Article
Biochemistry & Molecular Biology
Vid Matisic, Petar Brlek, Luka Bulic, Vilim Molnar, Marina Dasovic, Dragan Primorac
Summary: This study aimed to investigate the most common alleles, genotypes, and phenotypes in the Croatian population in order to establish national guidelines for drug use. A total of 522 patients were analyzed, and allele frequencies, genotypes, and phenotypes for the investigated genes were determined. Most analyzed genes showed no significant differences between the Croatian and European populations, but some genes exhibited higher frequencies of altered metabolism rates. The findings contribute to optimizing drug use guidelines, potentially reducing adverse drug reactions, and improving therapeutic efficacy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Sumiko Ohnami, Akane Naruoka, Mitsuhiro Isaka, Maki Mizuguchi, Sou Nakatani, Fukumi Kamada, Yuji Shimoda, Ai Sakai, Keiichi Ohshima, Keiichi Hatakeyama, Kouji Maruyama, Yasuhisa Ohde, Hirotsugu Kenmotsu, Toshiaki Takahashi, Yasuto Akiyama, Takeshi Nagashima, Kenichi Urakami, Shumpei Ohnami, Ken Yamaguchi
Summary: The differences in genetic susceptibility to lung adenocarcinoma and squamous cell carcinoma are still not clear. Researchers developed a gene sequencing panel to detect germline variants in these two types of cancer. The study found that certain gene variants were associated with an increased risk of squamous cell carcinoma, while whole-gene deletion was associated with adenocarcinoma.
SCIENTIFIC REPORTS
(2022)
Article
Pharmacology & Pharmacy
Yiran Wang, Jihua Shi, Dapeng Dai, Jianping Cai, Shuanghu Wang, Yun Hong, Shan Zhou, Fangling Zhao, Quan Zhou, Peiwu Geng, Yunfang Zhou, Xue Xu, Qingfeng Luo
Summary: This study evaluated the drug-drug interactions between vonoprazan and eleven common cardiovascular drugs through in vitro and in vivo experiments. The results showed that amlodipine and nifedipine inhibit the metabolism of vonoprazan and amlodipine affects vonoprazan's metabolism in vivo. Molecular simulation suggested that the CYP2B6 enzyme may play a larger role in vonoprazan's metabolism. Therefore, caution should be exercised when prescribing vonoprazan with cardiovascular drugs, especially amlodipine.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Hanqing Chen, Shuang Zhou, Meilin Zhu, Bing Wang, Wei Chen, Lingna Zheng, Meng Wang, Weiyue Feng
Summary: The study reveals that PEI-GNPs have significant effects on hepatic drug-metabolic enzymes and de novo lipogenesis in mice, leading to liver inflammation and partial hepatotoxicity. Therefore, it is crucial to consider the interaction between nanomaterials and the liver and modify the surface chemistry of GNPs before biomedical application.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Emma A. Magavern, David van Heel, Damian Smedley, Mark Caulfield
Summary: This study aimed to explore the possible association between loss-of-function CYP2C19 genotypes and gastrointestinal bleed (GIB) in South Asian participants prescribed antidepressants. The results showed that there was an independent association between antidepressant prescriptions and GIB events, but no relationship between CYP2C19 metabolizer status and GIB in those prescribed antidepressants. Precision dosing based on CYP2C19 genetic information alone is unlikely to reduce GIB prevalence.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Review
Pharmacology & Pharmacy
Bradley Roberts, Zahra Cooper, Stephanie Lu, Susanne Stanley, Bernadette T. Majda, Khan R. L. Collins, Lucy Gilkes, Jennifer Rodger, P. Anthony Akkari, Sean D. Hood
Summary: Pharmacogenetics (PGx) studies how individual genetic differences can affect drug responses. PGx testing can individualize primary care and provide a safer drug prescription model. It has shown promising evidence in improving drug efficacy and reducing toxicity in psychiatry. However, there are barriers hindering its implementation.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Chemistry, Physical
Ying Wang, Baichun Hu, Yupeng Zhang, Dong Wang, Zhaohu Luo, Jian Wang, Fengjiao Zhang
Summary: The study found that the selectivity between CYP1A1 and CYP1B1 mainly depends on the sustainability of pi-pi stacking interactions with phenylalanine residues. Structural flexibility of protein domains orchestrates this interaction, determining binding selectivity. Modification of naphthoflavone compounds to satisfy pi-pi stacking interactions of key phenylalanine residues in CYP1B1 could improve inhibitory selectivity.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2021)
Article
Biochemistry & Molecular Biology
Sonia J. Parikh, Sumit Kamat, Margaret Phillips, Samuel P. Boyson, Thomas Yarbrough, Dylan Davie, Qinghai Zhang, Karen C. Glass, Manish B. Shah
Summary: CYP2C9 enzyme plays a crucial role in metabolizing clinical drugs, and the variant CYP2C9*8 found in individuals of African ancestry affects the clearance of certain drug substrates. The structural and solution characterization of CYP2C9*8 provides valuable insights into the differences in drug binding compared to the wild-type enzyme.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Malte Holmer, Christina de Bruyn Kops, Conrad Stork, Johannes Kirchmair
Summary: This study presents machine learning models for predicting interactions of small organic molecules with CYP enzymes, specifically for classifying substrates and non-substrates. The models show competitive performance in detecting CYP substrates, with a new consensus model achieving high performance. The best models are available for free via the NERDD's CYPstrate module.
Article
Pharmacology & Pharmacy
Julia Carolin Stingl, Jason Radermacher, Justyna Wozniak, Roberto Viviani
Summary: Pharmacogenetic variability in drug metabolism can affect patient vulnerability to side effects and therapeutic failure. This study introduces a systematic statistical methodology to estimate quantitative dose adjustments based on pharmacokinetic differences in pharmacogenetic subgroups. The methodology addresses the challenges of sparse data, incomplete information on phenotypic groups, and heterogeneity of study design. The results demonstrate the effectiveness of the modeling approach in predicting dose adjustments and considering uncertainty.
Article
Pharmacology & Pharmacy
Ales Sorf, Dimitrios Vagiannis, Fahda Ahmed, Jakub Hofman, Martina Ceckova
Summary: This study found that dabrafenib inhibits ABCG2 and ABCB1 transporters and also inhibits CYP2C8, CYP2C9, CYP3A4, and CYP3A5 enzymes. Additionally, dabrafenib increases the mRNA levels of ABCB1, ABCG2, ABCC1, and CYP3A4. These findings suggest that caution should be taken when using dabrafenib in patients with polypharmacy, but its interactions with other drugs could be utilized to improve the treatment outcome of drug-resistant cancer.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Giovanna Gentile, Ottavia De Luca, Antonio Del Casale, Gerardo Salerno, Maurizio Simmaco, Marina Borro
Summary: Improper drug prescription is a major problem leading to drug-related harms and healthcare resource wastage. Through genomic profiling, we found that only 14.8% of Italian subjects had a fully normal cytochrome profile, while 26.5% had combined cytochrome dysfunction. The discussion focuses on the potential benefits of comprehensive pharmacogenomic testing in polytreated patients to improve drug selection.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Yabin Duan, Junbo Zhu, Jianxin Yang, Wenqi Gu, Xue Bai, Guiqin Liu, Li Xiangyang
Summary: The systematic review found that miRNA plays a key role in the expression changes of drug metabolizing enzymes and transporters under hypoxia, with hypoxia potentially causing both upregulation and downregulation of miRNA expression, and controversial effects on CYP450 activity.
CURRENT DRUG METABOLISM
(2021)
Article
Genetics & Heredity
Michael Sayer, Ashley Duche, Trang Jenny Tran Nguyen, Michelle Le, Kunj Patel, Jacqueline Vu, Danny Pham, Brianne Vernick, Richard Beuttler, Don Roosan, Moom R. Roosan
Summary: Although pharmacogenomics (PGx) has the potential to improve patient outcomes, its application is not yet routine. A study evaluated the detection rate of currently available combinatorial PGx (CPGx) tests based on cytochrome P450 (CYP) gene variants, showing significant variation across ethnic groups. Therefore, the patient's ethnic background should be carefully considered in selecting CPGx tests.
FRONTIERS IN GENETICS
(2021)
Article
Anesthesiology
Catherine Chanfreau-Coffinier, Sony Tuteja, Leland E. Hull, Sally MacDonald, Olga Efimova, Jill Bates, Deepak Voora, David W. Oslin, Scott L. DuVall, Julie A. Lynch
Summary: The response to analgesic therapy is influenced by various factors, including genetics and drug interactions. This study aimed to evaluate the potential impact of pharmacogenetic (PGx) testing on the care of Veterans with noncancer pain who were prescribed opioids metabolized by the CYP2D6 gene. The results showed that a significant proportion of patients were at an elevated risk for undesirable responses to their opioid medication based on predicted phenotypes and drug-drug interactions. However, CYP2D6 testing was infrequently used, and the results were mainly utilized to optimize antidepressant treatments rather than pain medications. The findings suggest that utilizing PGx testing along with consideration of phenoconversion may enhance the precision medicine approach to pain management in Veterans.
Article
Psychiatry
Philip G. Tibbo, Kyle A. McKee, Jeffrey H. Meyer, Candice E. Crocker, Katherine J. Aitchison, Raymond W. Lam, David N. Crockford
Summary: The position statement was developed by the Research Committee of the Canadian Psychiatric Association and approved by the Board of Directors on May 13, 2020.
CANADIAN JOURNAL OF PSYCHIATRY-REVUE CANADIENNE DE PSYCHIATRIE
(2021)
Article
Pharmacology & Pharmacy
Amanda Buchner, Xiuying Hu, Katherine J. Aitchison
Summary: The research validates efficient detection methods for HLA-B*15:02 and HLA-A*31:01 haplotypes using TaqMan assays that detect single nucleotide variants.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Psychiatry
Eric C. Chan, Keanna Wallace, Esther H. Yang, Leslie Roper, Garima Aryal, Rohit J. Lodhi, Andrius Baskys, Richard Isenberg, Patrick Carnes, Bradley Green, Katherine J. Aitchison
Summary: This study evaluated the internal consistency of the self-report components of the Suicide Ideation and Behavior Assessment Tool (SIBAT) and validated it against relevant elements of the Mini International Neuropsychiatric Interview (MINI). The results showed high internal consistency in modules 2, 3, and 5 of SIBAT, significant associations between each item in module 5 and the corresponding item in MINI, and moderate correlations between the sum of scores from modules 2 and 3 with MINI's assessment of suicide risk.
PSYCHIATRY RESEARCH
(2021)
Article
Psychiatry
Eric C. Chan, Keanna Wallace, Esther H. Yang, Leslie Roper, Garima Aryal, Rohit J. Lodhi, Richard Isenberg, Patrick Carnes, Andrius Baskys, Bradley Green, Katherine J. Aitchison
Summary: The study found that data collected via mobile device showed good concurrent validity with data collected via personal computer in assessing suicidality, but there were differences in scale completion and responses to questions between the two groups.
PSYCHIATRY RESEARCH
(2022)
Article
Psychology, Clinical
Ole Koehler-Forsberg, Robert Keers, Rudolf Uher, Joanna Hauser, Wolfgang Maier, Marcella Rietschel, Peter McGuffin, Anne E. Farmer, Katherine J. Aitchison, Ole Mors
Summary: This study suggests that there may be correlations between personality traits and antidepressant treatment response, but these correlations may be confounded by differential rates of discontinuation.
PSYCHOLOGICAL MEDICINE
(2023)
Article
Psychiatry
Beatriz Carvalho Henriques, Avery Buchner, Xiuying Hu, Yabing Wang, Vasyl Yavorskyy, Keanna Wallace, Rachael Dong, Kristina Martens, Michael S. Carr, Bahareh Behroozi Asl, Joshua Hague, Sudhakar Sivapalan, Wolfgang Maier, Mojca Z. Dernovsek, Neven Henigsberg, Joanna Hauser, Daniel Souery, Annamaria Cattaneo, Ole Mors, Marcella Rietschel, Gerald Pfeffer, Stacey Hume, Katherine J. Aitchison
Summary: This study aimed to cross-validate various technologies for genotyping CYP2D6 and CYP2C19, providing a wide range of assay options, automated haplotype translation, and workflow optimization to enhance feasibility for clinical implementation of these genetic profiles.
TRANSLATIONAL PSYCHIATRY
(2021)
Article
Psychiatry
Sidney Yap, Jessica Luki, Christopher C. Hanstock, Peter Seres, Tami Shandro, Sarah E. C. Hanstock, Alynna Lirette, Huaying (Helen) Zhao, Katherine J. Aitchison, Jean-Michel Le Melledo
Summary: The study found that perimenopause is associated with decreases in MPFC Glu levels, which may contribute to the increased risk of experiencing depression during this period. Further research should focus on assessing MPFC Glu levels in perimenopausal women suffering from MD.
FRONTIERS IN PSYCHIATRY
(2021)
Correction
Psychiatry
Beatriz Carvalho Henriques, Avery Buchner, Xiuying Hu, Yabing Wang, Vasyl Yavorskyy, Keanna Wallace, Rachael Dong, Kristina Martens, Michael S. Carr, Bahareh Behroozi Asl, Joshua Hague, Sudhakar Sivapalan, Wolfgang Maier, Mojca Z. Dernovsek, Neven Henigsberg, Joanna Hauser, Daniel Souery, Annamaria Cattaneo, Ole Mors, Marcella Rietschel, Gerald Pfeffer, Stacey Hume, Katherine J. Aitchison
TRANSLATIONAL PSYCHIATRY
(2022)
Article
Clinical Neurology
Kim H. Tran, Jessica Luki, Sarah Hanstock, Christopher C. Hanstock, Peter Seres, Katherine Aitchison, Tami Shandro, Jean-Michel Le Melledo
Summary: This study suggests that perimenopause is associated with decreased GABA levels in the medial prefrontal cortex, potentially contributing to the risk of developing a major depressive episode during perimenopause.
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
(2023)
Article
Substance Abuse
Shui Jiang, Keanna Wallace, Esther Yang, Leslie Roper, Garima Aryal, Dawon Lee, Rohit J. Lodhi, Randolph Arnau, Rick Isenberg, Bradley Green, David Wishart, Katherine J. Aitchison
Summary: This study aimed to investigate the association between problematic sexual behavior (PSB), addictive disorders, impulse control, and compulsivity. The findings suggest that factors such as compulsive buying, internet addiction, OCD, attention deficit, childhood trauma, and male gender are associated with PSB. Furthermore, OCD shows a different pattern compared to other factors.
JOURNAL OF ADDICTION MEDICINE
(2023)
Article
Psychiatry
Kim H. Tran, Jessica Luki, Sarah Hanstock, Christopher C. Hanstock, Peter Seres, Katherine Aitchison, Tami Shandro, Jean-Michel Le Melledo
Summary: The perimenopause is associated with an increased risk of major depression, but the GABA+ and Glu ratios in the LDLPFC during perimenopause are not related to depression.
FRONTIERS IN PSYCHIATRY
(2022)
Meeting Abstract
Neurosciences
Sidney Yap, Jessica Luki, Christopher C. Hanstock, Peter Seres, Tami Shandro, Sarah Hanstock, Alynna Lirette, Huaying (Helen) Zhaoa, Katherine J. Aitchison, Jean-Michel Le Melledo
JOURNAL OF PSYCHIATRY & NEUROSCIENCE
(2022)
Article
Neurosciences
Oliver Pain, Karen Hodgson, Vassily Trubetskoy, Stephan Ripke, Victoria S. Marshe, Mark J. Adams, Enda M. Byrne, Adrian I. Campos, Tania Carrillo-Roa, Annamaria Cattaneo, Thomas D. Als, Daniel Souery, Mojca Z. Dernovsek, Chiara Fabbri, Caroline Hayward, Neven Henigsberg, Joanna Hauser, James L. Kennedy, Eric J. Lenze, Glyn Lewis, Daniel J. Mueller, Nicholas G. Martin, Benoit H. Mulsant, Ole Mors, Nader Perroud, David J. Porteous, Miguel E. Renteria, Charles F. Reynolds, Marcella Rietschel, Rudolf Uher, Eleanor M. Wigmore, Wolfgang Maier, Naomi R. Wray, Katherine J. Aitchison, Volker Arolt, Bernhard T. Baune, Joanna M. Biernacka, Guido Bondolfi, Katharina Domschke, Masaki Kato, Qingqin S. Li, Yu-Li Liu, Alessandro Serretti, Shih-Jen Tsai, Gustavo Turecki, Richard Weinshilboum, Andrew M. McIntosh, Cathryn M. Lewis
Summary: Antidepressant response is influenced by common genetic variation, has a genetic overlap with schizophrenia and educational attainment, and provides a useful resource for future research.
BIOLOGICAL PSYCHIATRY: GLOBAL OPEN SCIENCE
(2022)
Review
Pharmacology & Pharmacy
Chad A. Bousman, Susanne A. Bengesser, Katherine J. Aitchison, Azmeraw T. Amare, Harald Aschauer, Bernhard T. Baune, Bahareh Behroozi Asl, Jeffrey R. Bishop, Margit Burmeister, Boris Chaumette, Li-Shiun Chen, Zachary A. Cordner, Juergen Deckert, Franziska Degenhardt, Lynn E. DeLisi, Lasse Folkersen, James L. Kennedy, Teri E. Klein, Joseph L. McClay, Francis J. McMahon, Richard Musil, Nancy L. Saccone, Katrin Sangkuhl, Robert M. Stowe, Ene-Choo Tan, Arun K. Tiwari, Clement C. Zai, Gwyneth Zai, Jianping Zhang, Andrea Gaedigk, Daniel J. Mueller
Summary: The implementation of pharmacogenomic testing in psychiatry is limited, but specific genes have been identified to guide the selection and dosing of certain antidepressant and antipsychotic medications.
PHARMACOPSYCHIATRY
(2021)
