Background-Emerging evidence from clinical trials suggests that oral estrogen and intranasal oxytocin might reduce symptom severity in schizophrenia. Whether increases in endogenous hormones are similarly associated with improved symptoms is unknown. We investigated the effects of menstrual cycle phase and related fluctuations in peripheral hormone levels on clinical symptoms in women with chronic schizophrenia.Method-Twenty-three women with schizophrenia were administered the Positive and Negative Syndrome Scale (PANSS), a measure of clinical symptom severity, at two menstrual cycle phases: 1) early follicular (Days 2-4; low estrogen/progesterone) and 2) midluteal (Days 20-22; high estrogen/progesterone). Twenty-seven males with schizophrenia and 58 controls (31 female) completed testing at comparable intervals. Men were included to examine whether the relationships between clinical symptoms and hormone levels in women generalize to men. Plasma hormone assays of estrogen, oxytocin, progesterone, and testosterone were obtained.Results-Female patients showed less severe symptoms during the midluteal versus early follicular phase (p's<0.01). Oxytocin did not fluctuate across phases, but in female patients (p's<0.01) higher oxytocin levels were associated with less severe positive symptoms and overall psychopathology. In both sexes, higher oxytocin levels were associated with more prosocial behaviors (p<0.05).Requests for reprints and correspondences should be addressed to: Leah H. Rubin, Ph.D., University of Illinois at Chicago, Department of Psychiatry, 912 S. Wood St. (MC 913), Chicago, Illinois 60612, (312) 355-5017 (phone), (312) 413-7856 (fax), lrubin@psych.uic.edu. Contributors Drs. Rubin and Maki conceived the idea and methodology for the study. Dr. Carter developed the methodology to explore oxytocin and served as an advisor and resource on this project for understanding oxytocin. Dr. Sweeney served as an advisor on this project and provided his expertise in schizophrenia. Dr. Pournajafi-Nazarloo and Ms. Drogos ran the oxytocin assays. Dr. Rubin, Dr. Maki's lab, and the Center for Cognitive Medicine were involved in recruitment and clinical assessments. Dr. Rubin conducted the statistical analyses and wrote the first draft. Drs. Rubin, Maki, Carter, and Sweeney exchanged multiple versions of the manuscript. All authors contributed to the writing of the manuscript and approval of the final version. Conflict of interestDr. Sweeney is a consultant to Pfizer and has a research grant from Janssen. Dr. Maki received honoraria from the American Nutraceutical Association and research support from the Soy Health Research Program. All other authors declare that, except for income received from their primary employer, no financial support or compensation has been received from any individual or corporate entity over the past 3 years for research or professional service, and there are no personal financial holdings that could be perceived as constituting a potential conflict of interest.Publisher's Disclaimer:...

SummaryAnimal studies have implicated oxytocin and vasopressin in social bonding, physiological stress responses, and wound healing. In humans, endogenous oxytocin and vasopressin levels covary with perceptions of relationship quality, marital behaviors, and physiological stress responses. To investigate relationships among marital behavior, oxytocin, vasopressin, and wound healing, and to determine the characteristics of individuals with the highest neuropeptide levels, 37 couples were admitted for a 24-hour visit in a hospital research unit. After small blister wounds were created on their forearm, couples participated in a structured social support interaction task. Blister sites were monitored daily following discharge to assess wound repair speed. Blood samples were collected for oxytocin, vasopressin, and cytokine analyses. Higher oxytocin levels were associated with more positive communication behaviors during the structured interaction task. Furthermore, individuals in the upper oxytocin quartile healed blister wounds faster than participants in lower oxytocin quartiles. Higher vasopressin levels were related to fewer negative communication behaviors and greater tumor necrosis factor-α production. Moreover, women in the upper vasopressin quartile healed the experimental wounds faster than the remainder of the sample. These data confirm and extend prior evidence implicating oxytocin and vasopressin in couples' positive and negative communication behaviors, and also provide further evidence of their role in an important health outcome, wound healing.

Background In women with chronic schizophrenia, higher levels of peripheral oxytocin have been associated with lower levels of positive but not negative symptoms. Sex-specific associations between endogenous levels of oxytocin (OT) and arginine-vasopressin (AVP) with clinical symptoms and cognition in untreated early course patients have not been examined. Method Clinical ratings and neuropsychological testing were performed in thirty-eight acutely ill, unmedicated first-episode schizophrenia patients (14 women, 24 men). Serum hormone assays were obtained in patients and thirty-eight demographically similar healthy controls. Results Patients demonstrated increased AVP levels compared to controls (p=0.01). Higher AVP levels were associated with greater positive symptoms (r=0.58, p=0.03) and worse verbal learning (r=−0.63, p=0.02) in female, but not male, patients. OT levels did not statistically differ between patients and controls, and were unrelated to clinical symptoms or cognition in patients. Conclusion Results suggest an association of endogenous AVP with increased positive symptom severity and worse cognition in untreated female, but not male, schizophrenia patients. Findings support the role of neuroendocrine alterations in acute psychosis and the importance of examining sex-specific neuroendocrine alterations early in the course of schizophrenia.

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