scholarly journals MC4R rs489693: a clinical risk factor for second generation antipsychotic-related weight gain?

2013 ◽  
Vol 16 (9) ◽  
pp. 2103-2109 ◽  
Author(s):  
Fabian Czerwensky ◽  
Stefan Leucht ◽  
Werner Steimer
Keyword(s):  
Risk Factor ◽  
Weight Gain ◽  
Second Generation ◽  
Genome Wide Association Study ◽  
Analysis Of Covariance ◽  
Clinical Risk Factor ◽  
First Episode ◽  
Mc4r Gene ◽  
A Genome ◽  
Second Generation Antipsychotic

Abstract Weight gain is a therapy limiting and very frequent adverse effect of many second-generation antipsychotic (SGA) drugs. The human melanocortin four receptor (MC4R) is a very promising candidate gene possibly influencing SGA-related weight gain. The rs489693 polymorphism near the MC4R gene was associated with SGA-related weight gain in a genome-wide association study. We tried to replicate these results in our independent naturalistic study population. From 341 Caucasian inpatients receiving at least one SGA drug (olanzapine, clozapine, risperidone, paliperidone, quetiapine or amisulpride), carriers homozygous for the rs489693 A-allele (n = 35) showed a 2.2 times higher weight increase (+2.2 kg) than carriers of the CC-genotype (+1 kg) after 4 wk of treatment (analysis of covariance, p = 0.039). We revealed an even stronger effect in a subpopulation without weight gain inducing co-medication (factor 3.1, +2.8 kg, p = 0.044, (n = 16 of 169)) and in first episode patients (factor 2.7, +2.7 kg, p = 0.017, (n = 13 of 86)). Our results confirm the rs489693 A-allele as a possible risk factor for SGA-related weight gain.

scholarly journals A genome wide association study identifies a lncRna as risk factor for pathological inflammatory responses in leprosy

PLoS Genetics ◽  
2017 ◽  
Vol 13 (2) ◽  
pp. e1006637 ◽  
Author(s):  
Vinicius M. Fava ◽  
Jeremy Manry ◽  
Aurélie Cobat ◽  
Marianna Orlova ◽  
Nguyen Van Thuc ◽  
...  
Keyword(s):  
Risk Factor ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Inflammatory Responses ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome

scholarly journals Use of the second-generation antipsychotic, risperidone, and secondary weight gain are associated with an altered gut microbiota in children

2015 ◽  
Vol 5 (10) ◽  
pp. e652-e652 ◽  
Author(s):  
S M Bahr ◽  
B C Tyler ◽  
N Wooldridge ◽  
B D Butcher ◽  
T L Burns ◽  
...  
Keyword(s):  
Weight Gain ◽  
Gut Microbiota ◽  
Second Generation ◽  
Second Generation Antipsychotic

scholarly journals Anterior Hippocampal–Cortical Functional Connectivity Distinguishes Antipsychotic Naïve First-Episode Psychosis Patients From Controls and May Predict Response to Second-Generation Antipsychotic Treatment

2019 ◽  
Vol 46 (3) ◽  
pp. 680-689 ◽  
Author(s):  
Esther M Blessing ◽  
Vishnu P Murty ◽  
Botao Zeng ◽  
Jijun Wang ◽  
Lila Davachi ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Random Forest ◽  
Treatment Response ◽  
Second Generation ◽  
First Episode Psychosis ◽  
First Episode ◽  
Antipsychotic Treatment ◽  
Episode Psychosis ◽  
Second Generation Antipsychotic ◽  
Cortical Regions

Abstract Background Converging evidence implicates the anterior hippocampus in the proximal pathophysiology of schizophrenia. Although resting state functional connectivity (FC) holds promise for characterizing anterior hippocampal circuit abnormalities and their relationship to treatment response, this technique has not yet been used in first-episode psychosis (FEP) patients in a manner that distinguishes the anterior from posterior hippocampus. Methods We used masked-hippocampal-group-independent component analysis with dual regression to contrast subregional hippocampal–whole brain FC between healthy controls (HCs) and antipsychotic naïve FEP patients (N = 61, 36 female). In a subsample of FEP patients (N = 27, 15 female), we repeated this analysis following 8 weeks of second-generation antipsychotic treatment and explored whether baseline FC predicted treatment response using random forest. Results Relative to HC, untreated FEP subjects displayed reproducibly lower FC between the left anteromedial hippocampus and cortical regions including the anterior cingulate and insular cortex (P < .05, corrected). Anteromedial hippocampal FC increased in FEP patients following treatment (P < .005), and no longer differed from HC. Random forest analysis showed baseline anteromedial hippocampal FC with four brain regions, namely the insular–opercular cortex, superior frontal gyrus, precentral gyrus, and postcentral gyrus predicted treatment response (area under the curve = 0.95). Conclusions Antipsychotic naïve FEP is associated with lower FC between the anterior hippocampus and cortical regions previously implicated in schizophrenia. Preliminary analysis suggests that random forest models based on hippocampal FC may predict treatment response in FEP patients, and hence could be a useful biomarker for treatment development.

Serum Level Measurements Optimize Aripriprazole Treatment in Adolescent Patients

2019 ◽  
Vol 47 (3) ◽  
pp. 261-264 ◽  
Author(s):  
Jochen Gehrmann ◽  
Peter Götz Lampe
Keyword(s):  
Serum Level ◽  
Significant Variation ◽  
Second Generation ◽  
Serum Levels ◽  
First Episode Psychosis ◽  
First Episode ◽  
Off Label ◽  
Episode Psychosis ◽  
Second Generation Antipsychotic ◽  
Over Time

Abstract. 21 minors suffering from first-episode psychosis or related disorders were treated with the second-generation antipsychotic aripriprazole with serum levels being monitored over time. A significant variation of serum levels was observed in about half of the patients. Patients from Africa showed high levels of aripriprazole. In seven patients, i. e. ca. 35 % of the sample, aripriprazole treatment had to be stopped for various reasons. Therefore, serum levels of this antipsychotic (which in Germany is still considered off-label treatment before the age of 18) should be regularly monitored particularly in patients from Africa.

Safety concerns associated with second-generation antipsychotic long-acting injection treatment. A systematic update

2017 ◽  
Vol 36 (2) ◽  
Author(s):  
Salvatore Gentile
Keyword(s):  
Clinical Practice ◽  
Weight Gain ◽  
Second Generation ◽  
Safety Data ◽  
Paliperidone Palmitate ◽  
Cochrane Library ◽  
Pharmacological Intervention ◽  
Psychotic Symptoms ◽  
Second Generation Antipsychotic ◽  
Long Acting

Abstract Background It has been recently suggested that second-generation antipsychotic long-acting injection (SGA-LAIs) are underutilized in clinical practice, despite that their costs significantly impact on national health system budgets. Hence, an updated analysis of safety data shown by SGA-LAIs may contribute to clarify their role in clinical practice. Materials and methods English-language, peer-reviewed articles reporting updated, primary findings on the SGA-LAI safety were identified (updated through an electronic search of five databases – PubMed, EMBASE, PsycInfo, DARE and the Cochrane Library). Results The articles reviewed suggest that the most frequent treatment emergent adverse events (TEAEs) associated with aripiprazole long-acting injection (ARI-LAI) are psychotic symptoms, extrapyramidal symptoms (EPS) and weight gain. Data on olanzapine long-acting injection (OLA-LAI)-associated TEAEs highlight the risk of psychosis, metabolic disturbances and hyperprolactinemia. Four-hundred and forty cases of post-injection delirium/sedation syndrome (PDSS) have also been recorded. Although not reported in reviewed studies, the risk of impulse-control problem and drug reaction with eosinophilia and systemic symptoms (DRESS) ARI- and OLA-associated, respectively, must not be underestimated. With regards paliperidone palmitate 1-month formulation (PP1), the high incidence of clinically relevant weight gain and hyperprolactinemia are both findings of concern. Reviewed data also confirm that the leading cause of death in risperidone long-acting injection (RIS-LAI) clinical trials is suicide. The new 3-month paliperidone palmitate formulation, risperidone sustained release 1-month formulation (RIS-SR1), aripiprazole lauroxil (ARI-LXL) are still lacking exhaustive safety data. Conclusion The risk of specific TEAEs associated with all SGA-LAIs confirms SGA-LAIs do not offer advantages in safety compared with FGA-LAIs or oral antipsychotics and, especially, in early-phase schizophrenia patients. Implementing non pharmacological intervention and strategies can be effective for people with schizophrenia and bipolar disorder who adhere poorly to medication regimens.

scholarly journals Genetics of symptom remission in outpatients with COVID-19

2021 ◽  
Author(s):  
Marie-Pierre Dubé ◽  
Audrey Lemaçon ◽  
Amina Barhdadi ◽  
Louis-Philippe Lemieux Perreault ◽  
Essaïd Oussaïd ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Risk Factor ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Natriuretic Peptide Receptor ◽  
Peptide Receptor ◽  
Mechanistic Pathway ◽  
Genome Wide ◽  
A Genome ◽  
Symptom Remission

ABSTRACTWe conducted a genome-wide association study of time to remission of COVID-19 symptoms in 1723 outpatients with at least one risk factor for disease severity from the COLCORONA clinical trial. We found a significant association at 5p13.3 (rs1173773; P = 4.94 × 10−8) near the natriuretic peptide receptor 3 gene (NPR3). By day 15 of the study, 44%, 54% and 59% of participants with 0, 1, or 2 copies of the effect allele respectively, had symptom remission. In 851 participants not treated with colchicine (placebo), there was a significant association at 9q33.1 (rs62575331; P = 2.95 × 10−8) in interaction with colchicine (P = 1.19 × 10−5) without impact on risk of hospitalisations, highlighting a possibly shared mechanistic pathway. By day 15 of the study, 46%, 62% and 64% of those with 0, 1, or 2 copies of the effect allele respectively, had symptom remission. The findings need to be replicated and could contribute to the biological understanding of COVID-19 symptom remission.

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