Genetic Influence on Treatment Response in Children with ASD

Background:  Antipsychotic, antidepressant or stimulant medications are used for the treatment of ASD comorbidity, including symptoms such as aggressiveness, euphoria, anxiety, and depression. However, 30-40% of treated children do not respond to pharmacological treatment and an important proportion present clear deterioration. In addition, 60-70% of them present severe and long-lasting side effects. The reasons behind treatment failure are unclear, and few studies have investigated response determinants in ASD children.

Objectives:  We hypothesised that genetic factors in genes coding for metabolic enzymes and in genes coding for drug targets may contribute to treatment failure. The identification of the genetic factors that influence response and side effects may help to improve treatment in ASD children

Methods:  To test this hypothesis we investigated 32 single nucleotide polymorphisms (SNPs) in 16 genes relevant to pharmacological treatment (CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A5, MDR1, D2, D3, 5-HT1A, 5-HT2A, 5-HT2C, BDNF, COMT, MC4R, LEP and CNR1) in 72 ASD children (88% males, mean age: 8 ± 2.6) treated with a antipsychotics and stimulant medications (risperidone, aripripazole and methylphenidate).

Results:  a genetic variant (rs4244285) in the enzyme CYP2C19, was found associated with treatment-induced weight gain (p<0.04). A trend towards association between a polymorphism in the CNR1 gene (rs489693) and weight gain was also observed (p=0.06). No significant associations were detected with level of treatment efficacy.

Conclusions:  if confirmed, this pharmacogenetic information may help to identify children susceptible of gaining weight during pharmacological treatment, who may benefit from alternative medications and/or palliative interventions.