Evidence for alterations in stimulatory G proteins and oxytocin levels in children with autism.
The neurotransmitter oxytocin plays an important role in social affiliation. Low oxytocin levels and defects in the oxytocin receptor have been reported in childhood autism. However, little is known about oxytocin's post-receptor signaling pathways in autism. Oxytocin signals via stimulatory and inhibitory G proteins. c-fos mRNA expression has been used as a marker of OT signaling as well as of G protein signaling. Herein, we hypothesized that oxytocin and its signaling pathways would be altered in children with autism. We measured plasma oxytocin levels by ELISA, G-protein and c-fos mRNA by PCR, and G proteins by immunoblot in cultured peripheral blood mononuclear cells (PBMCs) in children with autism and in age-matched controls. Males with autism displayed elevated oxytocin levels compared to controls (p<0.05). Children with autism displayed significantly higher mRNA for stimulatory G proteins compared to controls (p<0.05). Oxytocin levels correlated strongly positively with c-fos mRNA levels, but only in control participants (p<0.01). Oxytocin, G-protein, and c-fos mRNA levels correlated inversely with measures of social and emotional behaviors, but only in control participants. These data suggest that children with autism may exhibit a dysregulation in oxytocin and/or its signaling pathways.
Division of Endocrinology and Diabetes, Department of Pediatrics, Children's Mercy Hospitals and Clinics, University of Missouri-Kansas City School of Medicine, United States. Electronic address: jjacobson@cmh.edu.
Jill D
JD
Jacobson
Center for Child Health and Development, University of Kansas Medical School, United States.
Kathryn A
KA
Ellerbeck
Center for Child Health and Development, University of Kansas Medical School, United States.
Kelsie A
KA
Kelly
Research Design and Analysis Unit, Life Span Institute, University of Kansas, United States.
Kandace K
KK
Fleming
Center for Child Health and Development, University of Kansas Medical School, United States.
T Rene
TR
Jamison
Center for Child Health and Development, University of Kansas Medical School, United States.
Charles W
CW
Coffey
Center for Child Health and Development, University of Kansas Medical School, United States.
Catherine M
CM
Smith
Center for Child Health and Development, University of Kansas Medical School, United States.
R Matthew
RM
Reese
Division of Endocrinology and Diabetes, Department of Pediatrics, Children's Mercy Hospitals and Clinics, University of Missouri-Kansas City School of Medicine, United States.
Scott A
SA
Sands
D001321:Autistic Disorder / Q000097:blood* / Q000235:genetics*; D016022:Case-Control Studies; D002478:Cells, Cultured; D002648:Child; D002652:Child Behavior; D002675:Child, Preschool; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics* / Q000378:metabolism; D016762:Genes, fos; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D010121:Oxytocin / Q000097:blood*; D018045:Receptors, Oxytocin / Q000235:genetics / Q000378:metabolism
D018045:Receptors, Oxytocin; D010121:Oxytocin; D019205:GTP-Binding Protein alpha Subunits, Gs
ADI-R; ADOS; Autism; Autism in early childhood; G protein; Oxytocin; Signaling