Serotonin transporter gene expression predicts the worsening of suicidal ideation and suicide attempts along a long-term follow-up of a Major Depressive Episode

Abstract

The quest for biomarkers in suicidal behaviors has been elusive so far, despite their potential utility in clinical practice. One of the most robust biological findings in suicidal behaviors is the alteration of the serotonin transporter function in suicidal individuals. Our main objective was to investigate the predictive value of the serotonin transporter gene expression (SLC6A4) for suicidal ideation and as secondary, for suicide attempts in individuals with a major depressive episode (MDE). A 30-week prospective study was conducted on 148 patients with a MDE and 100 healthy controls including 4 evaluation times (0, 2, 8 and 30 weeks). Blood samples and clinical data were collected and SLC6A4 mRNA levels were measured from peripheral blood mononuclear cells using RT-qPCR. We first demonstrated the stability and reproducibility of SLC6A4 mRNA expression measures over time in healthy controls (F=0.658; p=0.579; η²=0.008; ICC=0.91, 95% CI [0.87-0.94]). Baseline SLC6A4 expression level (OR=0.563 [0.340-0.932], p=0.026) as well as early changes in SLC6A4 expression between baseline and the 2^nd week (β=0.200, p=0.042) predicted the worsening of suicidal ideation (WSI) in the following 8 weeks. Moreover, changes in SLC6A4 expression between the 2^nd and 8^th weeks predicted the occurrence of a suicide attempt within 30 weeks (OR=10.976 [1.438-83.768], p=0.021). Altogether, the baseline level and the changes in SLC6A4 mRNA expression during a MDE might predict the WSI and the occurrence of suicidal attempts and could be a useful biomarker in clinical practice.

Keywords: Gene expression; Major depression; Serotonin transporter; Suicide; biomarker.