The relationship of methylation and mRNA expression profile of AUTS2 with suicidal ideation in adolescents with bipolar depression

Abstract Objective This study aims to explore the correlation between the methylation levels of the AUTS2 gene and suicidal ideation in adolescents with bipolar depression, and investigate the mediating effect of AUTS2 mRNA expression levels. Methods A total of 73 adolescents diagnosed with bipolar...

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Main Authors: Xiaoqin Shen, Chengji Wang, Alimire Alimujiang, Cheng Zhang, Shaohong Zou, Lu Liu
Format: Article
Language:English
Published: BMC 2025-05-01
Series:BMC Psychiatry
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Online Access:https://doi.org/10.1186/s12888-025-06927-9
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Summary:Abstract Objective This study aims to explore the correlation between the methylation levels of the AUTS2 gene and suicidal ideation in adolescents with bipolar depression, and investigate the mediating effect of AUTS2 mRNA expression levels. Methods A total of 73 adolescents diagnosed with bipolar depression were recruited for the evaluation of suicidal ideation using the Suicidal Ideation Attributes Scale (SIOSS) and were categorized into two groups (with or without suicidal ideation). The methylation and mRNA expression levels of the AUTS2 gene were detected through pyrophosphate sequencing and quantitative reverse transcription polymerase chain reaction (qRT-PCR) respectively, and were analyzed for the association with suicidal ideation by group comparison, correlation analyses and mediation analyses. Results Among 17 methylation sites identified, the methylation levels at the CpG14.15.16 loci were elevated in the group with suicidal ideation compared to those without such thoughts. The mRNA expression level of AUTS2 was also found be higher in the group with suicidal ideation. Quantitative analyses indicated significant correlation between the methylation level and suicidal ideation, between the methylation level of CpG14.15.16 loci and AUTS2 expression, and between its expression level and suicidal ideation. Further mediation analyses indicated that the AUTS2 mRNA expression levels mediated the relationship between the methylation levels at CpG14.15.16 and suicidal ideation, accounting for 30% of the observed effect. Conclusion The elevated methylation level of CpG14.15.16 of the AUTS2 gene might be involved in the pathophysiology of suicide ideation in adolescents with bipolar depression, which might be mediated by the mRNA expression of AUTS2.
ISSN:1471-244X