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

描述(由申请人提供)：我们建议测试这一新的假设，即持续的精神障碍病史可能会加速个人发展为年龄相关疾病的风险。具体地说，假设是，在成年早期患有慢性或反复精神障碍的人，在38岁之前，就会在亚临床生物标志物上表现出认知能力下降和异常状态，这些生物标志物被认为是老年疾病、虚弱和残疾的预后预警信号。我们没有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可以预防的、可能会加速衰老的“暴露”来研究。方法：我们将在达尼丁研究的背景下验证这一假设，达尼丁研究是一项从出生到38岁的纵向研究，研究对象是具有代表性的男女出生队列(N=1037)。一个独特的设计特点是，基线身体健康和基线神经心理评估从出生到13岁，在大多数精神疾病发生之前进行。据我们所知，没有其他关于精神障碍对健康影响的研究拥有这些预期的基线数据，这些数据对于测试患有持续性精神障碍的个人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，队列成员的反复抑郁、反复焦虑、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年间重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，以进行新的数据收集。我们将评估亚临床健康状况的敏感结果指标，这些指标是已知的年龄相关疾病的预测指标：记忆和执行功能的神经心理测试、代谢综合征、免疫生物标记物和端粒缩短。之所以选择这些标记物，是因为它们在近30岁的S人群中显示出显著的差异，是痴呆症、心血管疾病和糖尿病的已知早期预警信号。创新和意义：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、多产和愉快的，而不是额外的疾病和残疾。预防与年龄相关的疾病和提高健康预期的希望需要研究，以确定可以在成年早期到中期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会加速亚临床进展为年龄相关疾病的假设是正确的，这将意味着通过成功地在生命早期治疗精神疾病可以减少与年龄相关的疾病。与公共健康相关：随着预期寿命越来越长，政策制定者和公民关心的是，我们多活的几年应该是健康、多产和愉快的，而不是多几年的疾病和残疾。预防年龄相关疾病的希望需要研究确定候选风险目标，这些目标可以在与年龄相关的疾病发生之前，在成年早期到中期成功治疗。如果我们建议的研究证明精神障碍加速亚临床进展为年龄相关疾病的假设是正确的，这将意味着通过成功地在生命早期治疗精神疾病可以减少与年龄相关的疾病。

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.