Is mental disorder a preventable cause of age-related disease? The Dunedin Study.

描述（由申请人提供）：我们建议验证一个新的假设，即持续的精神疾病史可能会加速个体向年龄相关疾病发展的风险。具体来说，该假设是，在成年早期患有慢性或复发性精神疾病的人，在38岁之前，就会表现出认知能力下降和亚临床生物标志物的异常状态，这些生物标志物已知是晚年疾病、虚弱和残疾的预后早期预警信号。我们不是把精神疾病作为一种结果来关注，而是把精神疾病作为一种可能加速衰老的可预防的“暴露”来研究。方法：我们将在达尼丁研究的背景下检验这一假设，达尼丁研究是一项从出生到38岁的纵向研究，其中有代表性的男性和女性出生队列（N=1037）。一个独特的设计特点是，在大多数精神疾病发作之前，从出生到13岁进行基线身体健康和基线神经心理学评估。据我们所知，没有其他关于精神障碍健康后果的研究具有这些前瞻性基线数据，这些数据对于测试持续性精神障碍患者的健康和神经心理功能是否恶化至关重要。在这项纵向研究中，队列成员的复发性抑郁、复发性焦虑、慢性精神分裂症综合征、持续酒精依赖和持续大麻依赖的精神病史将使用20年间反复评估的数据来定义。在这里，我们建议在38岁时再次评估队列，以收集新的数据。我们将评估亚临床健康状态的敏感结果指标，这些指标已知是晚年年龄相关疾病的预测指标：记忆和执行功能的神经心理学测试、代谢综合征、免疫生物标志物和缩短的端粒长度。之所以选择这些标记，是因为它们在30多岁的人群中显示出有意义的差异，并且是已知的痴呆症、心血管疾病和糖尿病的早期预警信号。创新与意义：人们的预期寿命越来越长。政策制定者和公民关心的是，我们的额外寿命应该是健康的、富有成效的和愉快的，而不是疾病和残疾的额外寿命。为了预防与年龄有关的疾病和提高健康预期，需要进行研究，以确定在成年早期至中期可以成功治疗的候选风险目标。如果我们提出的研究证明精神障碍加速年龄相关疾病的亚临床进展的假设是正确的，这将意味着年龄相关疾病可以通过在生命早期成功治疗精神障碍来减少。公共卫生相关性：随着预期寿命越来越长，政策制定者和公民关心的是，我们额外的岁月应该是健康的、富有成效的和愉快的，而不是疾病和残疾的额外岁月。为了预防与年龄有关的疾病，需要进行研究，以确定在成年早期到中期，在与年龄有关的疾病发病之前可以成功治疗的候选风险目标。如果我们提出的研究证明精神障碍加速年龄相关疾病的亚临床进展的假设是正确的，这将意味着通过在生命早期成功治疗精神障碍，可以减少年龄相关疾病。

DESCRIPTION (provided by applicant): We propose to test the novel hypothesis that a persistent history of psychiatric disorder might accelerate individuals' risk of progression toward age-related disease. Specifically, the hypothesis is that people who suffer chronic or recurrent psychiatric disorders during early adulthood will, already by age 38, show cognitive decline and abnormal status on sub-clinical biomarkers that are known to be prognostic early warning signs for late-life diseases, frailty and disability. Rather than focus on psychiatric disorders as an outcome, we study psychiatric disorders as a potentially preventable `exposure' that may accelerate aging. METHOD: We will test this hypothesis in the context of the Dunedin Study, a longitudinal study from birth to age 38 of a representative birth cohort of men and women (N=1037). A unique design feature is that baseline physical health and baseline neuropsychological assessments were carried out from birth to age 13, prior to the onset of most psychiatric disorders. To our knowledge, no other study of the health consequences of psychiatric disorder has these prospective baseline data, which are essential to test whether health and neuropsychological functions have deteriorated in individuals with persistent psychiatric disorder. Cohort members' psychiatric histories of recurrent Depression, recurrent Anxiety, chronic Schizophrenia-syndrome, persistent Alcohol Dependence, and persistent Cannabis Dependence will be defined using data from repeated assessments across 20 intervening years in this longitudinal study. Here we propose to assess the cohort again at age 38, for new data collection. We will assess sensitive outcome measures of sub-clinical health status that are known predictors of age-related diseases in later life: neuropsychological tests of memory and executive functions, the metabolic syndrome, immunological biomarkers, and shortened telomere length. These markers were chosen because they show meaningful variation among people in their late 30's and are known early warning signs for dementia, cardiovascular disease and diabetes. INNOVATION AND SIGNIFICANCE: Life expectancy is growing longer and longer. Policy makers and citizens are concerned that our extra years of life should be healthy, productive, and enjoyable, not extra years of disease and disability. The hope of preventing age-related diseases and of increasing health expectancy requires research to identify candidate risk targets that can be treated successfully, in early- to-middle adulthood. If the hypothesis that psychiatric disorder accelerates the sub-clinical progression toward age-related disease were shown to be true by our proposed research, this would imply that age- related disease could be reduced by successfully treating psychiatric disorders early in life. PUBLIC HEALTH RELEVANCE: As life expectancy grows longer and longer, policy makers and citizens are concerned that our extra years should be healthy, productive, and enjoyable, not extra years of disease and disability. The hope of preventing age-related diseases requires research to identify candidate risk targets that can be treated successfully, in early-to-middle adulthood, before the onset of age-related disease. If the hypothesis that psychiatric disorder accelerates the sub-clinical progression toward age-related disease were shown to be true by our proposed research, this would imply that age-related diseases could be reduced by successfully treating psychiatric disorders early in life.