Peer-reviewed article
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 et al. ·
Summary
Written by AI, not yet AICS's view · claude-haiku-4-5-20251001This study followed 724 adolescents from the IMAGEN longitudinal study to understand why anxiety and depression in early adolescence sometimes lead to pain complaints later. The researchers measured anxiety and depression at ages 14-15 and pain complaints at ages 16-17, and tested whether differences in a gene called NRF2 explained why some anxious adolescents developed pain and others did not. They found that adolescents with higher anxiety and depression did report more pain complaints two years later, and that certain genetic variations in NRF2 were associated with lower anxiety and fewer pain complaints. The strongest link between anxiety and later pain was only found in adolescents with one particular NRF2 genetic variant.
Key points
- Adolescents with higher anxiety and depression at age 14-15 had significantly more pain complaints at age 16-17
- Carriers of the TG/TT genotype of NRF2 rs6721961 had lower anxiety scores and fewer pain complaints than those with the GG genotype
- The link between anxiety and later pain was only significant among adolescents carrying the GG genotype of rs6721961
- Genetic variation in the NRF2 gene appears related to differences in susceptibility to developing pain among anxious adolescents
- The study involved 724 participants from the IMAGEN longitudinal cohort with assessments at two time points over two years
Limitations
The study identifies an association between genetic variation and the anxiety-pain relationship but does not establish causation or explain the biological mechanisms through which NRF2 polymorphisms influence this relationship. The findings are from one longitudinal cohort and require replication in other populations.
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.
Findings the Hub has extracted
Each claim below is labelled by its type of design and links back to this report.
- Intervention
- Genetic testing for NRF2 gene polymorphisms (rs6721961 and rs35652124) to determine if genetic variation explains individual differences in the association between anxiety/depression and pain
- Population
- 724 adolescents from the IMAGEN longitudinal study, assessed at ages 14-15 and 16-17
Key finding
Higher anxiety and depression at age 14-15 predicted increased pain complaints at age 16-17, consistent with previous research
Le et al. · PubMed (US National Library of Medicine) · 16 Oct 2026