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Eur Neuropsychopharmacol. 2018 Mar;28(3):401-414. doi: 10.1016/j.euroneuro.2017.12.015. Epub 2017 Dec 27.

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

Author information

1
APHM, Department of psychiatry, Marseille, France; Aix Marseille Univ, CNRS, CRN2M, UMR 7286, Marseille, France; Fondation FondaMental, Fondation de Recherche et de Soins en Santé Mentale, Créteil, France.
2
Aix Marseille Univ, CNRS, CRN2M, UMR 7286, Marseille, France; Fondation FondaMental, Fondation de Recherche et de Soins en Santé Mentale, Créteil, France; Aix Marseille Univ, CNRS, INT, Inst Neurosci Timone, Marseille, France.
3
CIC-CPCET, APHM, Hôpital La Timone, Marseille, France.
4
APHM, Department of psychiatry, Marseille, France; Aix Marseille Univ, SPMC, EA 3279, Public Health, Chronic Diseases and Quality of Life - Research Unit, Marseille, France.
5
Fondation FondaMental, Fondation de Recherche et de Soins en Santé Mentale, Créteil, France; Department of Emergency Psychiatry and Acute Care, CHU Montpellier, France; Inserm, U1061, University of Montpellier, Montpellier, France.
6
Aix Marseille Univ, CNRS, INT, Inst Neurosci Timone, Marseille, France.
7
CHRU de Tours, Clinique Psychiatrique Universitaire, Tours, France; Inserm U1253 Imaging & Brain, Université de Tours, Tours, France.
8
Fondation FondaMental, Fondation de Recherche et de Soins en Santé Mentale, Créteil, France; CHU Clermont-Ferrand, Department of Psychiatry, EA 7280, University of Clermont Auvergne, Clermont-Ferrand, France.
9
Department of Adult Psychiatry, CHRU Nimes, Nimes, France.
10
Inserm, U1061, University of Montpellier, Montpellier, France; Department of Adult Psychiatry, CHRU Nimes, Nimes, France.
11
Fondation FondaMental, Fondation de Recherche et de Soins en Santé Mentale, Créteil, France; Department of Clinical Psychiatry, University Hospital, Besançon, France; EA 481, Laboratory of Neurosciences, University of Franche-Comté, Besançon, France; CIC-1431 Inserm, University Hospital, Besançon, France.
12
Aix Marseille Univ, SPMC, EA 3279, Public Health, Chronic Diseases and Quality of Life - Research Unit, Marseille, France.
13
APHM, Department of psychiatry, Marseille, France.
14
APHM, Department of psychiatry, Marseille, France; Fondation FondaMental, Fondation de Recherche et de Soins en Santé Mentale, Créteil, France; Aix Marseille Univ, CNRS, INT, Inst Neurosci Timone, Marseille, France.
15
CHRU de Tours, Clinique Psychiatrique Universitaire, Tours, France; Inserm U1253 Imaging & Brain, Université de Tours, Tours, France; Inserm CIC 1415, Centre d'Investigation Clinique, CHRU de Tours, Tours, France.
16
APHM, Department of psychiatry, Marseille, France; Aix Marseille Univ, CNRS, CRN2M, UMR 7286, Marseille, France; Fondation FondaMental, Fondation de Recherche et de Soins en Santé Mentale, Créteil, France; McGill Group for Suicide Studies, Department of Psychiatry, McGill University, Douglas Mental Health University Institute, Montreal, QC, Canada. Electronic address: raoul.belzeaux@ap-hm.fr.

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 2nd 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 2nd and 8th 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

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