An Update on Precision Medicine Advances In Neurodevelopmental Disorders

Abstract

Neurodevelopmental disorders, including autism spectrum disorder (ASD) and attention-deficit/hyper-activity disorder (ADHD), represent a group of conditions that manifest early in child development and produce impairments across multiple domains of functioning. Although a number of pharmacological and psychosocial treatments exist to improve the symptoms associated with these syndromes, treatment advances have lagged. The Precision Medicine Initiative was launched with the goal of revolutionizing medicine by progressing beyond the historical one-size-fits-all approach. In this review, we evaluate current research efforts to personalize treatments for ASD and ADHD. Most pharmacogenetic testing has focused on the cytochrome P450 enzyme family with a particular focus on CYP2D6 and CYP2C19, which are genes that produce an enzyme that acts as a key metabolizer of many prescribed medications. This article provides an update on the state of the field of pharmacogenetics and "therapy-genetics" in the context of ASD and ADHD, and it also encourages clinicians to follow US Food and Drug Administration recommendations regarding pharmacogenetic testing.

Figure 1.

Utility of comparing chromosomal microarray results across patients. Even though patients often have unique genomic profiles of copy number changes, chromosomal microarray (CMA) results may still be informative.This figure shows four unique genomic profiles for a single chromosome.The top profile (A) is from a young child.The bottom three profiles (B, C, D) are results from a clinical database that pairs CMA results with medical records.The clinical team can use this data to assess the need to perform additional testing, to pursue symptom monitoring, or to consult with specialists such as a nephrologist. ADHD, attention-deficit/hyperactivity disorder.

Figure 2.

Workflow for precision medicine.(1) A DNA sample is obtained, most commonly from a blood draw or cheek swab. (2) A subset of cytochrome P450 genes are sequenced. Additional genetic variants at key genomic regulation sequences also may be sequenced. (3) The drug metabolism efficiency of each sequenced gene is estimated for both the maternally and paternally inherited alleles. Next, the combined drug metabolism efficacy is estimated. (4) Patient medical records must be checked to determine if and how any medications or vitamins they are taking inhibit cytochrome P450 activity. (5) Self-report information about patient diet must be collected to assess the impact of certain foods in the diet that may inhibit cytochrome P450 activity. (6) Key physical attributes must be assessed, including weight, age, organ health, and sex, when considering medication and dosage selection. (7) Initial medication and dose are prescribed. (8) Additional monitoring is still necessary to assess treatment responsiveness and drug tolerability.Changes in dosage and/or medication may be necessary because drug metabolism efficacy is not a good predictor of treatment responsiveness.