Trajectories of Aging in Psychotic Disorders Over 27 Years

精神分裂症患者的预期寿命大约短20年，心境障碍患者短10年， 精神病患者的死亡率高于一般人群，这几乎完全是由于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。大量证据 表明该群体经历了三个功能域的过早衰退：内部（即，表示“年龄”之义 相关医学障碍）、认知和身体。然而，目前尚不清楚这些下降是否是 可解释为暴露于精神障碍中高度升高的风险因素（肥胖、贫穷、吸烟、低血糖、高血压）。 体力活动、不良饮食、医疗护理不足等）或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学过程-遗传的，神经的（P3和失配负波）， 非稳态负荷（代谢问题，增加的炎症，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，但这并不是 在精神障碍中进行测试此外，加速老化何时开始以及加速的速度如何仍然不确定。 进展，因为先前的研究通常从老年患者开始。预防精神病患者过早衰老 疾病将延长数百万人的寿命并改善其健康状况，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。的 萨福克县心理健康项目（SCMHP; MH 094398）提供了一个独特的机会，以填补这些关键的 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， 首次入院后超过27年的精神障碍（平均年龄30至57岁）。此外，该研究还 收集了大量关于发病前风险因素的信息。它还包括一个地理和 人口统计学匹配的无精神病对照组。对案件进行了全面评估6 在最初的二十年里。在20年（平均年龄49岁）时，两例病例（N=385）和无精神病（N=261） 各组完成全面的精神病评估、病史、体能测试， 人体测量检查、认知测试、事件相关电位电池、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， 在一个关键时期（49至57岁，预计会出现医学疾病），衰老轨迹的轨迹出现了轨迹分歧 认知和身体功能开始下降），并确定风险因素和生物学 这些弱点有助于确定衰老的路径。这一创新设计将使我们能够澄清 什么时候以及为什么衰老在精神障碍中加速，以及在哪里可以最有效地进行干预 有效地延长这一人口的预期寿命和健康。

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.