Orexin/Hypocretin Type 2 Receptor (HCRTR2) Gene as a Candidate Gene in Sertraline-Associated Insomnia in Depressed Patients

Negar Firouzabadi,1,2 Niloofar Navabzadeh,1 Ebrahim Moghimi-Sarani,3 Maral Haghnegahdar1 1Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran; 2Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran;...

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Autores principales:	Firouzabadi N, Navabzadeh N, Moghimi-Sarani E, Haghnegahdar M
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	orexin receptor-2 sleep insomnia selective serotonin reuptake inhibitors sertraline Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/480122a92ed24f73a3287c26258002f4
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spelling	oai:doaj.org-article:480122a92ed24f73a3287c26258002f42021-12-02T10:38:57ZOrexin/Hypocretin Type 2 Receptor (HCRTR2) Gene as a Candidate Gene in Sertraline-Associated Insomnia in Depressed Patients1178-2021https://doaj.org/article/480122a92ed24f73a3287c26258002f42020-05-01T00:00:00Zhttps://www.dovepress.com/orexinhypocretin-type-2-receptor-hcrtr2-gene-as-a-candidate-gene-in-se-peer-reviewed-article-NDThttps://doaj.org/toc/1178-2021Negar Firouzabadi,1,2 Niloofar Navabzadeh,1 Ebrahim Moghimi-Sarani,3 Maral Haghnegahdar1 1Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran; 2Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; 3Department of Psychiatry, School of Medicine, Shiraz University of Medical Sciences, School of Medicine, Shiraz, IranCorrespondence: Negar FirouzabadiDepartment of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, IranTel +98 917-314-5303Fax +98 713-2424128Email nfirouzabadi@yahoo.comBackground: Selective serotonin reuptake inhibitors (SSRIs) are considered as ﬁrst-line drugs for treating depressive disorders. Among the adverse effects reported with sertraline is sleep disturbances; however, the etiology lying beneath is obscure. Orexin, the most recently discovered neurotransmitter, is involved in the sleep cycle. It exerts its physiological actions through orexin or hypocretin type 1 and 2 receptors (HCRTR1 and HCRTR2). Dysfunction of the orexin system contributes to various psychiatric, neurologic and neuropsychiatric disorders. Thus, our study aimed to assess the possible association of genetic variation of HCRTR2 G1246A with hypersomnia reported with sertraline in a group of major depressive disorder (MDD) patients.Patients and Methods: Ninety-six newly diagnosed MDD patients were enrolled in our cohort study. MDD was assessed using DSM-V criteria. Insomnia Severity Index (ISI) was used to assess insomnia at baseline (week 0) and week 4. Blood samples were collected for further genotyping of HCRTR2 G1246A (rs2653349) using polymerase chain reaction-restriction fragment length polymorphism.Results: A significant association between G1264A polymorphism of HCRTR2 and insomnia was observed. Insomnia with sertraline happens by 2.5-fold (P=0.022; odds ratio (OR)=2.5; 95% confidence interval (CI): 1.1– 5.7) in patients having GG genotype. Patients with G allele experience insomnia by 2.1-fold more than A allele carriers (P=0.022; OR=2.1; 95% CI= 1.1– 4.0). Subgroup analysis showed a significant association between GG genotype as well as the G allele and insomnia only in female MDD patients (P=0.011; OR=4.0; 95% CI=1.3– 12.0 and P=0.033; OR=2.4; 95% CI=1.02– 5.7, respectively).Conclusion: In conclusion, the G1246A variant might be a predictor for insomnia in MDD patients treated with sertraline. Our findings support the idea that some variants of the HCRTR might contribute to inter-individual variability in the sleep pattern of patients receiving antidepressants.Keywords: orexin receptor 2, sleep, insomnia, selective serotonin reuptake inhibitors, sertralineFirouzabadi NNavabzadeh NMoghimi-Sarani EHaghnegahdar MDove Medical Pressarticleorexin receptor-2sleepinsomniaselective serotonin reuptake inhibitorssertralineNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol Volume 16, Pp 1121-1128 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	orexin receptor-2 sleep insomnia selective serotonin reuptake inhibitors sertraline Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
spellingShingle	orexin receptor-2 sleep insomnia selective serotonin reuptake inhibitors sertraline Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Firouzabadi N Navabzadeh N Moghimi-Sarani E Haghnegahdar M Orexin/Hypocretin Type 2 Receptor (HCRTR2) Gene as a Candidate Gene in Sertraline-Associated Insomnia in Depressed Patients
description	Negar Firouzabadi,1,2 Niloofar Navabzadeh,1 Ebrahim Moghimi-Sarani,3 Maral Haghnegahdar1 1Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran; 2Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; 3Department of Psychiatry, School of Medicine, Shiraz University of Medical Sciences, School of Medicine, Shiraz, IranCorrespondence: Negar FirouzabadiDepartment of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, IranTel +98 917-314-5303Fax +98 713-2424128Email nfirouzabadi@yahoo.comBackground: Selective serotonin reuptake inhibitors (SSRIs) are considered as ﬁrst-line drugs for treating depressive disorders. Among the adverse effects reported with sertraline is sleep disturbances; however, the etiology lying beneath is obscure. Orexin, the most recently discovered neurotransmitter, is involved in the sleep cycle. It exerts its physiological actions through orexin or hypocretin type 1 and 2 receptors (HCRTR1 and HCRTR2). Dysfunction of the orexin system contributes to various psychiatric, neurologic and neuropsychiatric disorders. Thus, our study aimed to assess the possible association of genetic variation of HCRTR2 G1246A with hypersomnia reported with sertraline in a group of major depressive disorder (MDD) patients.Patients and Methods: Ninety-six newly diagnosed MDD patients were enrolled in our cohort study. MDD was assessed using DSM-V criteria. Insomnia Severity Index (ISI) was used to assess insomnia at baseline (week 0) and week 4. Blood samples were collected for further genotyping of HCRTR2 G1246A (rs2653349) using polymerase chain reaction-restriction fragment length polymorphism.Results: A significant association between G1264A polymorphism of HCRTR2 and insomnia was observed. Insomnia with sertraline happens by 2.5-fold (P=0.022; odds ratio (OR)=2.5; 95% confidence interval (CI): 1.1– 5.7) in patients having GG genotype. Patients with G allele experience insomnia by 2.1-fold more than A allele carriers (P=0.022; OR=2.1; 95% CI= 1.1– 4.0). Subgroup analysis showed a significant association between GG genotype as well as the G allele and insomnia only in female MDD patients (P=0.011; OR=4.0; 95% CI=1.3– 12.0 and P=0.033; OR=2.4; 95% CI=1.02– 5.7, respectively).Conclusion: In conclusion, the G1246A variant might be a predictor for insomnia in MDD patients treated with sertraline. Our findings support the idea that some variants of the HCRTR might contribute to inter-individual variability in the sleep pattern of patients receiving antidepressants.Keywords: orexin receptor 2, sleep, insomnia, selective serotonin reuptake inhibitors, sertraline
format	article
author	Firouzabadi N Navabzadeh N Moghimi-Sarani E Haghnegahdar M
author_facet	Firouzabadi N Navabzadeh N Moghimi-Sarani E Haghnegahdar M
author_sort	Firouzabadi N
title	Orexin/Hypocretin Type 2 Receptor (HCRTR2) Gene as a Candidate Gene in Sertraline-Associated Insomnia in Depressed Patients
title_short	Orexin/Hypocretin Type 2 Receptor (HCRTR2) Gene as a Candidate Gene in Sertraline-Associated Insomnia in Depressed Patients
title_full	Orexin/Hypocretin Type 2 Receptor (HCRTR2) Gene as a Candidate Gene in Sertraline-Associated Insomnia in Depressed Patients
title_fullStr	Orexin/Hypocretin Type 2 Receptor (HCRTR2) Gene as a Candidate Gene in Sertraline-Associated Insomnia in Depressed Patients
title_full_unstemmed	Orexin/Hypocretin Type 2 Receptor (HCRTR2) Gene as a Candidate Gene in Sertraline-Associated Insomnia in Depressed Patients
title_sort	orexin/hypocretin type 2 receptor (hcrtr2) gene as a candidate gene in sertraline-associated insomnia in depressed patients
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/480122a92ed24f73a3287c26258002f4
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Orexin/Hypocretin Type 2 Receptor (HCRTR2) Gene as a Candidate Gene in Sertraline-Associated Insomnia in Depressed Patients

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