptake Inhibitor-Resistant Depression in Adult Women.Journal of clinical psychopharmacology · 2017Trial
- The impact of paroxetine on insulin secretion and sensitivity through AKT/GLUT4 axis.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Fe(II) with Tris(1-pyrazolyl)methane Complex Increases Thermal Stability In Vitro and Activity In Vivo of the Mutant 447R Form of Mouse Tryptophan Hydroxylase 2.International journal of molecular sciences · 2026Article
- Serotonin dysfunction in ADHD.Journal of neurodevelopmental disorders · 2025Review
- What can the psychoneuroimmunology of yoga teach us about depression's psychopathology?Brain, behavior, & immunity - health · 2024Article
- Trace amine-associated receptor 1 agonist reduces aggression in brain serotonin-deficient tryptophan hydroxylase 2 knockout rats.Frontiers in psychiatry · 2024Article
- Organic cation transporter 2 contributes to SSRI antidepressant efficacy by controlling tryptophan availability in the brain.Translational psychiatry · 2023Article
- Aurantii fructus immaturus carbonisata-derived carbon dots and their anti-depression effect.Frontiers in molecular biosciences · 2023Article
- Mechanistic insights into the role of plant polyphenols and their nano-formulations in the management of depression.Frontiers in pharmacology · 2022Review
- Tryptophan Hydroxylase 2 Deficiency Modifies the Effects of Fluoxetine and Pargyline on the Behavior, 5-HT- and BDNF-Systems in the Brain of Zebrafish (International journal of molecular sciences · 2021Article
- Plasma metabolomic profiles associated with chronic distress in women.Psychoneuroendocrinology · 2021Article
- SSRIs: Applications in inflammatory lung disease and implications for COVID-19.Neuropsychopharmacology reports · 2021Review
- Constitutive Serotonin Tone Modulates Molecular and Behavioral Response to Chronic Fluoxetine Treatment: A Study on Genetic Rat Model.Frontiers in psychiatry · 2021Article
- An update on the treatment of premature ejaculation: A systematic review.Arab journal of urology · 2021Review
- Genetic Background Underlying 5-HTInternational journal of molecular sciences · 2020Article
- Slow-release delivery enhances the pharmacological properties of oral 5-hydroxytryptophan: mouse proof-of-concept.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2019Article
- Bacterial Lipopolysaccharide Increases Serotonin Metabolism in Both Medial Prefrontal Cortex and Nucleus Accumbens in Male Wild Type Rats, but Not in Serotonin Transporter Knockout Rats.Pharmaceuticals (Basel, Switzerland) · 2018Article
- From Serotonin to Neuroplasticity: Evolvement of Theories for Major Depressive Disorder.Frontiers in cellular neuroscience · 2017Review
- SSRI Augmentation by 5-Hydroxytryptophan Slow Release: Mouse Pharmacodynamic Proof of Concept.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2016Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 4 countries.
Funding
Abstract
Selective serotonin reuptake inhibitors (SSRIs) are a major class of antidepressants that act by blocking inward transport of serotonin (5-HT) into presynaptic neurons mediated by the serotonin transporter (SERT). Both reuptake and ongoing synthesis are essential in supporting intraneuronal serotonin concentrations in serotonergic neurons. A rare mutation in tryptophan hydroxylase 2 (Tph2), the rate limiting enzyme for 5-HT synthesis, was identified in several patients with major depression, and knock-in mice expressing the analogous mutation (R439H Tph2 KI) show 80% reduction in 5-HT synthesis and tissue levels. Chronic treatment with SSRIs (fluoxetine and paroxetine) resulted in a dramatic further depletion of 5-HT tissue levels in R439H Tph2 KI mice (down to 1-3% of wild type levels) while having little effects in wild-type controls. Treatment with the 5-HT precursor 5-hydroxytryptophan (5-HTP) restored 5-HT tissue content in mutant mice, and cotreatment with 5-HTP and fluoxetine essentially prevented the depleting effect of a chronic SSRI. These data demonstrate that chronic SSRI treatment could further exacerbate the 5-HT deficiency in Tph2 mutation carriers, and this can be prevented by 5-HTP supplementation.
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What OpenQuestion holds
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.