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Schizophr Bull. 2019 Oct 9. pii: sbz091. doi: 10.1093/schbul/sbz091. [Epub ahead of print]

Oxytocin Enhances an Amygdala Circuit Associated With Negative Symptoms in Schizophrenia: A Single-Dose, Placebo-Controlled, Crossover, Randomized Control Trial.

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Sierra Pacific Mental Illness Research Education and Clinical Centers, San Francisco VA Medical Center, and the University of California, San Francisco, CA.
Mental Health Service, San Francisco Veterans Affairs Medical Center, San Francisco, CA.
Department of Psychiatry, University of California San Francisco, San Francisco, CA.
Department of Computer Science, Universidad Carlos III de Madrid, Madrid, Spain.
Department of Psychiatry, University of Minnesota, Minneapolis, MN.
Clinical Translational Neuroscience Laboratory, Department of Psychiatry and Human Behavior, University of California Irvine, Irvine, CA, USA.
The Mind Research Network, Albuquerque, NM.
Department of Psychiatry, University of New Mexico, Albuquerque, NM.
Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, NM.
Department of Psychiatry and Human Behavior, University of California Irvine, Irvine, CA, USA.
Department of Psychology, Georgia State University, Atlanta, GA.


Negative symptoms are core contributors to vocational and social deficits in schizophrenia (SZ). Available antipsychotic medications typically fail to reduce these symptoms. The neurohormone oxytocin (OT) is a promising treatment for negative symptoms, given its role in complex social behaviors mediated by the amygdala. In sample 1, we used a double-blind, placebo-controlled, crossover design to test the effects of a single dose of intranasal OT on amygdala resting-state functional connectivity (rsFC) in SZ (n = 22) and healthy controls (HC, n = 24) using a whole-brain corrected approach: we identified regions for which OT modulated SZ amygdala rsFC, assessed whether OT-modulated circuits were abnormal in SZ relative to HC on placebo, and evaluated whether connectivity on placebo and OT-induced connectivity changes correlated with baseline negative symptoms in SZ. Given our modest sample size, we used a second SZ (n = 183) and HC (n = 178) sample to replicate any symptom correlations. In sample 1, OT increased rsFC between the amygdala and left middle temporal gyrus, superior temporal sulcus, and angular gyrus (MTG/STS/AngG) in SZ compared to HC. Further, SZ had hypo-connectivity in this circuit compared to HC on placebo. More severe negative symptoms correlated with less amygdala-to-left-MTG/STS/AngG connectivity on placebo and with greater OT-induced connectivity increases. In sample 2, we replicated the correlation between amygdala-left-MTG/STS/AngG hypo-connectivity and negative symptoms, finding a specific association with expressive negative symptoms. These data suggest intranasal OT can normalize functional connectivity in an amygdala-to-left-MTG/STS/AngG circuit that contributes to negative symptoms in SZ.


expressive negative symptoms; functional connectivity; resting-state; temporal lobe


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