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

Authors Firouzabadi N, Navabzadeh N, Moghimi-Sarani E, Haghnegahdar M

Received 19 February 2020

Accepted for publication 22 April 2020

Published 4 May 2020 Volume 2020:16 Pages 1121—1128


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Roger Pinder

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, Iran

Correspondence: Negar Firouzabadi
Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
Tel +98 917-314-5303
Fax +98 713-2424128
Email [email protected]

Background: 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

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