Association of SLC6A4 methylation with early adversity, characteristics and outcomes in depression

Childhood adversities have been associated with onset and worse clinical presentations of depression. Epigenetic changes may reflect childhood adversities, while their effects on clinical characteristics of depression are unknown. This study aimed to investigate whether epigenetic changes were associated with childhood adversities, pretreatment characteristics, and treatment outcomes in depressive patients. In 108 patients with major depressive disorders, the methylation status in the promoter of gene encoding serotonin transporter (SLC6A4) was measured. Childhood adversities, socio-demographic and clinical characteristics including assessment scales for depression (Hamilton Depression Rating Scale, HAMD), anxiety (Hamilton Anxiety Rating Scale, HAMA), functioning (Social and Occupational Functioning Assessment Scale, SOFAS), disability (World Health Organization Disability Assessment Schedule-12, WHODAS-12), and quality of life (World Health Organization Quality of Life-Abbreviated form, WHOQOL-BREF) were evaluated at baseline. After a 12-week treatment with antidepressants, the assessment scales were reevaluated. To avoid type I error by multiple comparisons, Bonferroni corrections were applied. Higher SLC6A4 promoter methylation status was significantly associated with childhood adversities, worse clinical presentation (family history of depression, higher perceived stress, and more severe psychopathology assessed by SOFAS, WHODAS-12, and WHOQOL-BREF), but was not associated with treatment outcomes after considering multiple comparisons. SLC6A4 methylation status could be a proxy marker for childhood adversities and a clinical biomarker for certain presentations of depression. ► SLC6A4 methylation was associated with childhood adversity in depressive patients. ► SLC6A4 methylation was associated with more severe depression at presentation. ► Associations of SLC6A4 methylation with treatment outcomes are yet to be determined. ► SLC6A4 methylation could be a biomarker for certain presentations of depression.