title: Elevated serum neurotensin and CRH levels in children with autistic spectrum disorders and tail-chasing Bull Terriers with a phenotype similar to autism.
abstract: Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by defects in communication and social interactions, as well as stereotypic behaviors. Symptoms typically worsen with anxiety and stress. ASD occur in early childhood, often present with regression and have a prevalence of 1 out of 68 children. The lack of distinct pathogenesis or any objective biomarkers or reliable animal models hampers our understanding and treatment of ASD. Neurotensin (NT) and corticotropin-releasing hormone (CRH) are secreted under stress in various tissues, and have proinflammatory actions. We had previously shown that NT augments the ability of CRH to increase mast cell (MC)-dependent skin vascular permeability in rodents. CRH also induced NT receptor gene and protein expression in MCs, which have been implicated in ASD. Here we report that serum of ASD children (4-10 years old) has significantly higher NT and CRH levels as compared with normotypic controls. Moreover, there is a statistically significant correlation between the number of children with gastrointestinal symptoms and high serum NT levels. In Bull Terriers that exhibit a behavioral phenotype similar to the clinical presentation of ASD, NT and CRH levels are also significantly elevated, as compared with unaffected dogs of the same breed. Further investigation of serum NT and CRH, as well as characterization of this putative canine breed could provide useful insights into the pathogenesis, diagnosis and treatment of ASD.
authors.affiliation: Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, Boston, MA, USA.
authors.forename: I
authors.initials: I
authors.lastname: Tsilioni
authors.affiliation: Department of Clinical Sciences, Cummings School of Veterinary Medicine, Tufts University, Grafton, MA, USA.
authors.forename: N
authors.initials: N
authors.lastname: Dodman
authors.affiliation: Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, Boston, MA, USA.
authors.forename: A I
authors.identifier: 0000000188261050
authors.initials: AI
authors.lastname: Petra
authors.affiliation: Second Department of Psychiatry, Attikon General Hospital, Athens University, Athens, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Taliou
authors.affiliation: Second Department of Psychiatry, Attikon General Hospital, Athens University, Athens, Greece.
authors.forename: K
authors.initials: K
authors.lastname: Francis
authors.affiliation: Department of Clinical Sciences, Cummings School of Veterinary Medicine, Tufts University, Grafton, MA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Moon-Fanelli
authors.affiliation: Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, Boston, MA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Shuster
authors.affiliation: 1] Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, Boston, MA, USA [2] Department of Internal Medicine, Tufts University School of Medicine and Tufts Medical Center, Boston, MA, USA [3] Department of Psychiatry, Tufts University School of Medicine and Tufts Medical Center, Boston, MA, USA.
authors.forename: T C
authors.initials: TC
authors.lastname: Theoharides
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000097:blood*; D002675:Child, Preschool; D003346:Corticotropin-Releasing Hormone / Q000097:blood*; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D006801:Humans; D008297:Male; D009496:Neurotensin / Q000097:blood*; D010641:Phenotype; D013239:Stereotyped Behavior
chemical_list: D009496:Neurotensin; D003346:Corticotropin-Releasing Hormone