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

描述（由申请人提供）：我们建议测试一个新的假设，即持续的精神疾病史可能会加速个体发展为与年龄相关的疾病的风险。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到 38 岁时，就会表现出认知能力下降和亚临床生物标志物异常状态，这些生物标志物被认为是晚年疾病、虚弱和残疾的预后早期预警信号。我们不是将精神疾病作为结果来研究，而是将精神疾病视为一种可能加速衰老的潜在可预防的“暴露”。方法：我们将在达尼丁研究的背景下检验这一假设，该研究是一项对具有代表性的男性和女性出生队列 (N=1037) 从出生到 38 岁的纵向研究。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是在从出生到 13 岁（大多数精神疾病发作之前）进行的。据我们所知，没有其他关于精神疾病对健康影响的研究拥有这些前瞻性基线数据，这些数据对于测试患有持续性精神疾病的个体的健康和神经心理功能是否恶化至关重要。队列成员的复发性抑郁症、复发性焦虑症、慢性精神分裂症综合征、持续性酒精依赖和持续性大麻依赖的精神病史将使用这项纵向研究中 20 年的重复评估数据来定义。在这里，我们建议在 38 岁时再次评估该队列，以收集新的数据。我们将评估亚临床健康状况的敏感结果指标，这些指标是晚年与年龄相关疾病的已知预测因子：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。选择这些标志物是因为它们在 30 多岁的人群中表现出有意义的差异，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，我们的余生应该是健康的、富有成效的和愉快的，而不是余生是疾病和残疾。为了预防与年龄相关的疾病和提高健康预期，需要进行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疾病加速与年龄相关疾病的亚临床进展的假设是正确的，那么这将意味着通过在生命早期成功治疗精神疾病可以减少与年龄相关的疾病。公共卫生相关性：随着预期寿命越来越长，政策制定者和公民担心我们的额外岁月应该是健康的、富有成效的和愉快的，而不是疾病和残疾的额外岁月。预防与年龄相关的疾病的希望需要研究来确定可以在成年早期到中期、与年龄相关的疾病发作之前成功治疗的候选风险目标。如果我们提出的研究证明精神疾病加速与年龄相关疾病的亚临床进展的假设是正确的，那么这将意味着通过在生命早期成功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.