Association Study of Serotonin 3 Receptor Subunit Gene Variants in Antipsychotic-Induced Weight Gain

Overview

Journal Neuropsychobiology

Specialty Neurology

Date 2017 May 23

PMID 28531893

Citations 3

Authors

Clement C Zai

Arun K Tiwari

Nabilah I Chowdhury

Eva J Brandl

Sajid A Shaikh

Natalie Freeman

Jeffrey A Lieberman

Herbert Y Meltzer

James L Kennedy

Daniel J Muller

Affiliations

Soon will be listed here.

Abstract

Background: Schizophrenia (SCZ) is a chronic severe neuropsychiatric disorder, where pharmacological treatment has been hindered by adverse effects, including antipsychotic-induced weight gain (AIWG) and related complications. Genetic studies have been exploring the appetite regulation and energy homeostasis pathways in AIWG with some promising leads. The serotonin system has been shown to participate in these pathways.

Methods: In the current study, we examined single nucleotide polymorphisms across the serotonin receptor genes HTR3A and HTR3B. Prospective weight change was assessed for a total of 149 SCZ patients of European ancestry.

Results: We did not find the tested HTR3A or HTR3B gene markers to be associated with AIWG in our sample.

Conclusion: Our preliminary findings suggest that these receptors may not play a major role in predicting AIWG.

Citing Articles

Genetic Polymorphisms of Receptors and Antipsychotic-Induced Metabolic Dysfunction in Patients with Schizophrenia.

Paderina D, Boiko A, Pozhidaev I, Bocharova A, Mednova I, Fedorenko O J Pers Med. 2021; 11(3).

PMID: 33807811 PMC: 7999828. DOI: 10.3390/jpm11030181.

Pharmacogenetics of Antipsychotic Drug Treatment: Update and Clinical Implications.

Yoshida K, Muller D Mol Neuropsychiatry. 2020; 5(Suppl 1):1-26.

PMID: 32399466 PMC: 7206586. DOI: 10.1159/000492332.

Intrinsic and Antipsychotic Drug-Induced Metabolic Dysfunction in Schizophrenia.

Freyberg Z, Aslanoglou D, Shah R, Ballon J Front Neurosci. 2017; 11:432.

PMID: 28804444 PMC: 5532378. DOI: 10.3389/fnins.2017.00432.

References

Endicott J . Good diagnoses require good diagnosticians: collecting and integrating the data. Am J Med Genet. 2001; 105(1):48-9. View

Creta E, Fabbri C, Serretti A . Genetics of second-generation antipsychotic and mood stabilizer-induced weight gain in bipolar disorder: common and specific effects of key regulators of fat-mass homoeostasis genes. Pharmacogenet Genomics. 2015; 25(7):354-62. DOI: 10.1097/FPC.0000000000000144. View

Masellis M, Basile V, Meltzer H, Lieberman J, Sevy S, Macciardi F . Serotonin subtype 2 receptor genes and clinical response to clozapine in schizophrenia patients. Neuropsychopharmacology. 1998; 19(2):123-32. DOI: 10.1016/S0893-133X(98)00007-4. View

Hayes M, Covasa M . CCK and 5-HT act synergistically to suppress food intake through simultaneous activation of CCK-1 and 5-HT3 receptors. Peptides. 2005; 26(11):2322-30. DOI: 10.1016/j.peptides.2005.03.045. View

Oh C, Namkung J, Go Y, Shong K, Kim K, Kim H . Regulation of systemic energy homeostasis by serotonin in adipose tissues. Nat Commun. 2015; 6:6794. PMC: 4403443. DOI: 10.1038/ncomms7794. View

Weber S, Volynets V, Kanuri G, Bergheim I, Bischoff S . Treatment with the 5-HT3 antagonist tropisetron modulates glucose-induced obesity in mice. Int J Obes (Lond). 2009; 33(12):1339-47. DOI: 10.1038/ijo.2009.191. View

Nurmi E, Spilman S, Whelan F, Scahill L, Aman M, McDougle C . Moderation of antipsychotic-induced weight gain by energy balance gene variants in the RUPP autism network risperidone studies. Transl Psychiatry. 2013; 3:e274. PMC: 3693401. DOI: 10.1038/tp.2013.26. View

Rammes G, Eisensamer B, Ferrari U, Shapa M, Gimpl G, Gilling K . Antipsychotic drugs antagonize human serotonin type 3 receptor currents in a noncompetitive manner. Mol Psychiatry. 2004; 9(9):846-58, 818. DOI: 10.1038/sj.mp.4001490. View

Malhotra A, Correll C, Chowdhury N, Muller D, Gregersen P, Lee A . Association between common variants near the melanocortin 4 receptor gene and severe antipsychotic drug-induced weight gain. Arch Gen Psychiatry. 2012; 69(9):904-12. PMC: 4166499. DOI: 10.1001/archgenpsychiatry.2012.191. View

10.

Dudbridge F . Likelihood-based association analysis for nuclear families and unrelated subjects with missing genotype data. Hum Hered. 2008; 66(2):87-98. PMC: 2386559. DOI: 10.1159/000119108. View

11.

Strange P . Antipsychotic drugs: importance of dopamine receptors for mechanisms of therapeutic actions and side effects. Pharmacol Rev. 2001; 53(1):119-33. View

12.

Ohara-Imaizumi M, Kim H, Yoshida M, Fujiwara T, Aoyagi K, Toyofuku Y . Serotonin regulates glucose-stimulated insulin secretion from pancreatic β cells during pregnancy. Proc Natl Acad Sci U S A. 2013; 110(48):19420-5. PMC: 3845121. DOI: 10.1073/pnas.1310953110. View

13.

Arranz M, De Leon J . Pharmacogenetics and pharmacogenomics of schizophrenia: a review of last decade of research. Mol Psychiatry. 2007; 12(8):707-47. DOI: 10.1038/sj.mp.4002009. View

14.

Li J, Ji L . Adjusting multiple testing in multilocus analyses using the eigenvalues of a correlation matrix. Heredity (Edinb). 2005; 95(3):221-7. DOI: 10.1038/sj.hdy.6800717. View

15.

Muller D, Zai C, Sicard M, Remington E, Souza R, Tiwari A . Systematic analysis of dopamine receptor genes (DRD1-DRD5) in antipsychotic-induced weight gain. Pharmacogenomics J. 2010; 12(2):156-64. DOI: 10.1038/tpj.2010.65. View

16.

Vojvoda D, GRIMMELL K, Sernyak M, Mazure C . Monozygotic twins concordant for response to clozapine. Lancet. 1996; 347(8993):61. DOI: 10.1016/s0140-6736(96)91594-9. View

17.

Barrett J, Fry B, Maller J, Daly M . Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics. 2004; 21(2):263-5. DOI: 10.1093/bioinformatics/bth457. View

18.

Feinle C, Read N . Ondansetron reduces nausea induced by gastroduodenal stimulation without changing gastric motility. Am J Physiol. 1996; 271(4 Pt 1):G591-7. DOI: 10.1152/ajpgi.1996.271.4.G591. View

19.

Volavka J, Czobor P, Sheitman B, Lindenmayer J, Citrome L, McEvoy J . Clozapine, olanzapine, risperidone, and haloperidol in the treatment of patients with chronic schizophrenia and schizoaffective disorder. Am J Psychiatry. 2002; 159(2):255-62. DOI: 10.1176/appi.ajp.159.2.255. View

20.

Lahiri D, Nurnberger Jr J . A rapid non-enzymatic method for the preparation of HMW DNA from blood for RFLP studies. Nucleic Acids Res. 1991; 19(19):5444. PMC: 328920. DOI: 10.1093/nar/19.19.5444. View