Pharmacogenomic Medicine in Autism: Challenges and Opportunities

Abstract

Autism spectrum disorder (ASD) affects 1 in 68 children in the US and is distinguished by core deficits in social interactions. Developing pharmacologic treatments for ASD is complicated by clinical and genetic heterogeneity. Although pharmacological treatments have not been shown to be effective in treating the core symptoms of ASD (i.e., social deficits), there is evidence that the burden of emotional and behavioral problems can be reduced with pharmacotherapy. Numerous randomized clinical trials of treatments for the core ASD deficits have been conducted; however, most have provided inconclusive results due to the substantial variation in treatment response. Variation also exists in the considerable metabolic side effects of many of the current treatments. Some of this variation may be explained by differences in the underlying genetic pathways. Exploiting the link between genetic heterogeneity and clinical variation associated with behavioral problems may provide an opportunity for targeted treatment of ASD. In this review, we summarize the recent findings from pharmacogenomics studies of ASD and suggest further how understanding how genetic liability modifies the effect of drugs may present an opportunity to address the challenges of personalized medicine in autism.

Pharmacogenomic Study Reveals New Variants of Drug Metabolizing Enzyme and Transporter Genes Associated with Steady-State Plasma Concentrations of Risperidone and 9-Hydroxyrisperidone in Thai Autism Spectrum Disorder Patients

“…In addition, autism patients show symptoms like irritability, aggressive attitude toward other or property, anxiety, self-injurious behavior, hyperactivity, and severe temper tantrums (Ghosh et al, 2013; Bowers et al, 2015). Risperidone, an atypical antipsychotic, is approved by the Food and Drug Administration (FDA) to treat disruptive behaviors associated with autism in children and adolescents(Cohen et al, 2013) demonstrating antagonism at dopamine D 2 , serotonin 5HT 2A , and adrenergic α 2 receptors (Thyssen et al, 2010).…”

A de novo splice site mutation in EHMT1 resulting in Kleefstra syndrome with pharmacogenomics screening and behavior therapy for regressive behaviors

“…Similarly, it is becoming clear that genetic backgrounds can have a profound impact on therapeutic interventions (Bowers et al. ). These genetic variations may not only serve as causative factors, but also govern treatment response and/or metabolic side effects of prevalent treatment regimens (Bowers et al.…”

“…ASD is a complex multigenic disorder with several susceptibility genes although the complex interplay between these genes behind the etiology of this disease has yet to be fully understood (Miles 2011). Similarly, it is becoming clear that genetic backgrounds can have a profound impact on therapeutic interventions (Bowers et al 2015). These genetic variations may not only serve as causative factors, but also govern treatment response and/or metabolic side effects of prevalent treatment regimens (Bowers et al 2015).…”

“…Similarly, it is becoming clear that genetic backgrounds can have a profound impact on therapeutic interventions (Bowers et al 2015). These genetic variations may not only serve as causative factors, but also govern treatment response and/or metabolic side effects of prevalent treatment regimens (Bowers et al 2015). Pharmacogenomic testing of genes that influence drug metabolism can therefore have important implications in effectiveness and potential adverse side effects.…”

Risk factors in autism: Thinking outside the brain

“…To this end, immune-modulating and anti-inflammatory drugs such as corticosteroids have shown some behavioral improvements in open-label trials and case studies of patients with ASD, but these types of treatments should be more targeted toward specific subtypes and validated in larger, more rigorous trials [89]. Another emerging, individualized treatment approach is pharmacogenomics, which aims to use personal genetic information to guide pharmacologic interventions that maximize therapeutic benefits while minimizing side-effects [90]. Oxytocin-based therapies have also been investigated in hopes of improving the social behaviors core to ASD, but again any beneficial effects shown in previous studies need to be replicated in larger trials [91].…”