ArticleInternational journal of molecular sciences2021
Sex-Based Impact of Creatine Supplementation on Depressive Symptoms, Brain Serotonin and SSRI Efficacy in an Animal Model of Treatment-Resistant Depression.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- Pooled it
- Whey protein and creatine supplementation in autistic adult women: a call for sex- and age-specific research.Frontiers in nutrition · 2026Article
- Mental health of children in high-altitude regions: a bibliometric study and visualization analysis from 1979 to 2024.Annals of general psychiatry · 2025Article
- Novel Insights into Dietary Bioactive Compounds and Major Depressive Disorders: Evidence from Animal Studies and Future Perspectives.The Journal of nutrition · 2025Review
- From Stress to Synapse: The Neuronal Atrophy Pathway to Mood Dysregulation.International journal of molecular sciences · 2025Review
- Depression among Tibetan residents in the Southeastern region of Qinghai-Tibet plateau: a cross-sectional study.Scientific reports · 2025Article
- The role of brain creatine in behavioral health conditions.Frontiers in psychiatry · 2025Review
- Creatine Supplementation in Depression: A Review of Mechanisms, Efficacy, Clinical Outcomes, and Future Directions.Cureus · 2024Review
- The major biogenic amine metabolites in mood disorders.Frontiers in psychiatry · 2024Review
- Creatine Activity as a Neuromodulator in the Central Nervous System.Archives of Razi Institute · 2023Review
- St. John's wort (Hypericum perforatum) and depression: what happens to the neurotransmitter systems?Naunyn-Schmiedeberg's archives of pharmacology · 2022Review
- Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
backgroundRates of major depressive disorder (MDD) increase with living at altitude. In our model, rats housed at moderate altitude (in hypobaric hypoxia) exhibit increased depression-like behavior, altered brain serotonin and a lack of antidepressant response to most selective serotonin reuptake inhibitors (SSRIs). A forebrain deficit in the bioenergetic marker creatine is noted in people living at altitude or with MDD.
methodsRats housed at 4500 ft were given dietary creatine monohydrate (CRMH, 4%
resultsCRMH significantly improved brain creatine in a sex-based manner. At altitude, CRMH increased serotonin levels in the female prefrontal cortex and striatum but reduced male striatal and hippocampal serotonin. Dietary CRMH was antidepressant in the forced swim test and anti-anhedonic in the sucrose preference test in only females at altitude, with motor behavior unchanged. CRMH improved fluoxetine efficacy (20 mg/kg) in only males at altitude: CRMH + SSRI significantly improved male striatal creatine and serotonin vs. CRMH alone.
conclusionsDietary CRMH exhibits sex-based efficacy in resolving altitude-related deficits in brain biomarkers, depression-like behavior and SSRI efficacy, and may be effective clinically for SSRI-resistant depression at altitude. This is the first study to link CRMH treatment to improving brain serotonin.
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Registered trials
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