Genetics of second-generation antipsychotic and mood stabilizer-induced weight gain in bipolar disorder

Creta, Elia; Fabbri, Chiara; Serretti, Alessandro

doi:10.1097/fpc.0000000000000144

Cited by 16 publications

(6 citation statements)

References 76 publications

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“…FTO seems to regulate food intake at the hypothalamic level (Tung et al, 2010). Consequently, polymorphisms in the FTO gene have been investigated in relation to AP-induced weight gain, finding independent significant associations between this phenotype and metabolic syndrome (Creta et al, 2015; Reynolds et al, 2013; Roffeei et al, 2014; Song et al, 2014; Tiwari et al, 2011). It is important to note that FTO seems to play a more important role in increasing body weight during chronic AP treatment (Reynolds et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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“…1). These findings are of particular relevance, as LEP was previously found to be associated with weight gain in animal and human investigations (Erez et al, 2011); however, more studies lean towards the idea that the contribution from polymorphisms in LEP may be of minor relevance for AIWG (Creta et al, 2015;Klemettilä et al, 2015;Vasudev et al, 2017).…”

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confidence: 76%

Molecular pathway analysis associates alterations in obesity-related genes and antipsychotic-induced weight gain

Corfitsen

Krantz

Drago

2019

Acta Neuropsychiatr.

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Objective:Antipsychotics often induce excessive weight gain. We hypothesised that individuals with genetic variations related to known obesity-risk genes have an increased risk of excessive antipsychotic-induced weight gain (AIWG). This hypothesis was tested in a subset of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) trial data set.Methods:The CATIE trial compared effects and side effects of five different antipsychotics through an 18-month period. Based on the maximum weight gain recorded, excessive weight gain was defined as >7% weight gain. Cytoscape and GeneMANIA were instrumental in composing a molecular pathway from eight selected genes linked to obesity. Genetic information on a total of 495.172 single-nucleotide polymorphisms (SNPs) were available from 765 (556 males) individuals. Enrichment test was conducted through ReactomePA and Bioconductor. A permutation test was performed, testing the generated pathway against 105 permutated pathways (p ≤ 0.05). In addition, a standard genome-wide association study (GWAS) analysis was performed.Result:GWAS analysis did not detect significant differences related to excessive weight gain. The pathway generated contained 28 genes. A total of 2067 SNPs were significantly expressed (p < 0.01) within this pathway when comparing excessive weight gainers to the rest of the sample. Affected genes including PPARG and PCSK1 were not previously related to treatment-induced weight gain.Conclusions:The molecular pathway composed from high-risk obesity genes was shown to overlap with genetics of patients who gained >7% weight gain during the CATIE trial. This suggests that genes related to obesity compose a pathway of increased risk of excessive AIWG. Further independent analyses are warranted that may confirm or clarify the possible reasoning behind.

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“…A number of candidate genes have been identified by our group as well as others (e.g., [18; 29–32]) and replicated for AIWG. Given the reported synergistic effect of 5-HT3 and cholecystokinin on the regulation of food intake [7] and that our group previously reported an association of the cholecystokinin B receptor gene with AIWG, additional gene-gene interaction (e.g., [33]) and pathway analyses (e.g., [34]) using larger samples may lead to more fruitful research findings that can be translated to better antipsychotic treatment outcome for patients.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2016

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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.

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Genetics of second-generation antipsychotic and mood stabilizer-induced weight gain in bipolar disorder

Cited by 16 publications

References 76 publications

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

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

Molecular pathway analysis associates alterations in obesity-related genes and antipsychotic-induced weight gain

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

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