Serotonergic receptor gene polymorphism and response to selective serotonin reuptake inhibitors in ethnic Malay patients with first episode of major depressive disorder

Badamasi, Ibrahim Mohammed; Lye, Munn Sann; Ibrahim, Normala; Razaq, Nurul Asyikin Abdul; Ling, King Hwa; Stanslas, Johnson

doi:10.1038/s41397-021-00228-6

Cited by 9 publications

(3 citation statements)

References 96 publications

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“…An association between the HTR2A rs6311 T/T genotype and the development of sexual dysfunction is seen in patients being treated for major depressive disorder [ 47 ]. The HTR2A receptor literature shows varying levels of adverse effects: some studies find patients with the rs6311 genotype C/C to suffer more nausea/vomiting, whereas others find less risk of diarrhea, dizziness, and tremor associated with the C/C genotype [ 48 , 49 ].…”

Section: Antidepressantsmentioning

confidence: 99%

Pharmacogenetic Testing for the Pediatric Gastroenterologist: Actionable Drug–Gene Pairs to Know

Sandritter,

Chevalier,

Abt

et al. 2023

Pharmaceuticals

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Gastroenterologists represent some of the earlier adopters of precision medicine through pharmacogenetic testing by embracing upfront genotyping for thiopurine S-methyltransferase nucleotide diphosphatase (TPMT) before prescribing 6-mercaptopurine or azathioprine for the treatment of inflammatory bowel disease. Over the last two decades, pharmacogenetic testing has become more readily available for other genes relevant to drug dose individualization. Common medications prescribed by gastroenterologists for conditions other than inflammatory bowel disease now have actionable guidelines, which can improve medication efficacy and safety; however, a clear understanding of how to interpret the results remains a challenge for many clinicians, precluding wide implementation of genotype-guided dosing for drugs other than 6-mercaptopurine and azathioprine. Our goal is to provide a practical tutorial on the currently available pharmacogenetic testing options and a results interpretation for drug–gene pairs important to medications commonly used in pediatric gastroenterology. We focus on evidence-based clinical guidelines published by the Clinical Pharmacogenetics Implementation Consortium (CPIC®) to highlight relevant drug–gene pairs, including proton pump inhibitors and selective serotonin reuptake inhibitors and cytochrome P450 (CYP) 2C19, ondansetron and CYP2D6, 6-mercaptopurine and TMPT and Nudix hydrolase 15 (NUDT15), and budesonide and tacrolimus and CYP3A5.

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Section: Antidepressantsmentioning

confidence: 99%

Pharmacogenetic Testing for the Pediatric Gastroenterologist: Actionable Drug–Gene Pairs to Know

Sandritter,

Chevalier,

Abt

et al. 2023

Pharmaceuticals

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“…Terock et al and Han et al [ 65 , 66 ] have reported that the C-1019G 5HT1A polymorphism is related to a significant self-destruction of the 5HT1A agonist stimulant response to flibanserin. A relationship between the stimulant response and both this polymorphism [ 67 , 68 ] and Gly272Asp [ 68 ] has been revealed in a number of studies. Albert et al [ 69 ] found that the hereditary impact of the 5HT1A receptor-encoding quality of HTR1A and the serotonin carrier encoding quality of SLC6A4 impacts the clinical results of patients treated with citalopram.…”

Section: Gpcrs and Mood Disordersmentioning

confidence: 99%

“…Several studies have linked the -141C Ins/Del allele to the time or degree of response to antipsychotic drugs, with the -141C Ins allele being associated with a better response; however, other studies have contradicted these findings [ 60 , 104 , 106 , 107 ]. The association between treatment effects and the Taq1A locus [ 108 ], Ser311Cys polymorphism [ 68 ], and His452Tyr polymorphism [ 107 ] has been evaluated in a number of studies. The D3 receptor polymorphism, Ser9Gly, is the most frequently analyzed in relation to the D3 receptor, regardless of a lack of schizophrenic symptoms associated with it [ 109 , 110 ].…”

Section: Schizophrenia and Gpcrsmentioning

confidence: 99%

Insights into the Promising Prospect of G Protein and GPCR-Mediated Signaling in Neuropathophysiology and Its Therapeutic Regulation

Rahman

Islam

Mim

et al. 2022

Oxidative Medicine and Cellular Longevity

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G protein-coupled receptors (GPCRs) are intricately involved in the conversion of extracellular feedback to intracellular responses. These specialized receptors possess a crucial role in neurological and psychiatric disorders. Most nonsensory GPCRs are active in almost 90% of complex brain functions. At the time of receptor phosphorylation, a GPCR pathway is essentially activated through a G protein signaling mechanism via a G protein-coupled receptor kinase (GRK). Dopamine, an important neurotransmitter, is primarily involved in the pathophysiology of several CNS disorders; for instance, bipolar disorder, schizophrenia, Parkinson’s disease, and ADHD. Since dopamine, acetylcholine, and glutamate are potent neuropharmacological targets, dopamine itself has potential therapeutic effects in several CNS disorders. GPCRs essentially regulate brain functions by modulating downstream signaling pathways. GPR6, GPR52, and GPR8 are termed orphan GPCRs because they colocalize with dopamine D1 and D2 receptors in neurons of the basal ganglia, either alone or with both receptors. Among the orphan GPCRs, the GPR52 is recognized for being an effective psychiatric receptor. Various antipsychotics like aripiprazole and quetiapine mainly target GPCRs to exert their actions. One of the most important parts of signal transduction is the regulation of G protein signaling (RGS). These substances inhibit the activation of the G protein that initiates GPCR signaling. Developing a combination of RGS inhibitors with GPCR agonists may prove to have promising therapeutic potential. Indeed, several recent studies have suggested that GPCRs represent potentially valuable therapeutic targets for various psychiatric disorders. Molecular biology and genetically modified animal model studies recommend that these enriched GPCRs may also act as potential therapeutic psychoreceptors. Neurotransmitter and neuropeptide GPCR malfunction in the frontal cortex and limbic-related regions, including the hippocampus, hypothalamus, and brainstem, is likely responsible for the complex clinical picture that includes cognitive, perceptual, emotional, and motor symptoms. G protein and GPCR-mediated signaling play a critical role in developing new treatment options for mental health issues, and this study is aimed at offering a thorough picture of that involvement. For patients who are resistant to current therapies, the development of new drugs that target GPCR signaling cascades remains an interesting possibility. These discoveries might serve as a fresh foundation for the creation of creative methods for pharmacologically useful modulation of GPCR function.

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Biomarker-Guided Tailored Therapy in Major Depression

Perna,

Spiti,

Torti

et al. 2024

Advances in Experimental Medicine and Biology

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Serotonergic receptor gene polymorphism and response to selective serotonin reuptake inhibitors in ethnic Malay patients with first episode of major depressive disorder

Cited by 9 publications

References 96 publications

Pharmacogenetic Testing for the Pediatric Gastroenterologist: Actionable Drug–Gene Pairs to Know

Pharmacogenetic Testing for the Pediatric Gastroenterologist: Actionable Drug–Gene Pairs to Know

Insights into the Promising Prospect of G Protein and GPCR-Mediated Signaling in Neuropathophysiology and Its Therapeutic Regulation

Biomarker-Guided Tailored Therapy in Major Depression

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