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

Samantha V. Abram, Lize De Coster, Brian J. Roach, Bryon A. Mueller, Theo G.M. Van Erp, Vince D. Calhoun, Adrian Preda, Kelvin O. Lim, Jessica A. Turner, Judith M. Ford, Daniel H. Mathalon, Joshua D. Woolley

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)661-669
Number of pages9
JournalSchizophrenia bulletin
Issue number3
StatePublished - Apr 10 2020

Bibliographical note

Funding Information:
This study was supported by a Career Development Award to Joshua Woolley (1IK2CX000758-01A1) from the Veterans Health Administration Office of Research and Development, and this work was supported by the National Center for Research Resources at the National Institutes of Health (grant numbers: NIH 1 U24 RR021992 (Function Biomedical Informatics Research Network) and NIH 1 U24 RR025736-01 (Biomedical Informatics Research Network Coordinating Center; www.birncommunity.org)). The funding sources had no role in study design, data collection, analysis, or data interpretation. Manuscript writing by S.V.A. was supported by the Department of Veterans Affairs Sierra-Pacific Mental Illness Research, Education, and Clinical Center (MIRECC).

Publisher Copyright:
© The Author(s) 2019. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.


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


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