Evidence map›Paper›PMID 42888189›Full record

ArticleCommunications medicine2026

Immune-related gene expression links anxiety, depression, and pain outcomes in adolescence.

Anh Cong Tuan Le, Tobias Banaschewski, Arun L W Bokde, Rüdiger Brühl, Sylvane Desrivières, Hugh Garavan, Penny Gowland, Antoine Grigis, Andreas Heinz, Jean-Luc Martinot and 14 more

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Article in Communications medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

24 authors.

Anh Cong Tuan LeInstitute of Medical Psychology and Medical Sociology, University Medical Center Schleswig-Holstein, Kiel University, Kiel, Germany.ORCID http://orcid.org/0000-0003-2444-2711
Tobias BanaschewskiDepartment of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.ORCID http://orcid.org/0000-0003-4595-1144
Arun L W BokdeDiscipline of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.ORCID http://orcid.org/0000-0003-0114-4914
Rüdiger BrühlPhysikalisch-Technische Bundesanstalt (PTB), Braunschweig and Berlin, Berlin, Germany.ORCID http://orcid.org/0000-0003-0111-5996
Sylvane DesrivièresSocial, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.ORCID http://orcid.org/0000-0002-9120-7060
Hugh GaravanDepartments of Psychiatry and Psychology, University of Vermont, Burlington, VT, USA.ORCID http://orcid.org/0000-0002-8939-1014
Penny GowlandSir Peter Mansfield Imaging Centre School of Physics and Astronomy, University of Nottingham, University Park, Nottingham, UK.ORCID http://orcid.org/0000-0002-4900-4817
Antoine GrigisNeuroSpin, CEA, Université Paris-Saclay, Gif-sur-Yvette, France.
Andreas HeinzDepartment of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany.ORCID http://orcid.org/0000-0001-5405-9065
Jean-Luc MartinotInstitut National de la Santé et de la Recherce Médicale, INSERM U A10 "Trajectoires développementales & psychiatrie", University Paris-Saclay, Ecole Normale Supérieure Paris-Saclay, CNRS; Centre Borelli, Gif-sur-Yvette, France.ORCID http://orcid.org/0000-0002-0136-0388
Marie-Laure Paillère MartinotInstitut National de la Santé et de la Recherce Médicale, INSERM U A10 "Trajectoires développementales & psychiatrie", University Paris-Saclay, Ecole Normale Supérieure Paris-Saclay, CNRS; Centre Borelli, Gif-sur-Yvette, France.
Eric ArtigesInstitut National de la Santé et de la Recherce Médicale, INSERM U A10 "Trajectoires développementales & psychiatrie", University Paris-Saclay, Ecole Normale Supérieure Paris-Saclay, CNRS; Centre Borelli, Gif-sur-Yvette, France.ORCID http://orcid.org/0000-0003-4461-7646
Dimitri Papadopoulos OrfanosDepartment of Psychology, School of Social Sciences, University of Mannheim, 68131, Mannheim, Germany.ORCID http://orcid.org/0000-0002-1242-8990
Luise PoustkaDepartment of Child and Adolescent Psychiatry, Center for Psychosocial Medicine, University Hospital Heidelberg, Heidelberg, Germany.
Michael N SmolkaDepartment of Psychiatry and Psychotherapy, Technische Universität Dresden, Dresden, Germany.ORCID http://orcid.org/0000-0001-5398-5569
Nathalie HolzDepartment of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.ORCID http://orcid.org/0000-0002-6225-9267
Nilakshi VaidyaCentre for Population Neuroscience and Stratified Medicine (PONS), Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany.
Henrik WalterDepartment of Psychiatry and Psychotherapy CCM, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.ORCID http://orcid.org/0000-0002-9403-6121
Robert WhelanSchool of Psychology and Global Brain Health Institute, Trinity College Dublin, Dublin, Ireland.ORCID http://orcid.org/0000-0002-2790-7281
Paul WirschingDepartment of Psychiatry and Psychotherapy CCM, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.ORCID http://orcid.org/0000-0003-1228-6846
Gunter SchumannCentre for Population Neuroscience and Stratified Medicine (PONS), Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany.ORCID http://orcid.org/0000-0002-7740-6469
Herta FlorDepartment of Neuropsychology and Resilience Research, Research Group Learning and Brain Plasticity in Mental Disorders, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. herta.flor@zi-mannheim.de.ORCID http://orcid.org/0000-0003-4809-5398
Frauke NeesInstitute of Medical Psychology and Medical Sociology, University Medical Center Schleswig-Holstein, Kiel University, Kiel, Germany. Frauke.Nees@med.uni-muenchen.de.ORCID http://orcid.org/0000-0002-7796-8234
IMAGEN Consortium

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundChronic pain and internalising disorders such as anxiety and depression frequently co-occur during adolescence. Although prospective associations between internalising symptoms and later pain have been reported previously, the biological mechanisms underlying individual differences in this relationship remain poorly understood. Immune- and oxidative stress-related pathways, including the NRF2 gene, may contribute to such variability. This study investigated whether polymorphisms in the NRF2 gene (rs6721961 and rs35652124) are related to the association between anxiety and depression symptoms at age 14-15 and pain complaints two years later at age 16-17.

methodsData were drawn from the IMAGEN longitudinal study (N = 724). Anxiety and depression symptoms were assessed using the Development and Well-Being Assessment (DAWBA), and pain complaints were measured via the Children's Somatization Inventory (CSI). Genotyping was conducted for NRF2 SNPs rs6721961 and rs35652124. Regression analyses tested main effects, followed by genotype-stratified analyses.

resultsConsistent with previous literature, higher levels of anxiety and depression at age 14-15 predicted increased pain complaints at age 16-17. Carriers of the TG/TT genotype of rs6721961 had significantly lower anxiety scores and reported fewer pain complaints compared to those carrying the GG genotype of rs6721961. Notably, the association between anxiety and later pain was significant only among individuals with the GG genotype.

conclusionWhile replicating established associations between adolescent early internalising symptoms and later pain, this study suggests that genetic variation in NRF2 is related to the anxiety-pain association. Specifically, rs6721961 is associated with differences in susceptibility to pain among adolescents with elevated anxiety symptoms.

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PMID42888189

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