Frontiers in psychiatry · 2026
Correlation of non-suicidal self-injury with SLC6A4 promoter DNA methylation in children and adolescents with bipolar depression.
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Alimujiang Alimire, Shen XiaoQin, Wang ChengJi, Zou ShaoHong
Аннотация
PURPOSE: To investigate the association between non-suicidal self-injury (NSSI) and DNA methylation of the SLC6A4 promoter region in individuals diagnosed with bipolar depression.
PATIENTS AND METHODS: A total of 48 children and adolescent patients meeting ICD-10 criteria for bipolar disorder with current depressive episodes (Hamilton Depression Rating Scale-24 score >20) were recruited, and stratified into two groups according to the presence or absence of non-suicidal self-injurious (NSSI) behavior(NSSI group and non-NSSI group). Negative life events were evaluated using the Adolescent Self-Rating Life Events Checklist (ASLEC). The methylation levels of five CpG sites within the SLC6A4 promoter region were determined by pyrosequencing, and mRNA expression was assessed by quantitative reverse transcription polymerase chain reaction (qRT-PCR).
RESULTS: In 48 adolescents with bipolar depression, the two groups were comparable in age, gender, education, only-child status, family history of mental illness, and disease course (all p > 0.05). Compared with the non-NSSI group, the NSSI group showed significantly lower CpG2 methylation at the SLC6A4 promoter, higher SLC6A4 mRNA expression, and higher ASLEC scores. The other four CpG sites showed no significant differences. Spearman's correlation revealed a strong negative association between CpG2 methylation and mRNA expression (ρ = -0.547, p < 0.001). Two logistic regression models both fit the data well. Higher CpG2 methylation was a protective factor against NSSI (OR = 0.131, p = 0.021), while higher mRNA expression was a risk factor (OR = 10.957, p = 0.015). ASLEC scores and interaction terms were not significant.
CONCLUSION: These preliminary findings suggest that lower CpG2 methylation and higher SLC6A4 mRNA expression are each independently associated with NSSI in adolescents with bipolar depression. Stressful life events were higher in the NSSI group, but did not significantly moderate these associations in the current sample. Given the small sample size and cross-sectional design, the results should be viewed as exploratory and require replication in larger studies.
PATIENTS AND METHODS: A total of 48 children and adolescent patients meeting ICD-10 criteria for bipolar disorder with current depressive episodes (Hamilton Depression Rating Scale-24 score >20) were recruited, and stratified into two groups according to the presence or absence of non-suicidal self-injurious (NSSI) behavior(NSSI group and non-NSSI group). Negative life events were evaluated using the Adolescent Self-Rating Life Events Checklist (ASLEC). The methylation levels of five CpG sites within the SLC6A4 promoter region were determined by pyrosequencing, and mRNA expression was assessed by quantitative reverse transcription polymerase chain reaction (qRT-PCR).
RESULTS: In 48 adolescents with bipolar depression, the two groups were comparable in age, gender, education, only-child status, family history of mental illness, and disease course (all p > 0.05). Compared with the non-NSSI group, the NSSI group showed significantly lower CpG2 methylation at the SLC6A4 promoter, higher SLC6A4 mRNA expression, and higher ASLEC scores. The other four CpG sites showed no significant differences. Spearman's correlation revealed a strong negative association between CpG2 methylation and mRNA expression (ρ = -0.547, p < 0.001). Two logistic regression models both fit the data well. Higher CpG2 methylation was a protective factor against NSSI (OR = 0.131, p = 0.021), while higher mRNA expression was a risk factor (OR = 10.957, p = 0.015). ASLEC scores and interaction terms were not significant.
CONCLUSION: These preliminary findings suggest that lower CpG2 methylation and higher SLC6A4 mRNA expression are each independently associated with NSSI in adolescents with bipolar depression. Stressful life events were higher in the NSSI group, but did not significantly moderate these associations in the current sample. Given the small sample size and cross-sectional design, the results should be viewed as exploratory and require replication in larger studies.