ArticleNature medicine2013
Acid sphingomyelinase-ceramide system mediates effects of antidepressant drugs.
Article in Nature medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 190 papers, 4 of them syntheses that pooled it.
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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
190 citing papers in PubMed, 4 syntheses or guidelines pooled it, 376 citations in OpenAlex.
- Antidepressants for COVID-19: A systematic review.Journal of affective disorders · 2022Pooled it
- The effect of antidepressants on the severity of COVID-19 in hospitalized patients: A systematic review and meta-analysis.PloS one · 2022Pooled it
- Association between antidepressant use and reduced risk of intubation or death in hospitalized patients with COVID-19: results from an observational study.Molecular psychiatry · 2021Pooled it
- Statins in Depression: An Evidence-Based Overview of Mechanisms and Clinical Studies.Frontiers in psychiatry · 2021Pooled it
- Efficacy and safety of adding fluoxetine to the treatment regimen of hospitalized patients with non-critical COVID-19 pneumonia: A double-blind randomized, placebo-controlled clinical trial.Neuropsychopharmacology reports · 2023Trial
- The effects of atorvastatin on emotional processing, reward learning, verbal memory and inflammation in healthy volunteers: An experimental medicine study.Journal of psychopharmacology (Oxford, England) · 2021Trial
- The role of sphingolipids in major depressive disorder and associated cognitive impairment: interactions with monoaminergic signaling, neuroinflammation, and neurogenesis.Molecular psychiatry · 2026Review
- RIFT: A Fractal-Holographic Theory of Consciousness and Autopoietic Control.Brain sciences · 2026Article
- Ceramides: A Biologically Attractive Lipid and Advances in Acquisition Strategies.Antioxidants (Basel, Switzerland) · 2026Review
- Spatial lipidomic and neuron-specific transcriptomic signatures in the nucleus accumbens reveal phospholipid dyshomeostasis in depression-related maladaptations.Translational psychiatry · 2026Article
- Zuclopenthixol inhibits residual activity of acid sphingomyelinase in Niemann pick disease type B: a case report with in vitro validation.Orphanet journal of rare diseases · 2026Article
- The Association Between Serum Vitamin D and Lipid Levels in Patients With Depression: A Cross-Sectional Study.Alpha psychiatry · 2026Article
- Article
- Changes of fatty acid metabolism in FA 26:0, FA 22:2 and FA 24:1 are associated with leukoaraiosis in the elderly.BMC geriatrics · 2026Article
- Sphingolipids in Emotional Well-Being.Journal of neurochemistry · 2026Review
- Gut Microbiome-Sphingolipid Metabolism-Brain Axis Interactions: Neuroprotective Effects of Amitriptyline as Functional Inhibitor of Acid Sphingomyelinase in a Mouse Model of Tauopathy.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026Article
- Stress Biology in Cancer: Neuroendocrine-Immune Mechanisms Linking Tumor Progression to Translational Interventions.Cancer communications (London, England) · 2026Review
- High-fat diet-driven gut microbial sphingolipid metabolic reprogramming is associated with stress susceptibility in CUMS rats.Frontiers in microbiology · 2026Article
- Ethnicity and antenatal maternal anxiety: associations with the human milk lipidome in a multi-ethnic Asian cohort.Frontiers in nutrition · 2026Article
- The physiological and pathological effects of sphingolipid metabolism and signaling in the central nervous system.Brain pathology (Zurich, Switzerland) · 2026Review
130 more citing papers are in PubMed but not listed here.
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Authors and funding
21 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Major depression is a highly prevalent severe mood disorder that is treated with antidepressants. The molecular targets of antidepressants require definition. We investigated the role of the acid sphingomyelinase (Asm)-ceramide system as a target for antidepressants. Therapeutic concentrations of the antidepressants amitriptyline and fluoxetine reduced Asm activity and ceramide concentrations in the hippocampus, increased neuronal proliferation, maturation and survival and improved behavior in mouse models of stress-induced depression. Genetic Asm deficiency abrogated these effects. Mice overexpressing Asm, heterozygous for acid ceramidase, treated with blockers of ceramide metabolism or directly injected with C16 ceramide in the hippocampus had higher ceramide concentrations and lower rates of neuronal proliferation, maturation and survival compared with controls and showed depression-like behavior even in the absence of stress. The decrease of ceramide abundance achieved by antidepressant-mediated inhibition of Asm normalized these effects. Lowering ceramide abundance may thus be a central goal for the future development of antidepressants.
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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.