ArticleFrontiers in psychiatry2024
Cross-continental environmental and genome-wide association study on children and adolescent anxiety and depression.
Article in Frontiers in psychiatry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed.
- From school climate to brain development: What the ABCD study reveals about the educational context of adolescence.Developmental cognitive neuroscience · 2026Review
- Illuminating the complex interplay of risk factors for depression symptoms within a large-scale US longitudinal cohort.Social psychiatry and psychiatric epidemiology · 2026Article
- Breaking Through Barriers: The Transformative Potential of Nanomedicine in Overcoming Drug Delivery Challenges for Psychiatric Disorders.CNS & neurological disorders drug targets · 2026Review
- Association and functional study ofWorld journal of psychiatry · 2025Article
- DSAM: A deep learning framework for analyzing temporal and spatial dynamics in brain networks.Medical image analysis · 2025Article
- Multimodal Brain Growth Patterns: Insights from Canonical Correlation Analysis and Deep Canonical Correlation Analysis with Auto-Encoder.Information (Basel) · 2025Article
- Understanding the interplay of Caesarean delivery and genetic influences on intelligence and anxiety traits in offspring findings from genome-wide association studies.European journal of obstetrics & gynecology and reproductive biology: X · 2025Review
- Potassium channels in depression: emerging roles and potential targets.Cell & bioscience · 2024Review
- Potassium channels in animal models of post-traumatic stress disorder: mechanistic and therapeutic implications.Frontiers in cellular neuroscience · 2024Article
- Adolescent brain maturation associated with environmental factors: a multivariate analysis.Frontiers in neuroimaging · 2024Article
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Abstract
Anxiety and depression in children and adolescents warrant special attention as a public health concern given their devastating and long-term effects on development and mental health. Multiple factors, ranging from genetic vulnerabilities to environmental stressors, influence the risk for the disorders. This study aimed to understand how environmental factors and genomics affect children and adolescents anxiety and depression across three cohorts: Adolescent Brain and Cognitive Development Study (US, age of 9-10; N=11,875), Consortium on Vulnerability to Externalizing Disorders and Addictions (INDIA, age of 6-17; N=4,326) and IMAGEN (EUROPE, age of 14; N=1888). We performed data harmonization and identified the environmental impact on anxiety/depression using a linear mixed-effect model, recursive feature elimination regression, and the LASSO regression model. Subsequently, genome-wide association analyses with consideration of significant environmental factors were performed for all three cohorts by mega-analysis and meta-analysis, followed by functional annotations. The results showed that multiple environmental factors contributed to the risk of anxiety and depression during development, where early life stress and school support index had the most significant and consistent impact across all three cohorts. In both meta, and mega-analysis, SNP rs79878474 in chr11p15 emerged as a particularly promising candidate associated with anxiety and depression, despite not reaching genomic significance. Gene set analysis on the common genes mapped from top promising SNPs of both meta and mega analyses found significant enrichment in regions of chr11p15 and chr3q26, in the function of potassium channels and insulin secretion, in particular Kv3, Kir-6.2, SUR potassium channels encoded by the KCNC1, KCNJ11, and ABCCC8 genes respectively, in chr11p15. Tissue enrichment analysis showed significant enrichment in the small intestine, and a trend of enrichment in the cerebellum. Our findings provide evidences of consistent environmental impact from early life stress and school support index on anxiety and depression during development and also highlight the genetic association between mutations in potassium channels, which support the stress-depression connection via hypothalamic-pituitary-adrenal axis, along with the potential modulating role of potassium channels.
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