Effects of Estrogen on Cognition in Schizophrenia

描述(由申请者提供)：本申请申请资助一个有指导的博士前培训计划，该计划涉及使用心理神经内分泌研究方法来更好地了解精神分裂症的性别差异。拟议的研究培训计划的总体目标是确定导致精神分裂症认知功能变化的神经内分泌机制。这项研究的具体目的是描述雌激素水平的个体差异如何影响表现出性别差异的认知能力。该研究计划的较长期目标将是将精神神经内分泌学的教学培训和实践研究培训应用于系统调查精神分裂症的性别差异。患有精神分裂症的女性雌激素水平降低，雌激素的变化会影响认知过程(例如，言语记忆、视觉空间能力)，而这些认知过程在疾病中是受损的。在这项拟议的研究中，我们将使用非侵入性月经周期范例来检验内源性雌激素对精神分裂症患者认知的影响。60名正常骑车的女性(30名健康女性和30名患者)将在月经周期的两个时间点完成一系列神经心理测试。检测将在卵泡早期(低雌激素和黄体酮；第2-4天)和黄体中期(高激素；第21-25天)进行。测试之间的间隔时间约为1.5个月(即在两个单独的周期内)。我们还将在第一次治疗和1.5个月后的两个时间点上检查30名患有精神分裂症的男性和30名非精神分裂症男性的认知功能。我们假设，当雌激素水平较高而雌激素水平较低时，患有精神分裂症的女性将在临床症状、视觉扫描和精细运动技能方面有所改善，而在视觉空间能力方面表现较差，并且这些变化将与雌二醇的变化相关。相反，我们预测，与早期卵泡期相比，语言能力，包括语言流畅性和语言记忆力，在黄体中期将会下降，这些影响将与黄体酮的变化相关。这些结果将为这一领域的更大规模的研究计划奠定基础，方法是确定精神分裂症患者性别二态认知能力(男性或女性表现出优势的能力)的性别差异，并证明这些领域的缺陷随着月经周期中内源性激素水平的不同而不同。这项新的工作可以为雌激素和孕激素在调节精神分裂症症状和认知方面的潜在调节作用提供新的见解，并指导开发新的内分泌干预措施，以减少作为精神分裂症残疾的主要原因的治疗抵抗性认知障碍。

DESCRIPTION (provided by applicant): This application requests funding for a mentored predoctoral training program involving the use of psychoneuroendocrine research methods to better understand sex differences in schizophrenia. The general aim of the proposed research training program is to identify neuroendocrine mechanisms that contribute to variations in cognitive function in schizophrenia. The specific aims of the research are to characterize how individual variation in estrogen levels affects cognitive abilities that show a sex difference. The longer-term objective of the research program will be to apply didactic training in psychoneuroendocrinology and hands-on research training to the systematic investigation of sex differences in schizophrenia. Women with schizophrenia have decreased levels of estrogen, and variations in estrogen affects cognitive processes (e.g., verbal memory, visuospatial abilities) that are impaired in the disease. In the proposed study we will examine the effects of endogenous estrogen on cognition in schizophrenia using a non-invasive menstrual cycle paradigm. Sixty normally cycling women (30 healthy and 30 patients) will complete a battery of neuropsychological tests at two points in the menstrual cycle. Testing will occur at the early follicular (low estrogen and progesterone; days 2-4) phase and the midluteal (high hormones; days 21- 25) phase. Time between testing will be approximately 1.5-months (i.e., during two separate cycles). We will also examine cognitive function in 30 men with and 30 without schizophrenia at two points in time, at the first session and 1.5-months later. We hypothesize that women with schizophrenia will show improvements in clinical symptoms, visual scanning, and fine motor skills and perform worse on visuospatial abilities when estrogen levels are high compared to low levels of estrogen, and that these changes will correlate with changes in estradiol. Conversely, we predict that verbal abilities, including verbal fluency and verbal memory, will decrease during the midluteal compared to early follicular phase, and that these effects will correlate with changes in progesterone. These results will lay the foundation for a larger research program in this area by establishing sex differences in sexually dimorphic cognitive abilities (abilities where men or women show an advantage) in schizophrenia, and by demonstrating that deficits in these domains vary with endogenous hormone levels over the menstrual cycle. This new line of work can provide new insights into the potential modulatory effects of estrogen and progesterone in mediating symptoms and cognition in schizophrenia, and guide development of novel endocrine interventions to reduce the treatment resistant cognitive impairments that are a major cause of disability in schizophrenia.