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The Journal of Neuroscience, December 7, 2005, 25(49):11489-11493; doi:10.1523/JNEUROSCI.3984-05.2005

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BRIEF COMMUNICATION
Oxytocin Modulates Neural Circuitry for Social Cognition and Fear in Humans

Peter Kirsch,¹ Christine Esslinger,¹ Qiang Chen,^2,4 Daniela Mier,¹ Stefanie Lis,¹ Sarina Siddhanti,^3,4 Harald Gruppe,¹ Venkata S. Mattay,^2,4 Bernd Gallhofer,¹ and Andreas Meyer-Lindenberg^2,3,4

¹Cognitive Neuroscience Group, Center for Psychiatry and Psychotherapy, Justus-Liebig University, D-35385 Giessen, Germany, and ²Neuroimaging Core Facility, ³Unit for Systems Neuroscience in Psychiatry, and ⁴Clinical Brain Disorders Branch, Genes, Cognition, and Psychosis Program, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892

In non-human mammals, the neuropeptide oxytocin is a key mediator of complex emotional and social behaviors, including attachment, social recognition, and aggression. Oxytocin reduces anxiety and impacts on fear conditioning and extinction. Recently, oxytocin administration in humans was shown to increase trust, suggesting involvement of the amygdala, a central component of the neurocircuitry of fear and social cognition that has been linked to trust and highly expresses oxytocin receptors in many mammals. However, no human data on the effects of this peptide on brain function were available. Here, we show that human amygdala function is strongly modulated by oxytocin. We used functional magnetic resonance imaging to image amygdala activation by fear-inducing visual stimuli in 15 healthy males after double-blind crossover intranasal application of placebo or oxytocin. Compared with placebo, oxytocin potently reduced activation of the amygdala and reduced coupling of the amygdala to brainstem regions implicated in autonomic and behavioral manifestations of fear. Our results indicate a neural mechanism for the effects of oxytocin in social cognition in the human brain and provide a methodology and rationale for exploring therapeutic strategies in disorders in which abnormal amygdala function has been implicated, such as social phobia or autism.

Key words: amygdala; social cognition; human; fMRI; oxytocin; fear

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Received Sep 12, 2005; revised October 30, 2005; accepted November 6, 2005.

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