Evidence map›Paper›PMID 33230203›Full record

SynthesisMolecular psychiatry2021

ERICH3: vesicular association and antidepressant treatment response.

Duan Liu, Yongxian Zhuang, Lingxin Zhang, Huanyao Gao, Drew Neavin, Tania Carrillo-Roa, Yani Wang, Jia Yu, Sisi Qin, Daniel C Kim and 11 more

Open access · hybridAbstract readMeta-Analysis
In one paragraph

Synthesis in Molecular psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.0field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
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  5. A specific negatively charged sequence confers intramolecular regulation on Munc13-1 function in synaptic exocytosis.Proceedings of the National Academy of Sciences of the United States of America · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors at 4 institutions in 4 countries.

Duan Liu *Division of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.ORCID http://orcid.org/0000-0003-1065-246X
Yongxian Zhuang *Division of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.
Lingxin ZhangDivision of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.
Huanyao GaoDivision of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.
Drew NeavinDivision of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.
Tania Carrillo-RoaDepartment of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.
Yani WangDivision of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.
Jia YuDivision of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.
Sisi QinDivision of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.
Daniel C KimDivision of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.ORCID http://orcid.org/0000-0003-0919-3569
Erica LiuDivision of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.
Thanh Thanh Le NguyenDivision of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.ORCID http://orcid.org/0000-0002-2281-6540
Joanna M BiernackaDepartment of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA.ORCID http://orcid.org/0000-0001-9350-4440
Rima Kaddurah-DaoukDepartment of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA.
Boadie W DunlopDepartment of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.ORCID http://orcid.org/0000-0002-4653-0483
W Edward CraigheadDepartment of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.ORCID http://orcid.org/0000-0001-9957-0027
Helen S MaybergDepartment of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.ORCID http://orcid.org/0000-0002-1672-2716
Elisabeth B BinderDepartment of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.ORCID http://orcid.org/0000-0001-7088-6618
Mark A FryeDepartment of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA.
Liewei WangDivision of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.
Richard M WeinshilboumDivision of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA. Weinshilboum.Richard@mayo.edu.ORCID http://orcid.org/0000-0002-4911-7985
Mayo Clinic · USEmory University · USDuke University · USMax Planck Institute of Psychiatry · DE

Funding

CTSA INFRASTRUCTURE FOR PEDIATRIC RESEARCHUL1RR025008 · NCRR · EMORY UNIVERSITY · PI STEPHENS, DAVID S · 2007 to 2011
$29.0M
X LINKED NYSTAGMUS SYNDROME WITH FEATURES OF ALBINISMM01RR000039 · NCRR · EMORY UNIVERSITY · PI VACCARINO, VIOLA · 1985 to 2007
$21.3M
Pharmacogenetics of Phase II Drug Metabolizing EnzymesU19GM061388 · NIGMS · MAYO CLINIC ROCHESTER · PI WANG, LIEWEI, WEINSHILBOUM, RICHARD M. · 2010 to 2014
$15.8M
Metabolomic Signatures for Disease Sub-classification and Target Prioritization in AMP-ADU01AG061359 · NIA · DUKE UNIVERSITY · PI KADDURAH-DAOUK, RIMA F, KASTENMULLER, GABI · 2018 to 2022
$10.0M
Special Scientific Procedures: Statistical Modeling CoreP50MH077083 · NIMH · EMORY UNIVERSITY · PI KUTNER, MICHAEL HENRY · 2006 to 2010
$9.3M
Electrophysiological Biomarkers to Optimize DBS for DepressionUH3NS103550 · NINDS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI MAYBERG, HELEN S, RIVA-POSSE, PATRICIO · 2017 to 2023
$7.7M
INHERITED VARIATIONS IN DRUG-METABOLIZING ENZYMESR01GM028157 · NIGMS · MAYO CLINIC ROCHESTER · PI WEINSHILBOUM, RICHARD M. · 1985 to 2019
$6.9M
Predictors of Treatment Response Relapse and Recurrence in Major DepressionR01MH080880 · NIMH · EMORY UNIVERSITY · PI CRAIGHEAD, W. EDWARD · 2008 to 2012
$6.6M
Metabolic Signatures Underlying Vascular Risk Factors for Alzheimer-type DementiasRF1AG051550 · NIA · DUKE UNIVERSITY · PI KADDURAH-DAOUK, RIMA F, KLING, MITCHEL ALLAN · 2015 to 2016
$6.3M
Metabolic Networks and Pathways in Alzheimer's DiseaseR01AG046171 · NIA · DUKE UNIVERSITY · PI KADDURAH-DAOUK, RIMA F · 2014 to 2017
$4.4M
Metabolomic Signatures Predictive of Outcomes to Treatments for Major DepressionR01MH108348 · NIMH · DUKE UNIVERSITY · PI DUNLOP, BOADIE W, KADDURAH-DAOUK, RIMA F · 2016 to 2019
$2.7M
Predoctoral Training Program in Molecular PharmacologyT32GM072474 · NIGMS · MAYO CLINIC ROCHESTER · PI KARNITZ, LARRY M · 2005 to 2020
$2.4M
NCRR NIH HHS M01 RR000039NCRR NIH HHS UL1 RR025008NIA NIH HHS R01 AG046171NIA NIH HHS RF1 AG051550NIA NIH HHS U01 AG061359NIGMS NIH HHS R01 GM028157NIGMS NIH HHS U19 GM061388NIMH NIH HHS P50 MH077083NIMH NIH HHS R01 MH080880NIMH NIH HHS R01 MH108348
6 · The paper itself

Abstract

Selective serotonin reuptake inhibitors (SSRIs) are standard of care for major depressive disorder (MDD) pharmacotherapy, but only approximately half of these patients remit on SSRI therapy. Our previous genome-wide association study identified a single-nucleotide polymorphism (SNP) signal across the glutamate-rich 3 (ERICH3) gene that was nearly genome-wide significantly associated with plasma serotonin (5-HT) concentrations, which were themselves associated with SSRI response for MDD patients enrolled in the Mayo Clinic PGRN-AMPS SSRI trial. In this study, we performed a meta-analysis which demonstrated that those SNPs were significantly associated with SSRI treatment outcomes in four independent MDD trials. However, the function of ERICH3 and molecular mechanism(s) by which it might be associated with plasma 5-HT concentrations and SSRI clinical response remained unclear. Therefore, we characterized the human ERICH3 gene functionally and identified ERICH3 mRNA transcripts and protein isoforms that are highly expressed in central nervous system cells. Coimmunoprecipitation identified a series of ERICH3 interacting proteins including clathrin heavy chain which are known to play a role in vesicular function. Immunofluorescence showed ERICH3 colocalization with 5-HT in vesicle-like structures, and ERICH3 knock-out dramatically decreased 5-HT staining in SK-N-SH cells as well as 5-HT concentrations in the culture media and cell lysates without changing the expression of 5-HT synthesizing or metabolizing enzymes. Finally, immunofluorescence also showed ERICH3 colocalization with dopamine in human iPSC-derived neurons. These results suggest that ERICH3 may play a significant role in vesicular function in serotonergic and other neuronal cell types, which might help explain its association with antidepressant treatment response.

Indexed as

Major Depressive DisorderAntidepressive AgentsGenome-Wide Association StudyHumansSelective Serotonin Reuptake InhibitorsSerotoninAntidepressive AgentsSelective Serotonin Reuptake InhibitorsSerotonin

Identifiers

PMID33230203
PMCPMC8141066
OpenAlexW3109944467

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Registered trials

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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.