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:...

Objective: To examine sex differences in the relationship between clinical symptoms related to Alzheimer disease (AD) (verbal memory deficits) and neurodegeneration (hippocampal volume/ intracranial volume ratio [HpVR]) across AD stages. Methods:The sample included 379 healthy participants, 694 participants with amnestic mild cognitive impairment (aMCI), and 235 participants with AD and dementia from the Alzheimer's Disease Neuroimaging Initiative who completed the Rey Auditory Verbal Learning Test (RAVLT). Cross-sectional analyses were conducted using linear regression to examine the interaction between sex and HpVR on RAVLT across and within diagnostic groups adjusting for age, education, and APOE e4 status.Results: Across groups, there were significant sex 3 HpVR interactions for immediate and delayed recall (p , 0.01). Women outperformed men among individuals with moderate to larger HpVR, but not among individuals with smaller HpVR. In diagnosis-stratified analyses, the HpVR 3 sex interaction was significant in the aMCI group, but not in the control or AD dementia groups, for immediate and delayed recall (p , 0.01). Among controls, women outperformed men on both outcomes irrespective of HpVR (p , 0.001). In AD dementia, better RAVLT performance was independently associated with female sex (immediate, p 5 0.04) and larger HpVR (delayed, p 5 0.001). The cognitive reserve theory posits that favorable premorbid factors including higher education and IQ delay the onset of clinical deficits despite Alzheimer disease (AD)-related neurodegeneration because compensatory mechanisms are more readily engaged (e.g., alternate brain networks or cognitive strategies). Conclusion:1-3 The theory predicts that the onset of accelerated cognitive decline is closer in time to AD dementia diagnosis in individuals with greater cognitive reserve; however, after onset, their decline is more rapid because neurodegeneration is more advanced at that point. [4][5][6] Throughout life, women outperform men on verbal memory tasks. [7][8][9] We predict that this female advantage may reflect a sex-specific form of cognitive reserve resulting in a delay in the clinical manifestation of memory impairment until more advanced neurodegeneration overwhelms the female advantage and decline begins. Thereafter, we predict that women decline From the Einstein Aging Study and the