B. Nobile, 1, N. Ramoz, 2, I. Jaussent, 3, Ph Gorwood, 2, E. Olié, 1, 3, 4, J. Lopez Castroman, 3, 5
S. Guillaume 1, 3, 4, Ph Courtet 1, 3, 4
1 Department of Emergency Psychiatry and Post-Acute Care, CHU Montpellier, Montpellier, France
2 INSERM UMRS1266, Institute of Psychiatry and Neuroscience of Paris, Université Sorbonne Paris Cité, Paris, France
3 INSERM, U1061, Neuropsychiatry, University Montpellier, Montpellier, France
4 FondaMental Foundation, Montpellier, France
5 Department of Psychiatry, CHU Nimes, Nimes, France
Scientific Reports volume 9, Article number: 2569 (2019)
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Abstract
Antidepressants
have been the object of an international controversy for about thirty
years. Some patients are inclined to develop suicidal ideation (SI) at
antidepressant onset; this phenomenon is known as Treatment Emergent
Suicidal Ideation (TESI), and it has conducted regulatory bodies to
prompt warnings on antidepressants. Since, few studies have explored the
pharmacogenomics of TESI. Given the growing body of evidence connecting
the opioidergic system with suicidal behavior (particularly mu opioid
receptor (MOR)), we decided to examine the relationship between two
genetic polymorphisms (SNPs) in the opioidergic system and TESI in a
sample of 3566 adult depressed outpatients. General practitioners and
psychiatrists throughout France followed participants for 6 weeks after
an initial prescription of tianeptine, an antidepressant treatment with
mu agonism. Suicidal ideation was assessed with the item 10 of the
Montgomery-Asberg Depression Rating Scale (item dedicated to SI) at
baseline, and after 2 weeks, 4 weeks and 6 weeks. We analysed rs1799971
from the OPRM1 gene and rs105660 from the OPRK1 gene.
Within the sample, 112 patients reported TESI while 384 did not. We
found a significant association between AA genotype of rs1799971 and
TESI even after adjustment for potential cofounders (OR = 1.93, 95%
CI = [1.07; 3.49]; p-value = 0.03). On the other hand there were
no significant association between rs1799971 and rs105560 with worsening
of suicidal ideation or lifetime suicide attempts. Nevertheless, our
results suggest a possible involvement of opioidergic system in TESI.
https://www.nature.com/articles/s41598-019-39622-3#Bib1
https://www.nature.com/articles/s41598-019-39622-3#Bib1
