Article

Scientists probe oxytocin therapy for social deficits in autism, schizophrenia.

JAMA The Journal of the American Medical Association (Impact Factor: 30.39). 02/2011; 305(7):659-61. DOI: 10.1001/jama.2011.117
Source: PubMed
2 Followers
 · 
81 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Previous findings have shown that individuals with autism spectrum disorder (ASD) evince greater intra-individual variability (IIV) in their sensory-evoked fMRI responses compared to typical control participants. We explore the robustness of this finding with a new sample of high-functioning adults with autism. Participants were presented with visual, somatosensory and auditory stimuli in the scanner whilst they completed a one-back task. While ASD and control participants were statistically indistinguishable with respect to behavioral responses, the new ASD group exhibited greater IIV relative to controls. We also show that the IIV was equivalent across hemispheres and remained stable over the duration of the experiment. This suggests that greater cortical IIV may be a replicable characteristic of sensory systems in autism.
    Journal of Autism and Developmental Disorders 10/2014; 45(5). DOI:10.1007/s10803-014-2276-6 · 3.34 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Increasing evidence suggests that the nonapeptide, oxytocin (OT), helps shape social and affiliative behaviors not only in lower mammals but also in humans. Recently, an essential mediator of brain OT release has been discovered, ADP-ribosyl cyclase and/or CD38. We have subsequently shown that polymorphisms across the CD38 gene are associated with autism spectrum disorders (ASD). Notably, CD38 expression in lymphoblastoid cells (LBC) is reduced in cell lines derived from ASD subjects compared to parental cell lines. Intriguingly, a correlation was observed between CD38 expression and measures of social function in ASD. Finally, we have shown that all-trans retinoic acid (ATRA), a known inducer of CD38 transcription, can rescue low CD38 expressing LBC lines derived from ASD subjects and restore normal levels of transcription of this ectoenzyme providing 'proof of principle' in a peripheral model that retinoids are potential therapeutic agents in ASD.
    FEBS letters 06/2011; 585(11):1529-36. DOI:10.1016/j.febslet.2011.05.004 · 3.34 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We used a bioluminescence resonance energy transfer biosensor to screen for functional selective ligands of the human oxytocin (OT) receptor. We demonstrated that OT promoted the direct engagement and activation of G(q) and all the G(i/o) subtypes at the OT receptor. Other peptidic analogues, chosen because of specific substitutions in key OT structural/functional residues, all showed biased activation of G protein subtypes. No ligand, except OT, activated G(oA) or G(oB), and, with only one exception, all of the peptides that activated G(q) also activated G(i2) and G(i3) but not G(i1), G(oA), or G(oB), indicating a strong bias toward these subunits. Two peptides (DNalOVT and atosiban) activated only G(i1) or G(i3), failed to recruit β-arrestins, and did not induce receptor internalization, providing the first clear examples of ligands differentiating individual G(i/o) family members. Both analogs inhibited cell proliferation, showing that a single G(i) subtype-mediated pathway is sufficient to prompt this physiological response. These analogs represent unique tools for examining the contribution of G(i/o) members in complex biological responses and open the way to the development of drugs with peculiar selectivity profiles. This is of particular relevance because OT has been shown to improve symptoms in neurodevelopmental and psychiatric disorders characterized by abnormal social behaviors, such as autism. Functional selective ligands, activating a specific G protein signaling pathway, may possess a higher efficacy and specificity on OT-based therapeutics.
    Journal of Biological Chemistry 11/2011; 287(6):3617-29. DOI:10.1074/jbc.M111.277178 · 4.60 Impact Factor