Reevaluation of Serum Arylesterase Activity in Neurodevelopmental Disorders.
Ignazio Stefano Piras, Stefano Gabriele, Laura Altieri, Federica Lombardi, Roberto Sacco, Carla Lintas, Barbara Manzi, Paolo Curatolo, Maria Nobile, Catia Rigoletto, Massimo Molteni, Antonio M Persico
Author Information
Ignazio Stefano Piras: Unit of Child & Adolescent Neuropsychiatry, University Campus Bio-Medico, I-00128 Rome, Italy.
Stefano Gabriele: Unit of Child & Adolescent Neuropsychiatry, University Campus Bio-Medico, I-00128 Rome, Italy.
Laura Altieri: Unit of Child & Adolescent Neuropsychiatry, University Campus Bio-Medico, I-00128 Rome, Italy.
Federica Lombardi: Unit of Child & Adolescent Neuropsychiatry, University Campus Bio-Medico, I-00128 Rome, Italy.
Roberto Sacco: Unit of Child & Adolescent Neuropsychiatry, University Campus Bio-Medico, I-00128 Rome, Italy.
Carla Lintas: Unit of Child & Adolescent Neuropsychiatry, University Campus Bio-Medico, I-00128 Rome, Italy. ORCID
Barbara Manzi: Unit of Child and Adolescent Neuropsychiatry, University of Rome "Tor Vergata", I-00133 Rome, Italy.
Paolo Curatolo: Unit of Child and Adolescent Neuropsychiatry, University of Rome "Tor Vergata", I-00133 Rome, Italy.
Maria Nobile: Child Psychopathology Unit, Scientific Institute, IRCCS 'E. Medea', I-23842 Bosisio Parini (LC), Italy.
Catia Rigoletto: Child Psychopathology Unit, Scientific Institute, IRCCS 'E. Medea', I-23842 Bosisio Parini (LC), Italy.
Massimo Molteni: Child Psychopathology Unit, Scientific Institute, IRCCS 'E. Medea', I-23842 Bosisio Parini (LC), Italy.
Antonio M Persico: Interdepartmental Program "Autism 0-90", "G. Martino" University Hospital, University of Messina, I-98122 Messina, Italy.
Organophosphate compounds (OPs) interfere with neurodevelopment and are neurotoxic for humans and animals. They are first biotransformed to the more toxic oxon form, and then hydrolyzed to specific metabolites by the enzyme paraoxonase/arylesterase, encoded by the gene located on human chr. 7q21.3. In autism spectrum disorder (ASD) and in attention-deficit/hyperactivity disorder (ADHD), a correlation between OP exposure and disease onset has been reported. In this case-control study, we aimed to replicate our previous work showing reduced levels of serum PON1 arylesterase activity in Italian and Caucasian-American ASD samples, and to extend our analysis to other neurodevelopmental disorders, namely ADHD and developmental language disorder (DLD), also known as specific language impairment (SLI). The arylesterase activity, measured using standard spectrophotometric methods, is significantly reduced in the ADHD, and not in the ASD sample compared with the controls. Our previous results seemingly stem from spuriously high arylesterase levels in the former control sample. Finally, genotyping SNPs rs705379 and rs662 using TDI-FP, a significant effect of rs705379 alleles on the serum arylesterase activity is observed in all of the subgroups tested, regardless of diagnosis, as well as a lack of association between gene polymorphisms and ASD/ADHD susceptibility in the Italian population. In summary, the serum arylesterase activity is reduced in children and adolescents with ADHD, and this reduction is not due to the functional gene variants assessed in this study. Based on previous literature, it may more likely reflect enhanced oxidative stress than specific genetic underpinnings.
