Evidence map›Paper›PMID 41309559›Full record

ArticleTranslational psychiatry2025

The influence of CHRNA5 and D398N missense variation on social and emotional behaviors in rodents and humans.

F de Chaumont, R Icick, P Gorwood, S Granon, B Forget, C Bouarab, J Mattioni, T Bourgeron, U Maskos, N Ramoz and 1 more

Abstract read
In one paragraph

Article in Translational psychiatry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

11 authors.

F de Chaumont *Institut Pasteur, Université Paris Cité, CNRS, Human Genetics and Cognitive Functions, Paris, France.
R Icick *Département de Psychiatrie et de Médecine Addictologique, Site Lariboisière Fernand-Widal, GHU APHP.Nord, 200 rue du faubourg Saint-Denis, Paris, 75010, France. romain.icick@aphp.fr.ORCID http://orcid.org/0000-0002-5078-4048
P GorwoodUniversité Paris Cité, Institute of Psychiatry and Neuroscience of Paris (IPNP), INSERM U1266; GHU Paris Psychiatrie et Neurosciences, CMME, Hôpital Sainte-Anne, Paris, F-75014, France.ORCID http://orcid.org/0000-0003-1845-3676
S GranonInstitut des Neurosciences de Paris-Saclay, CNRS UMR 9197, Université Paris-Saclay, Paris, France.ORCID http://orcid.org/0000-0001-9384-3119
B ForgetInstitut Pasteur, Université Paris Cité, CNRS, Human Genetics and Cognitive Functions, Paris, France.ORCID http://orcid.org/0000-0002-5007-8004
C BouarabInstitut Pasteur, Université Paris Cité, Neurobiologie Intégrative des Systèmes Cholinergiques, CNRS UMR 3571, Paris, France.ORCID http://orcid.org/0000-0003-2498-5070
J MattioniUniversité Paris Cité, Institute of Psychiatry and Neuroscience of Paris (IPNP), INSERM U1266; GHU Paris Psychiatrie et Neurosciences, CMME, Hôpital Sainte-Anne, Paris, F-75014, France.ORCID http://orcid.org/0000-0003-3389-9932
T BourgeronInstitut Pasteur, Université Paris Cité, CNRS, Human Genetics and Cognitive Functions, Paris, France.
U MaskosInstitut Pasteur, Université Paris Cité, Neurobiologie Intégrative des Systèmes Cholinergiques, CNRS UMR 3571, Paris, France.ORCID http://orcid.org/0000-0002-2029-1437
N RamozUniversité Paris Cité, Institute of Psychiatry and Neuroscience of Paris (IPNP), INSERM U1266; GHU Paris Psychiatrie et Neurosciences, CMME, Hôpital Sainte-Anne, Paris, F-75014, France.ORCID http://orcid.org/0000-0002-8070-9938
M BessonInstitut Pasteur, Université Paris Cité, Neurobiologie Intégrative des Systèmes Cholinergiques, CNRS UMR 3571, Paris, France. morgane.besson@pasteur.fr.ORCID http://orcid.org/0000-0003-1381-7653

Funding

Institut Pasteur Programme Transversaux de Recherche NICOGNIBRAIN
6 · The paper itself

Abstract

Social behavior alterations, notably aggressivity-related behavioral states (ARBS), and substance use disorders (SUDs) show consistent associations. In psychopathology, ARBS and SUDs cluster together as externalizing disorders, which show evidence for shared genetic liability and are associated with emotional dysregulation. Human studies have identified a single nucleotide polymorphism (rs16969968) of CHRNA5 encoding the α5 subunit of nicotinic acetylcholine receptors (nAChRs) (hereafter called α5SNP) in association with nicotine dependence. The influence of α5 containing nAChRs (α5*nAChRs) and α5SNP on social behavior, ARBS and emotional regulation, promising endophenotypes for SUDs, remain to be characterized. We investigated dyadic and higher-level group social interactions, notably in response to nicotine, in rodents either knockout for Chrna5 or α5SNP carriers. We further conducted a genetic association study, in a student population, between α5SNP and a comprehensive set of ARBS-related psychometric items. Finally, we leveraged publicly-available findings from genome wise association studies (GWASs) to further characterize the link between α5SNP and ARBS. We show that α5*nAChRs modulate agonistic and dominance-like behaviors and nicotine's effects on these behaviors, and that α5SNP is associated with social alterations, in rodents. In students, α5SNP was associated with emotional dysregulation. This was partially supported by GWASs of ARBS-related traits, where associations were of small effect magnitude. The present results, by suggesting a novel role of α5*nAChRs and of the α5SNP in social -including ARBS- in rodents, and emotional dysregulation in humans, may serve as a basis to develop ligands targeting these receptors for treating ARBS, notably in the context of SUDs.

Indexed as

Behavior, AnimalEmotional RegulationEmotionsNerve Tissue ProteinsReceptors, NicotinicSocial BehaviorAdultAnimalsFemaleHumansMaleMiceMice, KnockoutMutation, MissenseNicotinePolymorphism, Single NucleotideCHRNA5 protein, humanCHRNA5 protein, mouseNerve Tissue ProteinsNicotineReceptors, Nicotinic

Identifiers

PMID41309559
PMCPMC12661019

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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.