Varney Lauren, Murtough Stephen, Cotic Marius, Abidoph Rosemary, Chan Lian, Saadullah Khani Noushin, Richards-Belle Alvin, Richards-Brown Maria, Mills Daisy, Panconesi Daniele, Dawda Yogita, Sharma Parveen, Shah Chetan, Secchi Agostina, Nilforooshan Ramin, Mudholkar Santosh, Murdoch Rosie, Molai Jazmin, Griffiths Rebecca, Senthilkumar Suruthy, Blake Helen, Lankshear Steve, McRoberts Jennifer, Pastor Bethany, Thomas Carmel, Richards Sabrina, Welfare-Wilson Alison, Cheung Sai-Bo, Cox Rebecca, Jibero Anita Chinazam, Anad Reanne, Laczik Rebeka, Ghali Sharif, Berry Alex J, Curwen Joanna, Odutoye Koye, Kottalgi Girija, Williams Sally, Wong Solomon, Anandan Nithya, Pius Georgy, Ajiteru Tonye, Clark Victoria, van Driel Philip, Bashir Amir, Court Samantha, Pawsey Minerva, Skowronska Anna, Woodley Jessica, Bramon Elvira
Division of Psychiatry, University College London, London W1T 7NF, UK.
Department of Genetics and Genomic Medicine, UCL Great Ormond Street Institute of Child Health, University College London, London WC1N 1DZ, UK.
Pharmaceuticals (Basel). 2025 Jun 14;18(6):892. doi: 10.3390/ph18060892.
Antipsychotic treatment response varies considerably between individuals, with one potential reason being genetic variation affecting the cytochrome P450 enzymes that metabolise them. : With a diverse sample of 453 participants, we studied the influence of , , and variation on three antipsychotic treatment outcomes: participant-reported adverse antipsychotic drug reactions, health-related quality of life, and the dose of antipsychotic medication prescribed. These measures were taken from the baseline assessment, before a pharmacogenetic intervention was delivered. : Over half of our sample (62.9%) were carriers of an allele associated with altered metabolism of antipsychotic medications on or , the two genes with pharmacogenetic guidelines for antipsychotic medications. Ultrarapid CYP2D6 metabolisers reported significantly lower levels of adverse antipsychotic drug reactions than normal CYP2D6 metabolisers (mean difference: -11.1; 95% confidence interval [CI]: -18.9, -3.3; = 0.00575). There was also suggestive evidence of lower quality of life scores in those carrying one (mean difference: -0.0863; 95% CI: -0.1806, 0.0081; = 0.0731) or two copies (mean difference: -0.0803; 95% CI: -0.1734, 0.0129; = 0.0914) of the -inducible allele. : Our findings suggest that even when looking at a small number of cytochrome P450 genes, carrying an allele associated with altered antipsychotic medication metabolism is relatively common. We also found evidence that the CYP genotype can influence antipsychotic treatment outcomes, specifically adverse drug reactions and quality of life scores.
抗精神病药物治疗反应在个体之间差异很大，一个潜在原因是基因变异影响了代谢这些药物的细胞色素P450酶。在453名参与者的多样化样本中，我们研究了[具体基因1]、[具体基因2]和[具体基因3]变异对三种抗精神病药物治疗结果的影响：参与者报告的抗精神病药物不良反应、健康相关生活质量以及开具的抗精神病药物剂量。这些指标取自基因检测干预实施前的基线评估。我们样本中超过一半（62.9%）是在[具体基因1]或[具体基因2]上携带与抗精神病药物代谢改变相关等位基因的携带者，这两个基因具有抗精神病药物的基因检测指南。超快CYP2D6代谢者报告的抗精神病药物不良反应水平显著低于正常CYP2D6代谢者（平均差异：-11.1；95%置信区间[CI]：-18.9，-3.3；P = 0.00575）。也有提示性证据表明，携带一个（平均差异：-0.0863；95% CI：-0.1806，0.0081；P = 0.0731）或两个拷贝（平均差异：-0.0803；95% CI：-0.1734，0.0129；P = 0.0914）的[具体基因3]诱导型等位基因的个体生活质量得分较低。我们的研究结果表明，即使只观察少数细胞色素P450基因，携带与抗精神病药物代谢改变相关的等位基因也相对常见。我们还发现证据表明，CYP基因型可影响抗精神病药物治疗结果，特别是药物不良反应和生活质量得分。
