Abstract:
:Several antipsychotics and antidepressants have been associated with electrocardiogram alterations, the most clinically relevant of which is the heart rate-corrected QT interval (QTc) prolongation, a risk factor for sudden cardiac death. Genetic variants influence drug-induced QTc prolongation and can provide valuable information for precision medicine. The effect of genetic variants on QTc prolongation as well as the possible interaction between polymorphisms and risk medications in determining QTc prolongation were investigated. Medications were classified according to their known risk of inducing QTc prolongation (high-to-moderate, low, and no risk). QTc duration and risk of QTc > median value were investigated in a sample of 77 patients with mood or psychotic disorders being treated with antidepressants and antipsychotics, and who had at least 1 ECG recording. A secondary analysis considered QTc percentage change in patients (n = 25) with 2 ECG recordings. Single-nucleotide polymorphisms previously associated with QTc prolongation during treatment with psychotropic medications were investigated. No association survived after multiple-testing correction. The best results for modulation of QTc duration were identified for rs10808071 (the ABCB1 gene, nominal p = 0.007) when at least 1 medication with a moderate-to-high risk was prescribed, and for rs12029454 (the NOS1AP gene) in patients taking at least 1 medication with a cardiovascular risk (nominal p = 0.008). In the secondary analysis, rs2072413 (the KCNH2 gene) was the top finding for the modulation of QTc percentage change (nominal p = 0.001) when 1 drug with a moderate-to-high risk was added compared to baseline. Despite the limited power of this study, our results suggest that ABCB1, NOS1AP, and KCNH2 may play a role in QTc duration/prolongation during treatment with psychotropic drugs.
journal_name
Neuropsychobiologyjournal_title
Neuropsychobiologyauthors
Corponi F,Fabbri C,Boriani G,Diemberger I,Albani D,Forloni G,Serretti Adoi
10.1159/000493400subject
Has Abstractpub_date
2019-01-01 00:00:00pages
67-72issue
2eissn
0302-282Xissn
1423-0224pii
000493400journal_volume
77pub_type
杂志文章abstract::Schizophrenia is a heterogeneous and multidimensional disorder. The different syndromes or dimensions of this disorder represent distinct pathophysiological processes. Evidence is growing that each of the composite syndromes or dimensions of this disorder is associated with specific validators. This article reviewed n...
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