Psychiatric disorder and accelerated aging: The Dunedin Multidisciplinary Health and Development Longitudinal Cohort Study

背景：我们提出检验一种新的假设，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30多岁之前，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、虚弱和残疾的预后预警信号。与其将精神疾病作为结果来关注，我们建议将精神疾病作为可能加速衰老的潜在可预防的“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，研究对象为新西兰男性和女性的代表性出生队列（N=1037），队列保留率超过90%。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障碍的个体的健康和神经心理功能是否真的恶化至关重要。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在这项纵向研究中使用25年重复评估的数据来定义。在MRC的资助下，我们最近再次对38岁的队列进行了评估。我们评估了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测试、代谢综合征、炎症生物标志物、视网膜微血管和缩短的端粒长度。之所以选择这些标志物，是因为它们是已知的痴呆症、心血管疾病和糖尿病的早期预警信号。这些指标在接近40岁的人群中显示出有意义的差异，达尼丁的研究有足够数量的病例来测试复发性精神疾病是否能预测健康结果，同时控制儿童时期的基线健康状况。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。

BACKGROUND: 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 their late thirties, 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 the outcome, here we propose to 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 New Zealand men and women (N=1037) with over 90% cohort retention. 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 actually deteriorated in individuals who have experienced 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 25 intervening years in this longitudinal study. With MRC funding, we most recently assessed the cohort again at age 38. We assessed 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, inflammation biomarkers, retinal micro-vasculature, and shortened telomere length. These markers were chosen because they are known early warning signs for dementia, cardiovascular disease and diabetes. The markers show meaningful variation among people in their late 30's, and the Dunedin study has sufficient numbers of cases to test whether recurrent psychiatric disorder predicts health outcomes, while controlling for baseline health status in childhood. 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.