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Decreased telomere length in a subgroup of young individuals with bipolar disorders: replication in the FACE-BD cohort and association with the shelterin component POT1

Published online by Cambridge University Press:  27 August 2024

L. Spano ,
C. Marie-Claire ,
O. Godin ,
M. Leboyer ,
B. Aouizerate ,
A. Lefrere ,
R. Belzeaux ,
P. Courtet ,
E. Olie  and
C. Dubertret
...Show all authors
L. Spano*
Affiliation:
1Université Paris Cité, INSERM UMR-S 1144, Optimisation Thérapeutique en Neuropsychopharmacologie OTeN, Paris
C. Marie-Claire
Affiliation:
1Université Paris Cité, INSERM UMR-S 1144, Optimisation Thérapeutique en Neuropsychopharmacologie OTeN, Paris
O. Godin
Affiliation:
2Fondation FondaMental 3Université Paris Est Créteil, INSERM U955, IMRB, Translational NeuroPsychiatry Laboratory
M. Leboyer
Affiliation:
2Fondation FondaMental 3Université Paris Est Créteil, INSERM U955, IMRB, Translational NeuroPsychiatry Laboratory 4AP-HP, Hôpitaux Universitaires Henri Mondor, Département Médico-Universitaire de Psychiatrie et d’Addictologie (DMUIMPACT), Fédération Hospitalo-Universitaire de Médecine de Précision en Psychiatrie (FHU ADAPT), Créteil
B. Aouizerate
Affiliation:
2Fondation FondaMental 5Centre Hospitalier Charles Perrens, Laboratoire NutriNeuro (UMR INRA 1286), Université de Bordeaux, Bordeaux
A. Lefrere
Affiliation:
2Fondation FondaMental 6Pôle de Psychiatrie, Assistance Publique Hôpitaux de Marseille
R. Belzeaux
Affiliation:
2Fondation FondaMental 7INT-UMR7289, CNRS Aix-Marseille Université, Marseille 8Université Montpellier, Montpellier
P. Courtet
Affiliation:
2Fondation FondaMental 9Department of Emergency Psychiatry and Acute Care, CHU Montpellier, IGF, Univ. Montpellier, CNRS, INSERM, Créteil
E. Olie
Affiliation:
2Fondation FondaMental 10Department of Emergency Psychiatry and Acute Care, CHU Montpellier, IGF, Univ. Montpellier, CNRS, INSERM, Montpellier
C. Dubertret
Affiliation:
2Fondation FondaMental 11AP-HP, Groupe Hospitalo-Universitaire AP-HP Nord, DMU ESPRIT, Service de Psychiatrie et Addictologie, Hôpital Louis Mourier, Colombes 12Université de Paris, Inserm UMR1266, Sorbonne Paris Cité, Faculté de Médecine, Paris
R. Schwan
Affiliation:
2Fondation FondaMental 13Université de Lorraine, Centre Psychothérapique de Nancy, Inserm U1254, Nancy
V. Aubin
Affiliation:
2Fondation FondaMental 14Pôle de Psychiatrie, Centre Hospitalier Princesse Grace, Monaco
P. Roux
Affiliation:
2Fondation FondaMental 15Centre Hospitalier de Versailles, Service Universitaire de Psychiatrie d’Adulte et d’Addictologie, Le Chesnay 16Equipe DisAP-PsyDev, CESP, Université Versailles Saint- Quentin-en-Yvelines – Paris-Saclay , Inserm, Villejuif
M. Polosan
Affiliation:
2Fondation FondaMental 17Université Grenoble Alpes, Inserm, U1216, CHU Grenoble Alpes, Grenoble Institut Neurosciences, Grenoble
L. Samalin
Affiliation:
2Fondation FondaMental 18Centre Hospitalier et Universitaire, Département de Psychiatrie, Université Clermont Auvergne, CNRS, Clermont Auvergne INP, Institut Pascal (UMR 6602), Clermont-Ferrand
E. Haffen
Affiliation:
2Fondation FondaMental 19Service de Psychiatrie de l’Adultre, CIC-1431 INSERM, CHU de Besançon, Laboratoire de Neurosciences, UFC, UBFC, Besançon
F. Bellivier
Affiliation:
1Université Paris Cité, INSERM UMR-S 1144, Optimisation Thérapeutique en Neuropsychopharmacologie OTeN, Paris 2Fondation FondaMental 20AP-HP, Groupe Hospitalo-Universitaire AP-HP Nord, DMU Neurosciences, Hôpital Fernand Widal, Département de Psychiatrie et de Médecine Addictologique, Paris, France
B. Etain
Affiliation:
1Université Paris Cité, INSERM UMR-S 1144, Optimisation Thérapeutique en Neuropsychopharmacologie OTeN, Paris 2Fondation FondaMental 20AP-HP, Groupe Hospitalo-Universitaire AP-HP Nord, DMU Neurosciences, Hôpital Fernand Widal, Département de Psychiatrie et de Médecine Addictologique, Paris, France
*
*Corresponding author.

Abstract

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Introduction

A 10-15 years decrease in life expectancy has been observed in individuals with bipolar disorder (BD) and has been associated with premature cellular aging, but mechanisms involved remain unclear. Our team recently identified a subgroup of young individuals with prematurely shortened telomere length (TL).

Objectives

The aims of the present study were to replicate this observation in a larger sample and to analyze the expression levels of genes associated with age or TL in a subsample of these individuals.

Methods

TL was measured by qPCR using peripheral blood DNA from 542 individuals with BD. Clustering analyzes were performed with age and TL as classification variables to identify similar groups.

Gene expression of 29 genes, including 20 associated with age and 9 with TL, was analyzed by RT-qPCR using peripheral blood RNA in a subgroup of 129 individuals. Gene expressions were compared between groups obtained from the previous clustering analyzes by Kruskal-Wallis and Mann-Whitney tests.

Results

Clustering analyzes identified 3 subgroups and replicated the clustering previously described: a subgroup of aged individuals with a low TL (mean age : 51.73 years ; mean TL : 2), a subgroup of young individuals with a high TL (mean age : 29.02 years ; mean TL : 4.36) and a subgroup of young individuals but with a low TL (mean age : 29.64 years ; mean TL : 1.96). None of the tested clinical variables were significantly associated with this subgroup.

Furthermore, gene expression level analyzes showed that only POT1 expression was different between the two subgroups of young individuals, with a downregulation of POT1 expression in the subgroup with a lower TL level. POT1 is a protein involved in the maintenance of TL. POT1 binds to another protein TPP1 allowing the recruitment of telomerase, the enzyme which extends TL. Our hypothesis is that in the subgroup presenting a lower POT1 expression, the POT1-TPP1 complex cannot form and thus prevents telomerase recruitment and TL elongation.

Conclusions

This study confirms, on a larger sample, the existence of a subgroup of young individuals with BD presenting accelerated cellular aging. The observed decrease of POT1 expression level suggests a newly described cellular mechanism in individuals with BD, that may contribute to telomere shortening.

Disclosure of Interest

None Declared

Type
Abstract
Information
European Psychiatry , Volume 67 , Special Issue S1: Abstracts of the 32nd European Congress of Psychiatry , April 2024 , pp. S219
Creative Commons
Creative Common License - CCCreative Common License - BY
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Copyright
© The Author(s), 2024. Published by Cambridge University Press on behalf of European Psychiatric Association
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