Evidence map›Paper›PMID 36422266›Full record

ArticleMetabolites2022

Investigation of Genetic Variants Associated with Tryptophan Metabolite Levels via Serotonin and Kynurenine Pathways in Patients with Bipolar Disorder.

Claudia Pisanu, Alessio Squassina, Pasquale Paribello, Stefano Dall'Acqua, Stefania Sut, Sofia Nasini, Antonella Bertazzo, Donatella Congiu, Anna Meloni, Mario Garzilli and 12 more

Open access · goldAbstract read
In one paragraph

Article in Metabolites, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.7field-weighted citation impact, top 30% 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

3 citing papers in PubMed, 6 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
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

22 authors at 3 institutions in 2 countries.

Claudia PisanuDepartment of Biomedical Science, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, 09042 Cagliari, Italy.ORCID 0000-0002-9151-4319
Alessio SquassinaDepartment of Biomedical Science, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, 09042 Cagliari, Italy.ORCID 0000-0001-7415-7607
Pasquale ParibelloUnit of Clinical Psychiatry, University Hospital Agency of Cagliari, 09121 Cagliari, Italy.ORCID 0000-0001-9953-6929
Stefano Dall'AcquaDepartment of Pharmaceutical and Pharmacological Sciences, University of Padua, 35131 Padua, Italy.ORCID 0000-0001-8264-6953
Stefania SutDepartment of Pharmaceutical and Pharmacological Sciences, University of Padua, 35131 Padua, Italy.
Sofia NasiniDepartment of Pharmaceutical and Pharmacological Sciences, University of Padua, 35131 Padua, Italy.ORCID 0000-0002-5821-9684
Antonella BertazzoDepartment of Pharmaceutical and Pharmacological Sciences, University of Padua, 35131 Padua, Italy.
Donatella CongiuDepartment of Biomedical Science, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, 09042 Cagliari, Italy.
Anna MeloniDepartment of Biomedical Science, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, 09042 Cagliari, Italy.
Mario GarzilliUnit of Clinical Psychiatry, University Hospital Agency of Cagliari, 09121 Cagliari, Italy.
Beatrice GuisoUnit of Clinical Psychiatry, University Hospital Agency of Cagliari, 09121 Cagliari, Italy.
Federico SupraniUnit of Clinical Psychiatry, University Hospital Agency of Cagliari, 09121 Cagliari, Italy.
Vittoria PulcinelliUnit of Clinical Psychiatry, University Hospital Agency of Cagliari, 09121 Cagliari, Italy.
Maria Novella IaselliUnit of Clinical Psychiatry, University Hospital Agency of Cagliari, 09121 Cagliari, Italy.
Ilaria PinnaUnit of Clinical Psychiatry, University Hospital Agency of Cagliari, 09121 Cagliari, Italy.
Giulia SomainiUnit of Clinical Psychiatry, University Hospital Agency of Cagliari, 09121 Cagliari, Italy.
Laura ArruUnit of Clinical Psychiatry, University Hospital Agency of Cagliari, 09121 Cagliari, Italy.
Carolina CorriasUnit of Clinical Psychiatry, University Hospital Agency of Cagliari, 09121 Cagliari, Italy.
Federica PinnaUnit of Clinical Psychiatry, University Hospital Agency of Cagliari, 09121 Cagliari, Italy.
Bernardo CarpinielloUnit of Clinical Psychiatry, University Hospital Agency of Cagliari, 09121 Cagliari, Italy.
Stefano ComaiDepartment of Pharmaceutical and Pharmacological Sciences, University of Padua, 35131 Padua, Italy.ORCID 0000-0002-5686-7194
Mirko ManchiaUnit of Clinical Psychiatry, University Hospital Agency of Cagliari, 09121 Cagliari, Italy.
University of Cagliari · ITUniversity of Padua · ITDalhousie University · CA

Funding

Brain and Behaviour Foundation 2017 Young Investigator Grant
6 · The paper itself

Abstract

The kynurenine pathway (KP) may play a role in the pathophysiology of bipolar disorder (BD). We conducted a genome-wide association study (GWAS) to identify genetic variants associated with the plasma levels of the metabolites of tryptophan (TRP) via the serotonin (5-HT) and kynurenine (KYN) pathways in 44 patients with BD and 45 healthy controls. We assessed whether variants that were differentially associated with metabolite levels based on the diagnostic status improved the prediction accuracy of BD using penalized regression approaches. We identified several genetic variants that were significantly associated with metabolites (5-HT, 5-hydroxytryptophan (5-HTP), TRP, and quinolinic acid (QA) or metabolite ratios (5-HTP/TRP and KYN/TRP) and for which the diagnostic status exerted a significant effect. The inclusion of genetic variants led to increased accuracy in the prediction of the BD diagnostic status. Specifically, we obtained an accuracy of 0.77 using Least Absolute Shrinkage and Selection Operator (LASSO) regression. The predictors retained as informative in this model included body mass index (BMI), the levels of TRP, QA, and 5-HT, the 5-HTP/TRP ratio, and genetic variants associated with the levels of QA (rs6827515, rs715692, rs425094, rs4645874, and rs77048355) and TRP (rs292212) or the 5-HTP/TRP ratio (rs7902231). In conclusion, our study identified statistically significant associations between metabolites of TRP via the 5-HT and KYN pathways and genetic variants at the genome-wide level. The discriminative performance of penalized regression models incorporating clinical, genetic, and metabolic predictors warrants a follow-up analysis of this panel of determinants.

Indexed as

bipolar disordergenome-wide association studyGWASkynurenic acidkynureninequinolinic acidSNPtryptophan

Identifiers

PMID36422266
PMCPMC9694761
OpenAlexW4309174103

What OpenQuestion holds

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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.