DNA Methylation Differences Associated with Social Anxiety Disorder and Early Life Adversity
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA688716 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Social anxiety disorder (SAD) is a psychiatric disorder characterized by extensive fear in social situations. Multiple genetic and environmental factors are known to contribute to its pathogenesis. One of the main environmental risk factors is early life adversity (ELA). Evidence is emerging that epigenetic mechanisms such as DNA methylation might play an important role in the biological mechanisms underlying SAD and ELA. To investigate the relationship between ELA, DNA methylation, and SAD, we performed an epigenome-wide association study for SAD and ELA examining DNA from whole blood of a cohort of 143 individuals using DNA methylation arrays. We identified two differentially methylated regions (DMRs) associated with SAD located within the genes SLC43A2 and TNXB. As this was the first epigenome-wide association study for SAD, it is worth noting that both genes have previously been associated with panic disorder. Further, we identified two DMRs associated with ELA within the SLC17A3 promoter region and the SIAH3 gene and several DMRs that were associated with the interaction of SAD and ELA. Of these, the regions within C2CD2L and MRPL28 showed the largest difference in DNA methylation. Lastly, we found that two DMRs were associated with both the severity of social anxiety and ELA, however, neither of them was found to mediate the contribution of ELA to SAD later in life. Future studies are needed to replicate our findings in independent cohorts and to investigate the biological pathways underlying these effects.
2021-01-31 | GSE164056 | GEO
Project description:16S sequencing data used as pilot for Social Anxiety Disorder FMT study
| PRJEB68191 | ENA
Project description:Social anxiety disorder (SAD) is a psychiatric disorder characterized by severe fear in social situations and avoidance of these. Multiple genetic as well as environmental factors contribute to the etiopathology of SAD. One of the main risk factors for SAD is stress, especially during early periods of life (early life adversity; ELA). ELA leads to structural and regulatory alterations contributing to disease vulnerability. This includes the dysregulation of the immune response. However, the molecular link between ELA and the risk for SAD in adulthood remain largely unclear. Evidence is emerging that long-lasting changes of gene expression patterns play an important role in the biological mechanisms linking ELA and SAD. Therefore, we conducted a transcriptome study of SAD and ELA performing RNA sequencing in peripheral blood samples. Analyzing differential gene expression between individuals suffering from SAD with high or low levels of ELA and healthy individuals with high or low levels of ELA, 13 significantly differentially expressed genes (DEGs) were identified with respect to SAD whilst no significant differences in expression were identified with respect to ELA. The most significantly expressed gene was MAPK3 (p=0.003) being upregulated in the SAD group compared to control individuals. In contrary, weighted gene co-expression network analyses (WGCNA) identified only modules significantly associated with ELA (p≤0.05), not with SAD. Furthermore, analyzing interaction networks of the genes from the ELA-associated modules and the SAD-related MAPK3) revealed complex interactions of those genes. Gene functional enrichment analyses indicate a role of signal transduction pathways as well as inflammatory responses supporting an involvement of the immune system in the association of ELA and SAD. In conclusion, we did not identify a direct molecular link between ELA and adult SAD by transcriptional changes. However, our data indicate an indirect association of ELA and SAD mediated by the interaction of genes involved in immune-related signal transduction.
2023-04-16 | GSE228702 | GEO
Project description:Social anxiety disorder (SAD) is a psychiatric disorder characterized by extensive fear in social situations. Multiple genetic and environmental factors are known to contribute to its pathogenesis. One of the main environmental risk factors is early life adversity (ELA). Evidence is emerging that epigenetic mechanisms such as DNA methylation might play an important role in the biological mechanisms underlying SAD and ELA. To investigate the relationship between ELA, DNA methylation, and SAD, we performed an epigenome-wide association study for SAD and ELA examining DNA from whole blood of a cohort of 143 individuals using DNA methylation arrays. We identified two differentially methylated regions (DMRs) associated with SAD located within the genes SLC43A2 and TNXB. As this was the first epigenome-wide association study for SAD, it is worth noting that both genes have previously been associated with panic disorder. Further, we identified two DMRs associated with ELA within the SLC17A3 promoter region and the SIAH3 gene and several DMRs that were associated with the interaction of SAD and ELA. Of these, the regions within C2CD2L and MRPL28 showed the largest difference in DNA methylation. Lastly, we found that two DMRs were associated with both the severity of social anxiety and ELA, however, neither of them was found to mediate the contribution of ELA to SAD later in life. Future studies are needed to replicate our findings in independent cohorts and to investigate the biological pathways underlying these effects.
| S-EPMC7862482 | biostudies-literature
Project description:The microbiome of patients with social anxiety disorder is altered in comparison to healthy controls
| PRJEB58864 | ENA
Project description:This study reveals a novel mechanism linking social isolation to anxiety through a glucocorticoid (GC)-driven, ventral hippocampal (vHip)-specific iron-α-synuclein (α-Syn) axis. Social isolation activates glucocorticoid receptors (GRs) in vHip pyramidal neurons, which upregulate transferrin receptor 1 (TfR1) to promote iron accumulation. Elevated iron induces α-Syn overexpression, thereby enhancing presynaptic glutamate release and neuronal hyperexcitability in the vHip; this ultimately drives anxiety-like behaviors. Gain-of-function/loss-of-function experiments confirm that TfR1 and α-Syn are essential for this pathway, while intranasal iron chelation or α-Syn inhibition rescues both neural and behavioral abnormalities. These findings establish the GR-TfR1-α-Syn axis as a therapeutic target for social stress-related anxiety, which bridges metallobiology and psychiatric pathophysiology.
2025-06-12 | GSE299293 | GEO
Project description:Molecular Portraits of Social Adversity in Breast Cancer
| PRJNA1229676 | ENA
Project description:Molecular Portraits of Social Adversity in Breast Cancer [RRBS]
| PRJNA1229682 | ENA
Project description:Adverse prenatal environment is a risk factor for the development of psychiatric disorders. Although studies have implicated epigenetic mechanisms, little is known about how epigenomic changes come about and lead to abnormal behaviors in affected individuals. We sought to identify epigenomic and transcriptomic signatures induced by a proinflammatory gestational environment in the ventral dentate gyrus (vDG), a hippocampal region linked to avoidance of threatening contexts, that persist and promote anxiety-like behavior in mice. Here we show that adversity shifted the methylation of enhancers and promoters with intermediate methylation and altered synapse-related gene expression, resulting in epigenetic and transcriptional heterogeneity in the vDG. Exposure to an anxiogenic environment recruited vDG neurons with the most transcriptional impact. Differentially expressed synapse-relevant genes in ensemble neurons tended to be differentially methylated. Finally, this ensemble exhibited higher activity in threatening than safe environment suggesting a prenatal adversity-induced epigenetic and neurobiological sequalae that leads to anxiety.
2025-07-31 | GSE284463 | GEO
Project description:Adverse prenatal environment is a risk factor for the development of psychiatric disorders. Although studies have implicated epigenetic mechanisms, little is known about how epigenomic changes come about and lead to abnormal behaviors in affected individuals. We sought to identify epigenomic and transcriptomic signatures induced by a proinflammatory gestational environment in the ventral dentate gyrus (vDG), a hippocampal region linked to avoidance of threatening contexts, that persist and promote anxiety-like behavior in mice. Here we show that adversity shifted the methylation of enhancers and promoters with intermediate methylation and altered synapse-related gene expression, resulting in epigenetic and transcriptional heterogeneity in the vDG. Exposure to an anxiogenic environment recruited vDG neurons with the most transcriptional impact. Differentially expressed synapse-relevant genes in ensemble neurons tended to be differentially methylated. Finally, this ensemble exhibited higher activity in threatening than safe environment suggesting a prenatal adversity-induced epigenetic and neurobiological sequalae that leads to anxiety.
2025-07-31 | GSE284416 | GEO