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

• 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
• 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

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障碍通常被认为是青春期和早期的障碍 成年期：新诊断的精神障碍发病率最高的是男性15至19岁和20至24岁。 女人。然而，妇女也表现出发病率的第二个高峰和对疾病的脆弱性。 40多岁和50岁出头。已经提出了解释第二个高峰的理论，包括向 雌激素和其他生殖激素的神经保护作用，在前几年逐渐减弱 更年期。尽管有这些观察和理论基础，但识别风险的证据很少。 更年期妇女精神病发展的影响因素。这部分是因为 在这个人群中，精神病的发展相对罕见，因此很难观察到。作为对.的回应 NIMH基金机会公告，题为《情绪和精神病症状在 更年期“，我们提出了一种双管齐下的方法来确定发展的风险因素。 更年期过渡期间的精神错乱。在我们的第一个目标中，我们建议从现有的本地员工中招聘 国家资料来源：179名绝经期首发精神病患者 并回顾确定病史、生殖病史、精神病史和家族史中 与144名匹配的对照组相比，易患精神病的人 同一时期的抑郁症。我们假设在更年期发展成精神病的女性 过渡期将报告在弗兰克发展之前症状减弱的前驱时期。 精神病，一般易患精神病的因素在 精神疾病队列，与激素波动有关的精神障碍将在两个队列中升高 相对于人口比率。在我们的第二个目标中，我们建议利用我们团队在以下方面的成熟专业知识 确定精神病的风险因素以前瞻性地研究已减轻精神病症状的女性， 增加他们患精神病的风险。从确定的来源中，我们将确定196名女性 在绝经过渡的早期阶段，精神病的临床风险很高。然后我们将遵循这些 女性和98名健康对照组在两年多的时间里，收集了临床、行为、计算、 内分泌学，以及(在探索性子集中)成像和电生理数据 更年期。我们假设，基线精神病和认知症状严重程度将预测转化为 精神病和这些症状的恶化将与特定的临床和激素标志相对应 更年期的转变。我们还假设候选精神病生物标记物将预测转化 和功能下降，并将受到更年期转变的标志的影响。总而言之，这些研究 将是第一个确定老年女性精神病发展的明确风险因素。我们的目标是利用 产生的数据用于制定具体的干预措施，以减轻这一脆弱人群中的精神病风险。