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- Huezo-Diaz, P, et al.
(author)
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CYP2C19 genotype predicts steady state escitalopram concentration in GENDEP
- 2012
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In: Journal of psychopharmacology (Oxford, England). - : SAGE Publications. - 1461-7285 .- 0269-8811. ; 26:3, s. 398-407
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Journal article (peer-reviewed)abstract
- In vitro work shows CYP2C19 and CYP2D6 contribute to the metabolism of escitalopram to its primary metabolite, N-desmethylescitalopram. We report the effect of CYP2C19 and CYP2D6 genotypes on steady state morning concentrations of escitalopram and N-desmethylescitalopram and the ratio of this metabolite to the parent drug in 196 adult patients with depression in GENDEP, a clinical pharmacogenomic trial. Subjects who had one CYP2D6 allele associated with intermediate metabolizer phenotype and one associated with poor metabolizer (i.e. IM/PM genotypic category) had a higher mean logarithm escitalopram concentration than CYP2D6 extensive metabolizers (EMs) ( p = 0.004). Older age was also associated with higher concentrations of escitalopram. Covarying for CYP2D6 and age, we found those homozygous for the CYP2C19*17 allele associated with ultrarapid metabolizer (UM) phenotype had a significantly lower mean escitalopram concentration (2-fold, p = 0.0001) and a higher mean metabolic ratio ( p = 0.0003) than EMs, while those homozygous for alleles conferring the PM phenotype had a higher mean escitalopram concentration than EMs (1.55-fold, p = 0.008). There was a significant overall association between CYP2C19 genotypic category and escitalopram concentration ( p = 0.0003; p = 0.0012 Bonferroni corrected). In conclusion, we have demonstrated an association between CYP2C19 genotype, including the CYP2C19*17 allele, and steady state escitalopram concentration.
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- Power, R. A., et al.
(author)
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Fecundity of Patients With Schizophrenia, Autism, Bipolar Disorder, Depression, Anorexia Nervosa, or Substance Abuse vs Their Unaffected Siblings
- 2013
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In: Jama Psychiatry. - : American Medical Association (AMA). - 2168-622X .- 2168-6238. ; 70:1, s. 22-30
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Journal article (peer-reviewed)abstract
- Context: It is unknown how genetic variants conferring liability to psychiatric disorders survive in the Objectives: To examine the reproductive fitness of patients with schizophrenia and other psychiatric Design: We measured the fecundity of patients with schizophrenia, autism, bipolar disorder, Setting: Population databases in Sweden, including the Multi-Generation Register and the Swedish Participants: In total, 2.3million individuals among the 1950 to 1970 birth cohort in Sweden. Main Outcome Measures: Fertility ratio (FR), reflecting the mean number of children compared with Results: Except for women with depression, affected patients had significantly fewer children (FR range Conclusions: Our results suggest that strong selection exists against schizophrenia, autism, and
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- Tammiste, A, et al.
(author)
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Whole-exome sequencing identifies a polymorphism in the BMP5 gene associated with SSRI treatment response in major depression
- 2013
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In: Journal of psychopharmacology (Oxford, England). - : SAGE Publications. - 1461-7285 .- 0269-8811. ; 27:10, s. 915-920
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Journal article (peer-reviewed)abstract
- Although antidepressants are widely used in the pharmacotherapy of major depressive disorder (MDD), their efficacy is still insufficient as approximately one-third of the patients do not fully recover even after several treatment trials. Inter-individual genetic differences are thought to contribute to the variability in antidepressant response; however, current findings from pharmacogenetic studies are uncertain or not clearly replicated. Here we report the first application of full exome sequencing for the analysis of pharmacogenomics on antidepressant treatment. After 12 weeks of treatment with the selective serotonin re-uptake inhibitor escitalopram, we selected five clear responders and five clear non-responders for exome sequencing. By comparing the allele counts of previously known single nucleotide polymorphisms and novel polymorphisms we selected 38 markers for further genotyping in two independent patient samples treated with escitalopram ( n=116 and n=394). The A allele, carried by approximately 30% of the patients with MDD, of rs41271330 in the bone morphogenetic protein (BMP5) gene showed strong association with worse treatment response in both sample sets ( p=0.001), indicating that this is an promising pharmacogenetic marker for prediction of antidepressant therapeutic outcome.
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