Trajectories of Aging in Psychotic Disorders Over 27 Years

27 年来精神障碍的衰老轨迹

• 批准号: 9767279
• 负责人: Roman I Kotov
• 金额: $ 73.74万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-19 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9767279
• 关键词: Address; Admission activity; Age; Aging; Apolipoprotein E; Back; Biological; Biological Assay; Biological Markers; Biological Process; Bipolar Disorder; Blood Tests; Blood specimen; Caring; Cognition; Cognitive; County; Data; Data Analyses; Deterioration; Diabetes Mellitus; Diet; Disease; Equilibrium; Evaluation; Event-Related Potentials; Exposure to; Functional disorder; General Population; Genetic; Genetic Risk; Genotype; Geography; Hand Strength; Health; Health Promotion; Heart Diseases; Hydrocortisone; Hypertension; Impaired cognition; Impairment; Inflammation; Intervention; Lead; Life; Life Expectancy; Longevity; Longitudinal Studies; Longterm Follow-up; Maps; Mediating; Medical; Medical History; Mental Health; Metabolic; Metabolic Marker; Metabolic syndrome; Modeling; Mood Disorders; Morbidity - disease rate; National Institute of Mental Health; Neurodevelopmental Disorder; Neuronal Dysfunction; Obesity; Outcome; Participant; Patients; Pattern; Persons; Phase; Physical Function; Physical Performance; Physical activity; Physiological; Population; Poverty; Premature Mortality; Premature aging syndrome; Prevalence; Prevention; Preventive Intervention; Psychotic Disorders; Research; Research Design; Risk; Risk Factors; Schizophrenia; Smoking; Strategic Planning; Survivors; Testing; Time; age difference; age related; allostatic load; cognitive function; cognitive testing; cohort; comparison group; design; epidemiology study; experience; frailty; hazard; hypothalamic-pituitary-adrenal axis; improved; innovation; modifiable risk; mortality; neural patterning; neuron loss; older patient; performance tests; population health; premature; prospective test; relating to nervous system; severe mental illness; virtual

Life expectancy is approximately 20 years shorter in schizophrenia and 10 years shorter in mood disorder with psychosis than in the general population, which is almost entirely due to natural-cause mortality. One proposed explanation is that psychotic disorders are associated with accelerated aging. Substantial evidence indicates that this population experiences premature declines in three functional domains: internal (i.e., age- related medical disorders), cognitive, and physical. However, it is unknown whether these declines are explainable by exposure to risk factors highly elevated in psychotic disorders (obesity, poverty, smoking, low physical activity, poor diet, inadequate medical care, etc) or are also due to pathophysiology of psychosis itself. Indeed, biological processes associated with psychosis—genetic, neural (P3 and mismatch negativity), and allostatic load (metabolic problems, increased inflammation, hypothalamic-pituitary-adrenal axis dysregulation, and hypertension)—were found to predict accelerated aging in the general population, but this has not been tested in psychotic disorders. Moreover, it remains uncertain when accelerated aging starts and how rapidly it progresses, as prior studies typically began with older patients. Prevention of premature aging in psychotic disorders would extend life and improve health of millions of people, but it is unclear how to target such efforts, because fundamental information is lacking on trajectories of aging and their determinants in psychosis. The Suffolk County Mental Health Project (SCMHP; MH094398) offers a unique opportunity to fill these crucial gaps. It is the only US epidemiologic study designed to examine health, cognition, and physical performance in psychotic disorders over 27 years following first admission (from mean age 30 to 57). In addition, the study has gathered a wealth of information on premorbid risk factors. It also includes a geographically and demographically matched never-psychotic comparison group. Thorough assessments of cases were done 6 times during the first two decades. At Year 20 (mean age 49), both case (N=385) and never-psychotic (N=261) groups completed a comprehensive psychiatric evaluation, medical history, physical performance tests, anthropometric exam, cognitive testing, event-related potentials battery, assays of blood samples, and genotyping. The present proposal is to reassess cases and never-psychotic participants at ages 54 and 57 to trace divergence of aging trajectories during a pivotal period (age 49 to 57, when medical morbidity is expected to double and cognitive and physical functioning begin to decline) and identify risk factors and biological vulnerabilities that help to determine what path aging takes. This innovative design will enable us to clarify when and why aging is accelerated in psychotic disorders, and where interventions can be applied most productively to extend life expectancy and health of this population.

精神分裂症患者的预期寿命大约缩短20岁，心境障碍患者的预期寿命缩短10年 精神病的发病率高于普通人群，这几乎完全是自然原因造成的死亡。一 提出的解释是，精神障碍与加速衰老有关。确凿的证据 表明这一群体在三个功能领域经历了过早的下降：内部(即，年龄- 相关的医学障碍)、认知和身体障碍。然而，目前还不清楚这些下降是否是 可通过暴露于精神障碍(肥胖、贫困、吸烟、低血压)中高度升高的风险因素来解释 体力活动、不良饮食、医疗护理不足等)，或者也是由于精神病本身的病理生理学。 事实上，与精神病相关的生物过程--遗传、神经(P3和失配负性)，以及 不平衡负荷(代谢问题、炎症增加、下丘脑-垂体-肾上腺轴失调、 和高血压)--被发现可以预测普通人群的加速衰老，但这还没有 精神错乱的测试。此外，老龄化加速开始的时间和速度仍不确定 进展，因为以前的研究通常是从老年患者开始的。精神病患者过早衰老的预防 疾病将延长数百万人的寿命并改善他们的健康，但目前还不清楚如何针对这些努力， 因为缺乏关于衰老轨迹及其在精神病中的决定因素的基本信息。这个 萨福克县精神卫生项目(SCMHP；MH094398)提供了一个独特的机会来填补这些关键的 差距。这是美国唯一一项旨在检查健康、认知和身体表现的流行病学研究 首次入院后27年以上的精神障碍(平均年龄30至57岁)。此外，这项研究还 收集了大量有关发病前风险因素的信息。它还包括一个地理上和 在人口学上匹配的非精神病对照组。对病例进行了彻底的评估6 在最初的二十年里。在20岁时(平均年龄49岁)，病例(N=385)和非精神病患者(N=261) 小组完成了全面的精神评估，病史，体能测试， 人体测量检查，认知测试，事件相关电位组合，血液样本分析，以及 基因分型。目前的建议是重新评估54岁和57岁的病例和从未患精神病的参与者到 在一个关键时期(49岁至57岁，预计会有医疗发病率)衰老轨迹的踪迹差异 加倍，认知和身体功能开始下降)，并确定风险因素和生物学 有助于确定老化路径的漏洞。这一创新的设计将使我们能够澄清 精神病患者衰老加速的时间和原因，以及在哪里可以进行最多的干预 有效地延长这一人群的预期寿命和健康。