A new genetic locus for antipsychotic-induced weight gain: A genome-wide study of first-episode psychosis patients using amisulpride (from the OPTiMiSE cohort)

Medientyp: E-Artikel
Titel: A new genetic locus for antipsychotic-induced weight gain: A genome-wide study of first-episode psychosis patients using amisulpride (from the OPTiMiSE cohort)
Beteiligte: ter Hark, Sophie E; Jamain, Stéphane; Schijven, Dick; Lin, Bochao D; Bakker, Mark K; Boland-Auge, Anne; Deleuze, Jean-François; Troudet, Réjane; Malhotra, Anil K; Gülöksüz, Sinan; Vinkers, Christiaan H; Ebdrup, Bjørn H; Kahn, René S; Leboyer, Marion; Luykx, Jurjen J
Erschienen: SAGE Publications, 2020
Erschienen in: Journal of Psychopharmacology
Sprache: Englisch
DOI: 10.1177/0269881120907972
ISSN: 0269-8811; 1461-7285
Schlagwörter: Pharmacology (medical) ; Psychiatry and Mental health ; Pharmacology
Entstehung:
Anmerkungen:
Beschreibung: <jats:sec><jats:title>Background:</jats:title><jats:p> Antipsychotic-induced weight gain is a common and debilitating side effect of antipsychotics. Although genome-wide association studies of antipsychotic-induced weight gain have been performed, few genome-wide loci have been discovered. Moreover, these genome-wide association studies have included a wide variety of antipsychotic compounds. </jats:p></jats:sec><jats:sec><jats:title>Aims:</jats:title><jats:p> We aim to gain more insight in the genomic loci affecting antipsychotic-induced weight gain. Given the variable pharmacological properties of antipsychotics, we hypothesized that targeting a single antipsychotic compound would provide new clues about genomic loci affecting antipsychotic-induced weight gain. </jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p> All subjects included for this genome-wide association study ( n=339) were first-episode schizophrenia spectrum disorder patients treated with amisulpride and were minimally medicated (defined as antipsychotic use <2 weeks in the previous year and/or <6 weeks lifetime). Weight gain was defined as the increase in body mass index from before until approximately 1 month after amisulpride treatment. </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> Our genome-wide association analyses for antipsychotic-induced weight gain yielded one genome-wide significant hit (rs78310016; β=1.05; p=3.66 × 10<jats:sup>−08</jats:sup>; n=206) in a locus not previously associated with antipsychotic-induced weight gain or body mass index. Minor allele carriers had an odds ratio of 3.98 ( p=1.0 × 10<jats:sup>−03</jats:sup>) for clinically meaningful antipsychotic-induced weight gain (⩾7% of baseline weight). In silico analysis elucidated a chromatin interaction with 3-Hydroxy-3-Methylglutaryl-CoA Synthase 1. In an attempt to replicate single-nucleotide polymorphisms previously associated with antipsychotic-induced weight gain, we found none were associated with amisulpride-induced weight gain. </jats:p></jats:sec><jats:sec><jats:title>Conclusion:</jats:title><jats:p> Our findings suggest the involvement of rs78310016 and possibly 3-Hydroxy-3-Methylglutaryl-CoA Synthase 1 in antipsychotic-induced weight gain. In line with the unique binding profile of this atypical antipsychotic, our findings furthermore hint that biological mechanisms underlying amisulpride-induced weight gain differ from antipsychotic-induced weight gain by other atypical antipsychotics. </jats:p></jats:sec>

Nur in Feld suchen:

Zuletzt gesuchte Begriffe: