PREMAP - Predictors and Risk Evaluation for Menopause-Associated Psychosis

PREMAP - 更年期相关精神病的预测因素和风险评估

基本信息

批准号：
10567665
负责人：
Albert R Powers
金额：
$ 82.27万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-01-18 至 2027-10-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10567665
关键词：
Admission activity Adolescence Age Aging Applications Grants Attenuated Behavioral Belief Biological Markers Clinical Data Development Diagnosis Disease Early identification Early treatment Electrophysiology (science)Elements Endocrinology Epidemiology Estradiol Estrogen decline Estrogens Evaluation Exhibits Family Funding Opportunities Future Gender Goals Hormonal Hormones Image Incidence Individual Intervention Interview Life Longevity Medical Medical History Menopause Menstrual cycle Mental Depression Mental disorders Moods National Institute of Mental Health Neurobehavioral Manifestations Neurobiology Outcome Participant Performance Perimenopause Persons Phase Placebos Population Postpartum Depression Postpartum Period Predisposing Factor Pregnancy Premature Menopause Progesterone Prospective Studies Psychoses Psychotic Disorders Randomized, Controlled Trials Recording of previous events Relative Risks Reporting Retrospective Studies Risk Risk Factors Risk Marker Schizophrenia Semantics Severities Source Structure Symptoms System Testing Time Study Unipolar Depression Update Vulnerable Populations Woman Work Youth attenuated psychosis syndrome behavior prediction clinical high risk for psychosis cohort comorbidity dysphoria early psychosis emerging adult experience first episode psychosis functional decline high risk improved men neural neuroprotection prospective psychosis risk psychotic symptoms recruit reproductive reproductive hormone response risk mitigation risk prediction risk stratification schizophrenia risk sex symptomatic improvement theories treatment strategy young adult

项目摘要

Schizophrenia and other psychotic disorders are typically thought of as disorders of adolescence and early adulthood: the peak incidence of new psychotic disorder diagnoses is from 15 to 19 in men and 20 to 24 in women. However, women also demonstrate a second peak of incidence and vulnerability to the illness in their 40s and early 50s. Theories have been proposed to explain this second peak, including appeals to the neuroprotective effects of estrogen and other reproductive hormones, which wane in the years preceding menopause. Despite these observations and theoretical groundwork, very little evidence exists to identify risk factors for development of psychosis in women experiencing the menopause transition. This is partly because development of psychosis in this population is relatively rare and is thus difficult to observe. In response to the NIMH funding opportunity announcement entitled, “Mood and Psychosis Symptoms during the Menopause Transition”, we propose a two-pronged approach to identify risk factors for development of psychosis during the menopause transition. In our first aim, we propose to recruit from established local and national sources 179 individuals who have developed a first episode of psychosis during the menopause transition and to retrospectively identify elements of medical, reproductive, psychiatric, and family history that predispose to the development of psychosis when compared to 144 matched controls who developed depression in the same period. We hypothesize that women who developed psychosis during the menopause transition will report a prodromal period of attenuated symptoms preceding the development of frank psychosis, that factors generally predisposing to psychosis onset will be relatively over-represented in the psychosis cohort, and that psychiatric disorders tied to hormone fluctuations will be elevated in both cohorts relative to population rates. In our second aim, we propose to leverage our team’s established expertise in identifying risk factors for psychosis to prospectively study women who have attenuated psychotic symptoms, elevating their risk for developing psychosis. From established sources, we will identify 196 women who are at clinical high risk for psychosis during the earliest phases of the menopause transition. We will then follow these women and 98 matched healthy controls over 2 years, collecting clinical, behavioral, computational, endocrinological, and (in an exploratory subset) imaging and electrophysiological data as they transition toward menopause. We hypothesize that baseline psychotic and cognitive symptom severity will predict conversion to psychosis and that the worsening of these symptoms will correspond to specific clinical and hormonal markers of the menopause transition. We also hypothesize that candidate psychosis biomarkers will predict conversion and functional decline and will be impacted by markers of the menopause transition. Together, these studies will be the first to identify definitive risk factors for psychosis development in aging women. Our goal is to use the data generated to develop specific interventions to mitigate risk for psychosis in this vulnerable population.

精神分裂症和其他精神病通常被认为是青春期和早期的疾病成年期：男性新诊断精神障碍的发病率高峰为 15 至 19 岁，男性为 20 至 24 岁。然而，女性也表现出了第二个发病高峰，并且她们对这种疾病的脆弱性也很高。 20 世纪 40 年代和 50 年代初，人们提出了一些理论来解释第二个高峰，其中包括诉诸科学理论。雌激素和其他生殖激素的神经保护作用在前几年减弱尽管有这些观察和理论基础，但很少有证据可以确定风险。经历更年期过渡的女性出现精神病的因素部分是因为。该人群中出现精神病的情况相对较少，因此很难观察到。 NIMH 资助机会公告，题为“情绪和精神病症状更年期过渡”，我们提出了一种双管齐下的方法来确定发展的风险因素在我们的第一个目标中，我们建议从当地已建立的机构中招募人员。和国家来源的 179 名在更年期期间出现首次精神病发作的人转变并回顾性地识别医学、生殖、精神病学和家族史的要素与 144 名患有精神病的匹配对照者相比，他们更容易患上精神病我们与在同一时期患上抑郁症的女性作斗争。过渡期将报告在发展为坦率之前症状减轻的前驱期。精神病，通常诱发精神病发作的因素在精神病队列，并且与激素波动相关的精神疾病在这两个队列中都会升高相对于人口率，我们建议利用我们团队在以下方面的既定专业知识。确定精神病的危险因素，以前瞻性地研究精神病症状减轻的女性，增加她们患精神病的风险从现有来源中，我们将确定 196 名处于这种状态的女性。在绝经过渡的最早阶段，我们将跟踪这些临床精神病的高风险。女性和 98 名匹配的健康对照在 2 年内收集了临床、行为、计算、内分泌学，以及（在探索性子集中）成像和电生理学数据，因为它们过渡到我们追求基线精神病和认知症状的严重程度可以预测更年期的转变。精神病，这些症状的恶化将与特定的临床和激素标志物相对应我们还发现候选精神病生物标志物将预测转变。和功能衰退，并将受到更年期过渡标志物的影响。将是第一个确定老年女性精神病发展的明确危险因素的人。生成的数据用于制定具体干预措施，以减轻这一弱势群体患精神病的风险。