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

Zai, Clement C.; Tiwari, Arun K.; Chowdhury, Nabilah I.; Brandl, Eva J.; Shaikh, Sajid; Freeman, Natalie; Lieberman, Jeffrey A.; Meltzer, Herbert Y.; Kennedy, James L.; Müller, Daniel J.

doi:10.1159/000457903

Cited by 4 publications

(2 citation statements)

References 36 publications

(31 reference statements)

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“…Though individual APDs have different respective binding affinities at the serotonin receptors, it has been suggested that APD actions at 5HT2a and 5HT2c receptors in the hypothalamus contribute significantly to iatrogenic weight gain (Ballon et al, 2014 ). In contrast, a recent study showed that polymorphisms in serotonin receptor genes HTR3A and HTR3B were not associated with predicting APD-induced weight gain (Zai et al, 2016 ).…”

Section: Central Nervous System Mechanisms Of Intrinsic and Apd-inducmentioning

confidence: 92%

Intrinsic and Antipsychotic Drug-Induced Metabolic Dysfunction in Schizophrenia

et al. 2017

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For decades, there have been observations demonstrating significant metabolic disturbances in people with schizophrenia including clinically relevant weight gain, hypertension, and disturbances in glucose and lipid homeostasis. Many of these findings pre-date the use of antipsychotic drugs (APDs) which on their own are also strongly associated with metabolic side effects. The combination of APD-induced metabolic changes and common adverse environmental factors associated with schizophrenia have made it difficult to determine the specific contributions of each to the overall metabolic picture. Data from drug-naïve patients, both from the pre-APD era and more recently, suggest that there may be an intrinsic metabolic risk associated with schizophrenia. Nevertheless, these findings remain controversial due to significant clinical variability in both psychiatric and metabolic symptoms throughout patients' disease courses. Here, we provide an extensive review of classic and more recent literature describing the metabolic phenotype associated with schizophrenia. We also suggest potential mechanistic links between signaling pathways associated with schizophrenia and metabolic dysfunction. We propose that, beyond its symptomatology in the central nervous system, schizophrenia is also characterized by pathophysiology in other organ systems directly related to metabolic control.

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Section: Central Nervous System Mechanisms Of Intrinsic and Apd-inducmentioning

confidence: 92%

Intrinsic and Antipsychotic Drug-Induced Metabolic Dysfunction in Schizophrenia

et al. 2017

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“…In a study by Yuan et al [ 38 ], several haplotypes of the promoter region of HTR2C were identified and associated with obesity and diabetes. A pharmacogenetic study of other genes of the serotonergic system ( HTR3A, HTR3B ) did not reveal associations with weight gain induced by antipsychotics [ 39 ].…”

Section: Introductionmentioning

confidence: 99%

Genetic Polymorphisms of 5-HT Receptors and Antipsychotic-Induced Metabolic Dysfunction in Patients with Schizophrenia

Paderina

Boiko

Pozhidaev

et al. 2021

JPM

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Background: Antipsychotic-induced metabolic syndrome (MetS) is a multifactorial disease with a genetic predisposition. Serotonin and its receptors are involved in antipsychotic-drug-induced metabolic disorders. The present study investigated the association of nine polymorphisms in the four 5-hydroxytryptamine receptor (HTR) genes HTR1A, HTR2A, HTR3A, and HTR2C and the gene encoding for the serotonin transporter SLC6A4 with MetS in patients with schizophrenia. Methods: A set of nine single-nucleotide polymorphisms of genes of the serotonergic system was investigated in a population of 475 patients from several Siberian regions (Russia) with a clinical diagnosis of schizophrenia. Genotyping was performed and the results were analyzed using chi-square tests. Results: Polymorphic variant rs521018 (HTR2C) was associated with higher body mass index in patients receiving long-term antipsychotic therapy, but not with drug-induced metabolic syndrome. Rs1150226 (HTR3A) was also associated but did not meet Hardy–Weinberg equilibrium. Conclusions: Our results indicate that allelic variants of HTR2C genes may have consequences on metabolic parameters. MetS may have too complex a mechanistic background to be studied without dissecting the syndrome into its individual (causal) components.

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