Peripheral oxytocin and vasopressin modulates regional brain activity differently in men and women with schizophrenia

Leah H. Rubin, Siyi Li, Li Yao, Sarah K. Keedy, James L. Reilly, Scot K. Hill, Jeffrey R. Bishop, C. Sue Carter, Hossein Pournajafi-Nazarloo, Lauren L. Drogos, Elliot Gershon, Godfrey D. Pearlson, Carol A. Tamminga, Brett A. Clementz, Matcheri S. Keshavan, Su Lui*, John A. Sweeney

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Background: Oxytocin (OT) and arginine vasopressin (AVP) exert sexually dimorphic effects on cognition and emotion processing. Abnormalities in these hormones are observed in schizophrenia and may contribute to multiple established sex differences associated with the disorder. Here we examined sex-dependent hormone associations with resting brain activity and their clinical associations in schizophrenia patients. Methods: OT and AVP serum concentrations were assayed in 35 individuals with schizophrenia (23 men) and 60 controls (24 men) from the Chicago BSNIP study site. Regional cerebral function was assessed with resting state fMRI by measuring the amplitude of low-frequency fluctuations (ALFF) which are believed to reflect intrinsic spontaneous neuronal activity. Results: In female patients, lower OT levels were associated with lower ALFF in frontal and cerebellar cortices (p's < 0.05) and in female controls AVP levels were inversely associated with ALFF in the frontal cortex (p = 0.01). In male patients, lower OT levels were associated with lower ALFF in the posterior cingulate and lower AVP levels were associated with lower ALFF in frontal cortex (p's < 0.05). In male controls, lower OT levels were associated with lower ALFF in frontal cortex and higher ALFF in the thalamus (p's < 0.05). There were some inverse ALFF-behavior associations in patients. Conclusions: Alterations in peripheral hormone levels are associated with resting brain physiology in a sex-dependent manner in schizophrenia. These effects may contribute to sex differences in psychiatric symptom severity and course of illness in schizophrenia.

Original languageEnglish (US)
Pages (from-to)173-179
Number of pages7
JournalSchizophrenia Research
Volume202
DOIs
StatePublished - Dec 2018

Funding

This work was supported in part by a 2012 NARSAD Young Investigator Grant from the Brain and Behavior Research Foundation to Dr. Rubin, and by the National Institute of Health ( K12HD055892 , K08MH083888 , MH083126 , MH077851 , MH078113 , MH077945 , MH077852 , and MH077862 ), the National Natural Science Foundation of China (Grant No. 81371527 ), and the Program for Changjiang Scholars and Innovative Research Team in Universities of China . Dr. Tamminga reports the following financial disclosures: American Psychiatric Association, Deputy Editor; Astellas, Ad Hoc Consultant; Autifony, Ad Hoc Consultant; Intra-cellular Therapies (ITI), Advisory Board, drug development; Pfizer, Ad Hoc Consultant; Sunovion, Investigator Initiated grant funding. Investigator Initiated grant funding. The remaining authors declare no conflict of interest. This work was supported in part by a 2012 NARSAD Young Investigator Grant from the Brain and Behavior Research Foundation to Dr. Rubin, and by the National Institute of Health (K12HD055892, K08MH083888, MH083126, MH077851, MH078113, MH077945, MH077852, and MH077862), the National Natural Science Foundation of China (Grant No. 81371527), and the Program for Changjiang Scholars and Innovative Research Team in Universities of China.

Keywords

  • Functional MRI
  • Oxytocin
  • Resting state
  • Schizophrenia
  • Sex differences
  • Vasopressin

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

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