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J Affect Disord. 2018 Nov;240:230-236. doi: 10.1016/j.jad.2018.07.062. Epub 2018 Jul 24.

Glycogen synthase kinase-3β genetic polymorphisms and insomnia in depressed patients: A prospective study.

Author information

1
CESP/UMR-S1178, Equipe "Dépression et Antidépresseurs", Univ Paris-Sud, Faculté de Médecine, INSERM, Le Kremlin Bicêtre, France; Service Hospitalo-Universitaire de Psychiatrie de Bicêtre, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris, Le Kremlin Bicêtre, France; Dispositif Territorial de Recherche et Formation (DTRF) Paris Sud.
2
CESP/UMR-S1178, Equipe "Dépression et Antidépresseurs", Univ Paris-Sud, Faculté de Médecine, INSERM, Le Kremlin Bicêtre, France; Service Hospitalo-Universitaire de Psychiatrie de Bicêtre, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris, Le Kremlin Bicêtre, France.
3
CESP/UMR-S1178, Equipe "Dépression et Antidépresseurs", Univ Paris-Sud, Faculté de Médecine, INSERM, Le Kremlin Bicêtre, France.
4
Sorbonne Universities, Pierre and Marie Curie University Paris 6, INSERM, Saint-Antoine Research Center, Saint-Antoine Hospital; Hospitalo-Universitary Institute, ICAN; Department of Endocrinology, Saint-Antoine Hospital, Assistance Publique-Hôpitaux de Paris, Paris France; INSERM, UMR S_938- Centre de Recherche Saint-Antoine, Paris, France.
5
CESP/UMR-S1178, Equipe "Dépression et Antidépresseurs", Univ Paris-Sud, Faculté de Médecine, INSERM, Le Kremlin Bicêtre, France; Service de Génétique Moléculaire, pharmacogénétique et hormonologie, Assistance Publique-Hôpitaux de Paris, Le Kremlin Bicêtre, France.
6
Service de Génétique Moléculaire, pharmacogénétique et hormonologie, Assistance Publique-Hôpitaux de Paris, Le Kremlin Bicêtre, France.
7
UPMC Paris 6; Department of Psychiatry, Saint-Antoine Hospital, Paris, France.
8
Department of Clinical Psychiatry, University Hospital; EA 481, Laboratory of Neurosciences, University of Bourgogne Franche-Comté; CIC-1431 Inserm, University Hospital, Besançon, France.
9
Univ. Grenoble Alpes; Inserm U1216, Grenoble Institut de Neurosciences, CHU de Grenoble, F-38000 Grenoble, France.
10
CESP/UMR-S1178, Equipe "Dépression et Antidépresseurs", Univ Paris-Sud, Faculté de Médecine, INSERM, Le Kremlin Bicêtre, France; Centre de Recherche Clinique Paris Sud, Assistance Publique-Hôpitaux de Paris, Le Kremlin Bicêtre, France.
11
CESP/UMR-S1178, Equipe "Dépression et Antidépresseurs", Univ Paris-Sud, Faculté de Médecine, INSERM, Le Kremlin Bicêtre, France; Service Hospitalo-Universitaire de Psychiatrie de Bicêtre, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris, Le Kremlin Bicêtre, France; Dispositif Territorial de Recherche et Formation (DTRF) Paris Sud. Electronic address: emmanuelle.corruble@aphp.fr.

Abstract

BACKGROUND:

80-90% of patients with Major Depressive Episode (MDE) experience insomnia and up-to 50% severe insomnia. Glycogen Synthase Kinase-3β (GSK3B) is involved both in mood regulation and circadian rhythm. Since GSK3B polymorphisms could affect protein levels or functionality, we investigated the association of GSK3B polymorphisms with insomnia in a sample of depressed patients treated with antidepressants.

METHODS:

In this 6-month prospective real-world treatment study in psychiatric settings (METADAP), 492 Caucasian patients requiring a new antidepressant treatment were included and genotyped for five GSK3B Single Nucleotide Polymorphisms (SNPs) (rs6808874, rs6782799, rs2319398, rs13321783, rs334558). Insomnia and MDE severity were rated using the Hamilton Depression Rating Scale (HDRS). Bi- and multivariate analyses were performed to assess the association between GSK3B SNPs and insomnia (main objective). We also assessed their association with MDE severity and HDRS response/remission after antidepressant treatment.

RESULTS:

At baseline severe insomnia was associated with the GSK3B rs334558 minor allele (C+) [OR=1.81, CI95%(1.17-2.80), p=0.008]. GSK3B rs334558 C+ had greater insomnia improvement after 6 months of antidepressant treatment (p=0.007, β=0.17, t=2.736). No association was found between GSK3B SNPs and MDE baseline severity or 6-month response/remission.

CONCLUSION:

GSK3B rs334558 was associated with insomnia but not with MDE severity in depressed patients. Targeting GSK3B in patients with MDE and a severe insomnia could be a way to improve their symptoms with greater efficiency. And it should be further studied whether the GSK3B-insomnia association may fit into the larger picture of mood disorders.

KEYWORDS:

Antidepressants response; GSK3B; Insomnia; MDD; MDE; Single nucleotide polymorphism

PMID:
30081294
DOI:
10.1016/j.jad.2018.07.062
[Indexed for MEDLINE]

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