Leah H Rubin1, Siyi Li2, Li Yao2, Sarah K Keedy3, James L Reilly4, Scot K Hill5, Jeffrey R Bishop6, C Sue Carter7, Hossein Pournajafi-Nazarloo7, Lauren L Drogos8, Elliot Gershon3, Godfrey D Pearlson9, Carol A Tamminga10, Brett A Clementz11, Matcheri S Keshavan12, Su Lui13, John A Sweeney14. 1. Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, United States of America; Departments of Neurology and Epidemiology, Johns Hopkins University, Baltimore, MD, United States of America. 2. Department of Radiology, West China Hospital of Sichuan University, Chengdu, People's Republic of China. 3. Department of Psychiatry, University of Chicago, Chicago, IL, United States of America. 4. Department of Psychiatry and Behavioral Sciences, Northwestern University, Chicago, IL, United States of America. 5. Department of Psychology, Rosalind Franklin University of Medicine and Science, North Chicago, IL, United States of America. 6. Departments of Pharmacy and Psychiatry, University of Minnesota, Minneapolis, MN, United States of America. 7. Kinsey Institute, Bloomington, IN, United States of America. 8. Departments of Physiology and Pharmacology, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada. 9. Departments of Psychiatry and Neurobiology, Yale University and Olin Neuropsychiatric Research Center, Hartford, CT, United States of America. 10. Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, United States of America. 11. Department of Psychology, University of Georgia, Athens, GA, United States of America. 12. Department of Psychiatry, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, United States of America. 13. Department of Radiology, West China Hospital of Sichuan University, Chengdu, People's Republic of China. Electronic address: lusuwcums@hotmail.com. 14. Department of Radiology, West China Hospital of Sichuan University, Chengdu, People's Republic of China; Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, United States of America; Department of Psychiatry, University of Cincinnati, United States of America.
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.
BACKGROUND:Oxytocin (OT) and argininevasopressin (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 schizophreniapatients. 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.
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