Contrasting ABCB1 pharmacogenetics and psychotropic responses in child and adolescent psychiatry: a case comparison.

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 blood­brain 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.