Abstract：
This case comparison illustrates pharmacogenetic testing in psychotropic and clinical management in relation to the ABCB1 gene, which encodes the P-glycoprotein transporter affecting blood-brain barrier (BBB) permeability. Two pediatric patients (9 and 11 years old) were selected for similar clinical presentations with opposing ABCB1 genotype, while they were identically matched for key CYP450, dopaminergic and serotonergic genes (CYP2C9, CYP2C19, DRD2, SLC6A4, 5HTR2A). Case A was functional for the ABCB1 gene (G/G rs1045642), suggesting that the BBB had a functional P-glycoprotein transporter. Case B was subfunctional for the ABCB1 gene (A/A rs1045642), suggesting that the patient\'s BBB may be permeable to psychotropic drugs. Case A had more medication trials and dose adjustments than Case B. Case A had two inpatient admissions and interspersed emergency room visits, while case B had none.
The focus of this case comparison report is the ABCB1 gene in child psychiatry and its role in drug efficacy and side effects. ABCB1 encodes the P-glycoprotein transporter of the blood–brain barrier (BBB). As antidepressants must cross the BBB to act on the brain, differences in the functionality of ABCB1 may lead to variable brain concentrations of antidepressants and subsequent variability in therapeutic response. Selecting the cases for comparison with opposing functionality at the ABCB1 gene, while matching for key CYP450, dopaminergic and serotonergic genes (CYP2C9, CYP2C19, DRD2, SLC6A4, 5HTR2A), was the approach utilized. The outcomes of case A and case B reflected pharmacogenetic and clinical contrasts, including patient responses to antidepressants and antipsychotics, susceptibility to adverse effects and differences in the severity of symptoms. These effects on antidepressants and antipsychotics are important because a permeable BBB will allow these drugs to cross into the brain to exert their effect, thus improving clinical outcomes, reducing hospitalizations and emergency room visits and minimizing drug trials and dosage changes. More clinical attention and research are needed for the BBB\'s involvement in psychiatric disease and for the P-glycoprotein transporter as a chemical gatekeeper to the brain. Pharmacogenetic testing for ABCB1 polymorphisms could be considered to inform psychotropic prescribing for the most vulnerable patients in child and adolescent psychiatry in the near future.
The focus of this case comparison report is the ABCB1 gene in child psychiatry and its role in drug efficacy and side effects. ABCB1 encodes the P-glycoprotein transporter of the blood–brain barrier (BBB). As antidepressants must cross the BBB to act on the brain, differences in the functionality of ABCB1 may lead to variable brain concentrations of antidepressants and subsequent variability in therapeutic response. Selecting the cases for comparison with opposing functionality at the ABCB1 gene, while matching for key CYP450, dopaminergic and serotonergic genes (CYP2C9, CYP2C19, DRD2, SLC6A4, 5HTR2A), was the approach utilized. The outcomes of case A and case B reflected pharmacogenetic and clinical contrasts, including patient responses to antidepressants and antipsychotics, susceptibility to adverse effects and differences in the severity of symptoms. These effects on antidepressants and antipsychotics are important because a permeable BBB will allow these drugs to cross into the brain to exert their effect, thus improving clinical outcomes, reducing hospitalizations and emergency room visits and minimizing drug trials and dosage changes. More clinical attention and research are needed for the BBB\'s involvement in psychiatric disease and for the P-glycoprotein transporter as a chemical gatekeeper to the brain. Pharmacogenetic testing for ABCB1 polymorphisms could be considered to inform psychotropic prescribing for the most vulnerable patients in child and adolescent psychiatry in the near future.
摘要：
此案例比较说明了与ABCB1基因相关的精神和临床管理中的药物遗传学测试，其编码影响血脑屏障(BBB)通透性的P-糖蛋白转运体。两名儿科患者（9岁和11岁）被选择为具有相反ABCB1基因型的相似临床表现，而关键CYP450，多巴胺能和5-羟色胺能基因（CYP2C9，CYP2C19，DRD2，SLC6A4，5HTR2A）相同。病例A具有ABCB1基因的功能（G/Grs1045642），提示BBB具有功能性P-糖蛋白转运蛋白。病例B是ABCB1基因的亚功能（A/Ars1045642），提示患者的血脑屏障可能对精神药物具有渗透性。病例A比病例B有更多的药物试验和剂量调整。病例A有两次住院和穿插急诊室就诊。而病例B没有。
本病例比较报告的重点是ABCB1基因在儿童精神病学中的作用及其在药物疗效和副作用中的作用。ABCB1编码血脑屏障(BBB)的P-糖蛋白转运蛋白。因为抗抑郁药必须穿过血脑屏障才能作用于大脑，ABCB1功能的差异可能导致不同的抗抑郁药的脑浓度和随后的治疗反应的差异.选择病例与ABCB1基因的相反功能进行比较，同时匹配关键CYP450，多巴胺能和5-羟色胺能基因（CYP2C9，CYP2C19，DRD2，SLC6A4，5HTR2A），是使用的方法。病例A和病例B的结果反映了药物遗传学和临床对照，包括患者对抗抑郁药和抗精神病药的反应，对不良反应的易感性和症状严重程度的差异。这些对抗抑郁药和抗精神病药的影响很重要，因为渗透性BBB将允许这些药物进入大脑发挥其作用，从而改善临床结果，减少住院和急诊室就诊，并尽量减少药物试验和剂量变化。需要更多的临床关注和研究BBB参与精神疾病和P-糖蛋白转运蛋白作为大脑的化学看门人。可以考虑对ABCB1多态性进行药物遗传学测试，以在不久的将来为儿童和青少年精神病学中最脆弱的患者提供精神处方。
本病例比较报告的重点是ABCB1基因在儿童精神病学中的作用及其在药物疗效和副作用中的作用。ABCB1编码血脑屏障(BBB)的P-糖蛋白转运蛋白。因为抗抑郁药必须穿过血脑屏障才能作用于大脑，ABCB1功能的差异可能导致不同的抗抑郁药的脑浓度和随后的治疗反应的差异.选择病例与ABCB1基因的相反功能进行比较，同时匹配关键CYP450，多巴胺能和5-羟色胺能基因（CYP2C9，CYP2C19，DRD2，SLC6A4，5HTR2A），是使用的方法。病例A和病例B的结果反映了药物遗传学和临床对照，包括患者对抗抑郁药和抗精神病药的反应，对不良反应的易感性和症状严重程度的差异。这些对抗抑郁药和抗精神病药的影响很重要，因为渗透性BBB将允许这些药物进入大脑发挥其作用，从而改善临床结果，减少住院和急诊室就诊，并尽量减少药物试验和剂量变化。需要更多的临床关注和研究BBB参与精神疾病和P-糖蛋白转运蛋白作为大脑的化学看门人。可以考虑对ABCB1多态性进行药物遗传学测试，以在不久的将来为儿童和青少年精神病学中最脆弱的患者提供精神处方。
