Integrative Genetic Variation, DNA Methylation, and Gene Expression Analysis of Escitalopram and Aripiprazole Treatment Outcomes in Depression: A CAN-BIND-1 Study.
| Autor: | Islam F; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.; Department of Pharmacology & Toxicology, University of Toronto, Toronto, Ontario, Canada., Lisoway A; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada., Oh ES; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada., Fiori LM; McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Verdun, Quebec, Canada., Magarbeh L; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.; Department of Pharmacology & Toxicology, University of Toronto, Toronto, Ontario, Canada., Elsheikh SSM; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada., Kim HK; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada., Kloiber S; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.; Department of Pharmacology & Toxicology, University of Toronto, Toronto, Ontario, Canada.; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada., Kennedy JL; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada., Frey BN; Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada.; St. Joseph's Healthcare Hamilton, Hamilton, Ontario, Canada., Milev R; Department of Psychiatry, Queen's University, Providence Care, Kingston, Ontario, Canada., Soares CN; Department of Psychiatry, Queen's University, Providence Care, Kingston, Ontario, Canada., Parikh SV; Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA., Placenza F; Centre for Mental Health, University Health Network, Toronto, Ontario, Canada., Hassel S; Department of Psychiatry, University of Calgary, Calgary, Alberta, Canada; Mathison Centre for Mental Health Research and Education, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada., Taylor VH; Department of Psychiatry, University of Calgary, Calgary, Alberta, Canada; Mathison Centre for Mental Health Research and Education, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada., Leri F; Department of Psychology and Neuroscience, University of Guelph, Guelph, Ontario, Canada., Blier P; The Royal Institute of Mental Health Research, Ottawa, Ontario, Canada., Uher R; Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada., Farzan F; Mechatronic Systems Engineering, Simon Fraser University, Surrey, British Columbia, Canada., Lam RW; Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada., Turecki G; McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Verdun, Quebec, Canada., Foster JA; Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada.; Centre for Mental Health, University Health Network, Toronto, Ontario, Canada.; St. Joseph's Healthcare Hamilton, Hamilton, Ontario, Canada., Rotzinger S; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.; Department of Psychiatry, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada., Kennedy SH; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.; Centre for Mental Health, University Health Network, Toronto, Ontario, Canada.; Department of Psychiatry, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.; Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Ontario, Canada., Müller DJ; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.; Department of Pharmacology & Toxicology, University of Toronto, Toronto, Ontario, Canada.; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.; Department of Psychiatry, Psychosomatics and Psychotherapy, University Clinic of Würzburg, Würzburg, Germany. |
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| Jazyk: | angličtina |
| Zdroj: | Pharmacopsychiatry [Pharmacopsychiatry] 2024 Sep; Vol. 57 (5), pp. 232-244. Date of Electronic Publication: 2024 Jun 25. |
| DOI: | 10.1055/a-2313-9979 |
| Abstrakt: | Introduction: Little is known about the interplay between genetics and epigenetics on antidepressant treatment (1) response and remission, (2) side effects, and (3) serum levels. This study explored the relationship among single nucleotide polymorphisms (SNPs), DNA methylation (DNAm), and mRNA levels of four pharmacokinetic genes, CYP2C19 , CYP2D6 , CYP3A4 , and ABCB1 , and its effect on these outcomes. Methods: The Canadian Biomarker Integration Network for Depression-1 dataset consisted of 177 individuals with major depressive disorder treated for 8 weeks with escitalopram (ESC) followed by 8 weeks with ESC monotherapy or augmentation with aripiprazole. DNAm quantitative trait loci (mQTL), identified by SNP-CpG associations between 20 SNPs and 60 CpG sites in whole blood, were tested for associations with our outcomes, followed by causal inference tests (CITs) to identify methylation-mediated genetic effects. Results: Eleven cis- SNP-CpG pairs (q<0.05) constituting four unique SNPs were identified. Although no significant associations were observed between mQTLs and response/remission, CYP2C19 rs4244285 was associated with treatment-related weight gain ( q =0.027) and serum concentrations of ESC Discussion: These results elucidate functional mechanisms underlying the established associations between CYP2C19 rs4244285 and ESC pharmacokinetics. This mQTL SNP as a marker for antidepressant-related weight gain needs to be further explored. Competing Interests: Dr. Benicio N. Frey has no conflicts to disclose. Dr. Roumen V. Milev has received consulting and speaking honoraria from AbbVie, Allergan, Eisai, Janssen, KYE Pharmaceuticals, Lallemand, Lundbeck, Otsuka, and Sunovion, and research grants from CAN-BIND, Canadian Institutes of Health Research (CIHR), Janssen, Lallemand, Lundbeck, Nubiyota, Ontario Brain Institute (OBI), and Ontario Mental Health Foundation (OMHF). Dr. Sagar V. Parikh has received research support or consulting income from Aifred, Assurex (Myriad), Janssen, Mensante, Otsuka, Sage, and Takeda. Dr. Stefanie Hassel has no conflicts of interest to disclose. Dr. Pierre Blier received honoraria for participation in advisory boards, giving lectures, and/or expert consultation from Allergan, Bristol Myers Squibb, Janssen, Lundbeck, Otsuka, Pierre Fabre Medicaments, Pfizer and Sunovion; he received grants from Allergan, Janssen, and Lundbeck/Otsuka. Dr. Faranak Farzan received funding from Michael Smith Foundation for Health Research, Natural Sciences and Engineering Research Council of Canada Discovery, and Canadian Institutes of Health Research. Dr. Raymond W. Lam has received honoraria for ad hoc speaking or advising/consulting, or received research funds, from Abbvie, Asia-Pacific Economic Cooperation, BC Leading Edge Foundation, Boehringer-Ingelheim, Canadian Institutes of Health Research (CIHR), Canadian Network for Mood and Anxiety Treatments, Carnot, Healthy Minds Canada, Janssen, Lundbeck, Michael Smith Foundation for Health Research, MITACS, Neurotorium, Ontario Brain Institute (OBI), Otsuka, Pfizer, Unity Health, and VGH-UBCH Foundation. Dr. Gustavo Turecki has received an Investigator-initiated grant from Pfizer Canada, and honoraria from Bristol-Meyers Squibb Canada and Janssen Canada. Dr. Susan Rotzinger has received grant funding from the Ontario Brain Institute (OBI), and Canadian Institutes of Health Research (CIHR), and holds a patent Teneurin C-Terminal Associated Peptides (TCAP) and methods and uses thereof. Dr. Stefan Kloiber has received honorarium for past consultation from EmpowerPharm. Dr. Sidney H. Kennedy has received research funding or honoraria from the following sources: Abbott, Alkermes, Allergan, Bristol-Myers Squibb (BMS), Brain Canada, Canadian Institutes for Health Research (CIHR), Janssen, Lundbeck, Lundbeck Institute, Ontario Brain Institute (OBI), Ontario Research Fund (ORF), Otsuka, Pfizer, Servier, Sunovion and holds stock in Field Trip Health. Dr. Daniel J. Müller reports to be a co-investigator on two pharmacogenetic studies where genetic test kits were provided as in-kind contributions by Myriad Neuroscience. All other authors report no conflicts of interest related to this work. (Thieme. All rights reserved.) |
| Databáze: | MEDLINE |
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