There is a growing body of evidence suggesting that intranasal (IN) OT modulates social cognitive processes and behaviors in humans, including increasing gaze to eye regions of others, enhancing the ability to infer the emotions of others, and increasing face recognition memory, and socially reinforced learning. These findings are remarkably consistent with rodent studies showing that OT facilitates social recognition and the formation of social bonds. The overarching hypothesis of this Conte Center application is that OT acts in animals and human subjects to increase the salience and reinforcing value of social stimuli. These findings and our overarching hypothesis have tremendous implications for the development of novel therapies for improving social function in psychiatric disorders characterized by impaired social cognition, including autism spectrum disorder (ASD) and schizophrenia. Indeed, IN-OT enhances some aspects of social functioning in patients with ASD, including increased eye-contact, improved emotion recognition and adaptive cooperation. Despite the remarkable interest in IN-OT, very little is known regarding the psychological and neural mechanisms by which OT affects social functioning in humans. We hypothesize the reported effects of INOT on complex social cognition in humans reflects an impact on the more fundamental processes of salience and reinforcing value of social stimuli. Further we hypothesize that these effects are mediated by increased activation and functional connectivity between brain regions involved in social cue perception (e.g. amygdala) and reward (e.g. ventral striatum). We will test this hypothesis using a combined approach of social cognitive tests and functional MRI (fMRI) with IN-OT administration in healthy and ASD human subjects. We hypothesize that ASD subjects will show decreased attention to social cue and decreased responses to social reinforcers than healthy subjects. The differences will be associated with differences in neural activity and connectivity. Finally IN-OT will normalize behavioral responses and neural activity in ASD subjects. If our predictions are correct, these data will have important implications for combining IN-OT and behavioral therapies to improve social function in psychiatric disorders.

Public Health Relevance

If oxytocin is going to be used as a therapeutic for enhancing social cognition in autism, it is essential to understand how social cognition is impaired in autism, how oxytocin effects these impairments, and the brain mechanism by which oxytocin modulates social cognition. This project will examine these questions in a way that is integrative with the other Projects.

Agency
National Institute of Health (NIH)
Type
Specialized Center (P50)
Project #
5P50MH100023-02
Application #
8690161
Study Section
Special Emphasis Panel (ZMH1)
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Emory University
Department
Type
DUNS #
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Modi, Meera E; Connor-Stroud, Fawn; Landgraf, Rainer et al. (2014) Aerosolized oxytocin increases cerebrospinal fluid oxytocin in rhesus macaques. Psychoneuroendocrinology 45:49-57
Freeman, Sara M; Inoue, Kiyoshi; Smith, Aaron L et al. (2014) The neuroanatomical distribution of oxytocin receptor binding and mRNA in the male rhesus macaque (Macaca mulatta). Psychoneuroendocrinology 45:128-41
Mosher, Clayton P; Zimmerman, Prisca E; Gothard, Katalin M (2014) Neurons in the monkey amygdala detect eye contact during naturalistic social interactions. Curr Biol 24:2459-64
Freeman, S M; Walum, H; Inoue, K et al. (2014) Neuroanatomical distribution of oxytocin and vasopressin 1a receptors in the socially monogamous coppery titi monkey (Callicebus cupreus). Neuroscience 273:12-23
Rilling, James K; Young, Larry J (2014) The biology of mammalian parenting and its effect on offspring social development. Science 345:771-6
Skuse, David H; Lori, Adriana; Cubells, Joseph F et al. (2014) Common polymorphism in the oxytocin receptor gene (OXTR) is associated with human social recognition skills. Proc Natl Acad Sci U S A 111:1987-92
K├Ânig, Seth D; Buffalo, Elizabeth A (2014) A nonparametric method for detecting fixations and saccades using cluster analysis: removing the need for arbitrary thresholds. J Neurosci Methods 227:121-31