Abstract

Mental illness is prevalent among hemodialysis (HD) patients. Given that the dopaminergic and serotonergic pathways are involved in the etiology of psychiatric disease, this study evaluated the genetic association of dopamine D4 receptor (DRD4) and serotonin transporter (SLC6A4) genes with psychiatric symptom susceptibility among HD patients. Hospital Anxiety and Depression Scale (HADS) was used to assess anxiety and depressive symptoms among patients (n = 265). Genetic polymorphisms of DRD4 (48 bp VNTR) and SLC6A4 (5-HTTLPR VNTR and rs25531) were examined using a conventional polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique, as appropriate. Significant differences were observed in the distribution of 5-HTTLPR genotypes, SLC6A4 tri-allelic-phased genotype, and DRD4-Exon III VNTR genotypes/alleles between patients with anxiety symptoms versus those with normal/borderline conditions (p<0.05). Binary logistic regression analyses showed that the heterozygous 4,5 VNTR genotype of DRD4 was associated with a higher risk of anxiety symptoms after adjusting for other covariates (odds ratio = 4.25, p = 0.028). None of the studied polymorphisms was linked to depression in HD patients. Collectively, the current findings provide genetic clues to psychopathology in HD patients and suggest that the DRD4 exon III VNTR polymorphism is involved in the etiology of anxiety in this patient population.

Highlights

  • Psychiatric symptoms such as anxiety and depression are common among patients undergoing hemodialysis (HD) [1]

  • The mean depression score (HADS-D) was 8.31 ± 5.2, and 34.7% were defined as cases, while the average anxiety score (HADS-A) was 7.15 ± 4.9, and 27.2% were defined as cases

  • To the best of our knowledge, this study is the first genetic research that has evaluated the potential association of dopamine receptor D4 (DRD4) (48 bp variable number of tandem repeats (VNTR)) and SLC6A4 (5-HTTLPR and rs25531) genetic polymorphisms with psychiatric symptoms among dialysis patients

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Summary

Introduction

Psychiatric symptoms such as anxiety and depression are common among patients undergoing hemodialysis (HD) [1]. These symptoms pose a threat to human health, as they are associated with adverse clinical outcomes such as increased hospitalization and mortality [2, 3]. Multiple factors could be associated with vulnerability to psychiatric symptoms, including sociodemographic, clinical, and environmental elements, lifestyle, and the genetic background [4,5,6]. One study suggested 151 genes that could potentially be involved in major depressive disorder [7]. The dopaminergic and serotonergic pathways are .

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