Immune-related gene expression links anxiety, depression, and pain outcomes in adolescence
Year: 2026
Type: article
Abstract: Background: Chronic 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. Methods: Data 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. Results: Consistent 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. Conclusion: While 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.
Source: Communications Medicine
Authors: 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, Marie-Laure Paillère Martinot, Eric Artiges, Dimitri Papadopoulos Orfanos, Luise Poustka, Michael N. Smolka, Nathalie Holz, Nilakshi Vaidya, Henrik Walter, Robert Whelan, Paul Wirsching, Gunter Schumann, Herta Flor, Frauke Nees, Dimitri Papadopoulos Orfanos
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,690
OpenAlex ID: W7222500392