Introduction
Autism spectrum disorders (ASDs) are pervasive neurodevelopmental disorders characterized by deficits in communication and social interactions, as well as the presence of stereotypic behaviors.1, 2, 3 Numerous gene mutations have been identified in patients with ASD, but no direct link has so far been uncovered except for a small percentage of cases associated with Tuberous Sclerosis, Fragile X syndrome, Rett syndrome and PTEN deficiency.4, 5 As a result, even though there are a number of genetically-engineered mice with phenotypes resembling autism,6 they do not adequately reflect ASD and there is an urgent need for appropriate animal ‘models’ of ASD.7 In fact, mouse ‘models’ are increasingly considered unreliable with respect to inflammatory human diseases.8 We recently reported that a small number of bull terriers develop symptoms consistent with autism and have increased serum neurotensin (NT) and corticotropin-releasing hormone (CRH), also found to be elevated in children with ASD.9
ASD may affect as many as 1 in 45 children in the USA,10 but the global prevalence is still under-recognized.11 The lack of reliable biomarkers12 and specific pathogenesis,13 as well as the existence of subgroups or comorbidities14 (Table 1), makes the development of specific treatments and conducting clinical studies difficult.13 As a result, child and adolescent outpatient mental health services in the USA have increased considerably.15 Moreover, the annual economic burden for ASD was recently estimated at $268 billion for 2015 and is projected to reach $416 billion in 2025.16