Association study of candidate genes with obesity and metabolic traits in antipsychotic-treated patients with first-episode psychosis over a 2-year period

Abstract

Aims: Patients with a first episode of psychosis (FEP) often display different metabolic disturbances even independently of drug therapy. However, antipsychotic (AP) treatment, especially with second-generation APs, is strongly linked to weight gain, which increases patients’ risk of developing obesity and other metabolic diseases. There is an important genetic risk component that can contribute to the appearance of these disturbances. The aim of the present study was to evaluate the effect of polymorphisms in selected candidate genes on obesity and other anthropometric and metabolic traits in 320 AP-treated FEP patients over the course of a 2-year follow-up. Methods: These patients were recruited in the multicentre PEPs study (Phenotype−genotype and environmental interaction; Application of a predictive model in first psychotic episodes). A total of 127 validated single nucleotide polymorphisms (SNPs) in 18 candidate genes were included in the genetic analysis. Results: After Bonferroni correction, SNPs in ADRA2A, FTO, CNR1, DRD2, DRD3, LEPR and BDNF were associated with obesity, abdominal circumference, triglycerides, HDL cholesterol, and/or percentage of glycated haemoglobin. Conclusions: Although our results should be interpreted as exploratory, they support previous evidence of the impact of these candidate genes on obesity and metabolic status. Further research is required to gain a better knowledge of the genetic variants that can be considered relevant metabolic risk factors. The ability to identify FEP patients at higher risk for these metabolic disturbances would enable clinicians to better select and control their AP treatment.

Metabolic syndrome following a first episode of psychosis: results of a 1-year longitudinal study conducted in metropolitan Lisbon, Portugal

“…Candidate obesity gene variants have been shown to be present in patients who experience a first episode of psychosis (FEP). 26 Moreover, unhealthy dietary habits and low levels of physical activity contribute to the obesity and metabolic disturbances present in patients with psychosis. 21 , 27 Specifically, they consume diets that lack fruit and fiber and are rich in simple sugars.…”

New Insight into the human genetic diversity in North African populations by genotyping of SNPs in DRD3, CSMD1 and NRG1 genes

“…The DRD3 gene (OMIM accession number: *126451) encodes the DRD3 receptor, which is located on chromosome 3q13.3 (Le Coniat et al, 1991 ). The rs6280 and rs3732783 polymorphisms of the DRD3 gene have been extensively studied to demonstrate genetic associations with neuropsychiatric disorders (Gassó et al, 2020 ; Yang et al, 2016 ; Zhang et al, 2011 ). The rs6280 (Gly9Ser) is a functional single nucleotide polymorphism (SNP), which corresponds to a cytosine (C) to thymine (T) substitution leading to a glycine (Gly) to serine (Ser) substitution in the extracellular N‐terminal domain of the receptor (Utsunomiya et al, 2012 ).…”

Search for Possible Associations of FTO Gene Polymorphic Variants with Metabolic Syndrome, Obesity and Body Mass Index in Schizophrenia Patients

“…With rs1421085, rs8050136 and rs9939609, the possible contribution is still obvious. A relationship with (increase in) body weight was found for rs1421085, 63 , 64 rs8050136, 63 , 65–67 and rs9939609 62 , 63 , 66–68 by some authors and not by others (for rs1421085; 66 , 69 , 70 resp. for rs8050136; 64 , 69 , 70 resp.…”