A pharmacogenetic risk score for the evaluation of major depression severity under treatment with antidepressants
| Autor: | Kanders, Sofia H., Pisanu, Claudia, Bandstein, Marcus, Jonsson, Jörgen, Castelao, Enrique, Pistis, Giorgio, Gholam-Rezaee, Mehdi, Eap, Chin B., Preisig, Martin, Schiöth, Helgi B., Mwinyi, Jessica |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Adult
Male Pharmacogenomic Variants Pharmacology and Toxicology genetic risk score treatment with antidepressants Polymorphism Single Nucleotide Severity of Illness Index Humans Prospective Studies Research Articles pharmacogenetics Aged Depressive Disorder Major Middle Aged Farmakologi och toxikologi Antidepressive Agents Cytochrome P-450 CYP2C19 Treatment Outcome depression random forest Receptor Serotonin 5-HT1A Female Switzerland Research Article |
| Zdroj: | Drug development research, vol. 81, no. 1, pp. 102-113 Drug Development Research |
| Popis: | The severity of symptoms as well as efficacy of antidepressants in major depressive disorder (MDD) is modified by single nucleotide polymorphisms (SNPs) in different genes, which may contribute in an additive or synergistic fashion. We aimed to investigate depression severity in participants with MDD under treatment with antidepressants in relation to the combinatory effect of selected genetic variants combined using a genetic risk score (GRS). The sample included 150 MDD patients on regular AD therapy from the population‐based Swiss PsyCoLaus cohort. We investigated 44 SNPs previously associated with antidepressant response by ranking them with regard to their association to the Center for Epidemiologic Studies Short Depression Scale (CES‐D) score using random forest. The three top scoring SNPs (rs12248560, rs878567, rs17710780) were subsequently combined into an unweighted GRS, which was included in linear and logistic regression models using the CES‐D score, occurrence of a major depressive episode (MDE) during follow‐up and regular antidepressant treatment during the 6 months preceding follow‐up assessment as outcomes. The GRS was associated with MDE occurrence (p = .02) and ln CES‐D score (p = .001). The HTR1A rs878567 variant was associated with ln CES‐D after adjustment for demographic and clinical variables [p = .02, lower scores for minor allele (G) carriers]. Additionally, rs12248560 (CYP2C19) CC homozygotes showed a six‐fold higher likelihood of regular AD therapy at follow‐up compared to minor allele homozygotes [TT; ultrarapid metabolizers (p = .03)]. Our study suggests that the cumulative consideration of pharmacogenetic risk variants more reliably reflects the impact of the genetic background on depression severity than individual SNPs. |
| Databáze: | OpenAIRE |
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