ArticleMolecular psychiatry2016
TSPAN5, ERICH3 and selective serotonin reuptake inhibitors in major depressive disorder: pharmacometabolomics-informed pharmacogenomics.
Article in Molecular psychiatry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 2 of them syntheses that pooled it.
What it found
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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
73 citing papers in PubMed, 2 syntheses or guidelines pooled it, 118 citations in OpenAlex.
- Machine Learning and Pharmacogenomics at the Time of Precision Psychiatry.Current neuropharmacology · 2023Pooled it
- ERICH3: vesicular association and antidepressant treatment response.Molecular psychiatry · 2021Pooled it
- Trial
- Efficacy and safety of venlafaxine hydrochloride combined with tandospirone citrate for patients with vascular depression accompanied by somatic symptoms: An open-labeled randomized control trial.CNS neuroscience & therapeutics · 2024Trial
- Metabolomic signature of exposure and response to citalopram/escitalopram in depressed outpatients.Translational psychiatry · 2019Trial
- Can targeted metabolomics predict depression recovery? Results from the CO-MED trial.Translational psychiatry · 2019Trial
- The steroid metabolome in women with premenstrual dysphoric disorder during GnRH agonist-induced ovarian suppression: effects of estradiol and progesterone addback.Translational psychiatry · 2017Trial
- Nucleus accumbens CD81 regulates methamphetamine-induced locomotor activity, conditioned reward, and reinstatement in male and female rats.Psychopharmacology · 2026Article
- Decoding the serotonin-alcohol crosstalk: the role of central serotonergic dysregulation in alcohol use disorder.Pharmacological reports : PR · 2026Review
- Biomarker for craving and acamprosate treatment response in patients with alcohol use disorder: insights from multi-omics.Molecular psychiatry · 2026Article
- Exposome influences: a multi-omics perspective on the combined toxic effects of pharmaceuticals and personal care products in Alzheimer's disease.Frontiers in toxicology · 2026Review
- Article
- Impacts of Forest Bathing (Shinrin-Yoku) in Female Participants with Depression/Depressive Tendencies.Diseases (Basel, Switzerland) · 2025Article
- Pharmaco-Multiomics: A New Frontier in Precision Psychiatry.International journal of molecular sciences · 2025Review
- Comparing plasma levels and ratios of tryptophan, serotonin, kynurenine and quinolinic acid between patients with bipolar disorder and healthy controls: impact of depressive episode or post-traumatic stress disorder symptoms.Frontiers in psychiatry · 2025Article
- Plasma TREM2 levels, alcohol consumption, and liver enzymes in patients with alcohol use disorder: a sex-dependent relationship involving MS4A6A genetic polymorphism.Journal of proteomics and genomics research · 2025Article
- Age-dependent regulation of axoglial interactions and behavior by oligodendrocyte AnkyrinG.Nature communications · 2024Article
- Association of single nucleotide polymorphisms and gene-environment interactions with major depressive disorder in Chinese.Heliyon · 2024Article
- IL17RB genetic variants are associated with acamprosate treatment response in patients with alcohol use disorder: A proteomics-informed genomics study.Brain, behavior, and immunity · 2024Observational
- Long Non-Coding RNAs and Alzheimer's Disease: Towards Personalized Diagnosis.International journal of molecular sciences · 2024Article
13 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
20 authors at 6 institutions in 2 countries.
Funding
Abstract
Millions of patients suffer from major depressive disorder (MDD), but many do not respond to selective serotonin reuptake inhibitor (SSRI) therapy. We used a pharmacometabolomics-informed pharmacogenomics research strategy to identify genes associated with metabolites that were related to SSRI response. Specifically, 306 MDD patients were treated with citalopram or escitalopram and blood was drawn at baseline, 4 and 8 weeks for blood drug levels, genome-wide single nucleotide polymorphism (SNP) genotyping and metabolomic analyses. SSRI treatment decreased plasma serotonin concentrations (P<0.0001). Baseline and plasma serotonin concentration changes were associated with clinical outcomes (P<0.05). Therefore, baseline and serotonin concentration changes were used as phenotypes for genome-wide association studies (GWAS). GWAS for baseline plasma serotonin concentrations revealed a genome-wide significant (P=7.84E-09) SNP cluster on chromosome four 5' of TSPAN5 and a cluster across ERICH3 on chromosome one (P=9.28E-08) that were also observed during GWAS for change in serotonin at 4 (P=5.6E-08 and P=7.54E-07, respectively) and 8 weeks (P=1.25E-06 and P=3.99E-07, respectively). The SNPs on chromosome four were expression quantitative trait loci for TSPAN5. Knockdown (KD) and overexpression (OE) of TSPAN5 in a neuroblastoma cell line significantly altered the expression of serotonin pathway genes (TPH1, TPH2, DDC and MAOA). Chromosome one SNPs included two ERICH3 nonsynonymous SNPs that resulted in accelerated proteasome-mediated degradation. In addition, ERICH3 and TSPAN5 KD and OE altered media serotonin concentrations. Application of a pharmacometabolomics-informed pharmacogenomic research strategy, followed by functional validation, indicated that TSPAN5 and ERICH3 are associated with plasma serotonin concentrations and may have a role in SSRI treatment outcomes.
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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.