Evidence map›Paper›PMID 37770441›Full record

ArticleTranslational psychiatry2023

Polygenic risk scores of lithium response and treatment resistance in major depressive disorder.

Ying Xiong, Robert Karlsson, Jie Song, Kaarina Kowalec, Christian Rück, Robert Sigström, Lina Jonsson, Caitlin C Clements, Evelyn Andersson, Julia Boberg and 4 more

Open access · goldAbstract read
In one paragraph

Article in Translational psychiatry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
2.4field-weighted citation impact, top 11% 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

4 citing papers in PubMed, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 6 institutions in 4 countries.

Ying XiongDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Robert KarlssonDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0002-8949-2587
Jie SongDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0002-7357-2136
Kaarina KowalecDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0003-3928-9879
Christian RückDepartment of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0002-8742-0168
Robert SigströmDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Lina JonssonDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Caitlin C ClementsDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0003-2278-6465
Evelyn AnderssonDepartment of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
Julia BobergDepartment of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
Cathryn M LewisSocial, Genetic and Developmental Psychiatry Centre, King's College London, London, UK.ORCID http://orcid.org/0000-0002-8249-8476
Patrick F SullivanDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Mikael Landén *Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0002-4496-6451
Yi Lu *Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. lu.yi@ki.se.ORCID http://orcid.org/0000-0001-9933-3654
Karolinska Institutet · SEKing's College London · GBSahlgrenska University Hospital · SEUniversity of Gothenburg · SEUniversity of North Carolina at Chapel Hill · USUniversity of Notre Dame · US

Funding

A Trans-Nordic Study of Extreme Major DepressionR01MH123724 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI PATRICK F SULLIVAN, Lu Yi · 2020 to 2026
$4.7M
5/7 Psychiatric Genomics Consortium: Advancing Discovery and ImpactR01MH124873 · NIMH · CARDIFF UNIVERSITY · PI LEWIS, CATHRYN, O'DONOVAN, MICHAEL · 2021 to 2025
$2.6M
NIMH NIH HHS R01 MH123724NIMH NIH HHS R01 MH124873
6 · The paper itself

Abstract

Treatment response and resistance in major depressive disorder (MDD) are suggested to be heritable. Due to significant challenges in defining treatment-related phenotypes, our understanding of their genetic bases is limited. This study aimed to derive a stringent definition of treatment resistance and to investigate the genetic overlap between treatment response and resistance in MDD. Using electronic medical records on the use of antidepressants and electroconvulsive therapy (ECT) from Swedish registers, we derived the phenotype of treatment-resistant depression (TRD) and non-TRD within ~4500 individuals with MDD in three Swedish cohorts. Considering antidepressants and lithium are first-line treatment and augmentation used for MDD, respectively, we generated polygenic risk scores (PRS) of antidepressants and lithium response for individuals with MDD and evaluated their associations with treatment resistance by comparing TRD with non-TRD. Among 1778 ECT-treated MDD cases, nearly all (94%) used antidepressants before their first ECT and the vast majority had at least one (84%) or two (61%) antidepressants of adequate duration, suggesting these MDD cases receiving ECT were resistant to antidepressants. We did not observe a significant difference in the mean PRS of antidepressant response between TRD and non-TRD; however, we found that TRD cases had a significantly higher PRS of lithium response compared to non-TRD cases (OR = 1.10-1.12 under various definitions). The results support the evidence of heritable components in treatment-related phenotypes and highlight the overall genetic profile of lithium-sensitivity in TRD. This finding further provides a genetic explanation for lithium efficacy in treating TRD.

Indexed as

Depressive Disorder, Treatment-ResistantElectroconvulsive TherapyMajor Depressive DisorderAntidepressive AgentsHumansLithiumAntidepressive AgentsLithium

Identifiers

PMID37770441
PMCPMC10539379
OpenAlexW4387127397

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.