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; 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病疾病通常被认为是青少年和早期的疾病 成年：新精神病诊断的峰值发病率是男性的15到19，在20到24中。 女性。但是，妇女还表现出第二个事件的高峰和疾病的脆弱性 40年代和50年代初。已经提出了理论来解释第二个峰，包括出现在 雌激素和其他生殖激素的神经保护作用，在此之前的几年中减弱 绝经。尽管有这些观察和理论基础，但几乎没有证据来确定风险 经历更年期过渡的女性精神病发展的因素。这部分是因为 该人群中精神病的发展相对较少，因此很难观察到。响应 NIMH资助机会公告的标题为“情绪和精神病症状 更年期过渡”，我们提出了一种两方的方法来识别发展风险因素 更年期过渡期间的精神病。在我们的第一个目标中，我们建议从既定的本地招募 国家消息来源179个人在更年期期间发展了第一集的精神病 过渡并追溯确定医学，复制，精神病和家族史的要素 与开发的144个匹配的对照相比，精神病的发展倾向 同一时期的抑郁症。我们假设在更年期期间发展精神病的女性 过渡将报告弗兰克（Frank）发展之前的衰减符号的前驱时期 精神病，这些因素通常会诱发精神病的发作，将相对代表 精神病队列以及与激素波动相关的精神疾病将在这两个队列中升高 相对于人口率。在我们的第二个目标中，我们建议利用团队既定的专业知识 确定精神病的危险因素，以研究衰减精神病症状的女性， 提高他们患精神病的风险。从既定来源，我们将确定196位在 在更年期过渡的最早阶段，精神病的临床高风险。然后我们将遵循这些 妇女和98个在2年内匹配健康对照，收集临床，行为，计算， 内分泌学，（在探索性子集中）成像和电生理数据向 绝经。我们假设基线精神病和认知症状严重程度将预测转换为 精神病和这些症状的恶化将对应于特定的临床和激素标记 更年期过渡。我们还假设候选精神病生物标志物将预测转化 和功能下降，并将受到更年期过渡的标记的影响。在一起，这些研究 将是第一个确定衰老女性精神病发展的确定风险因素的人。我们的目标是使用 生成的数据是为了开发特定的干预措施，以减轻该脆弱人群的精神病风险。