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：新的精神障碍诊断的高峰发生率在男性为15至19岁，在男性为20至24岁。 妇女然而，妇女也表现出第二个发病率高峰和对疾病的脆弱性， 40多岁和50出头。人们提出了一些理论来解释这第二个高峰，包括呼吁 雌激素和其他生殖激素的神经保护作用，这些作用在前几年减弱 绝经尽管有这些观察结果和理论基础，但几乎没有证据可以识别风险 更年期妇女精神病发展的因素。这部分是因为 在这一人群中，精神病的发展相对罕见，因此难以观察。响应于 NIMH的资助机会公告题为“在治疗期间的情绪和精神病症状”， 更年期过渡”，我们提出了一个双管齐下的方法来确定发展的风险因素 更年期过渡期的精神病我们的第一个目标是，我们建议从本地有实力的人士中招聘 179名在绝经期首次出现精神病的人 过渡，并回顾性地确定医疗，生殖，精神病和家族史的元素， 与144名发生精神病的匹配对照组相比， 抑郁症在同一时期我们假设在更年期出现精神病的女性 过渡期将报告一个前驱期的减弱症状之前，发展弗兰克 精神病，一般诱发精神病发作的因素将在 精神病队列，并且与激素波动相关的精神疾病在两个队列中都将增加 相对于人口比例。在我们的第二个目标中，我们建议利用我们团队的既定专业知识， 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妇女， 会增加他们患精神病的风险从现有的来源，我们将确定196名妇女谁是在 在更年期过渡的最早阶段，精神病的临床高风险。我们将遵循这些 女性和98名匹配的健康对照者在2年内，收集临床，行为，计算， 内分泌学和（在探索性子集中）成像和电生理学数据，因为它们过渡到 绝经我们假设基线精神病和认知症状的严重程度将预测转换为 精神病，这些症状的恶化将对应于特定的临床和激素标志物 更年期过渡期我们还假设，候选精神病生物标志物将预测转换 和功能下降，并将受到更年期过渡标志物的影响。这些研究一起 将是第一个确定老年妇女精神病发展的明确危险因素。我们的目标是利用 所产生的数据用于制定具体的干预措施，以减轻这一弱势群体的精神病风险。