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

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.

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. METHOD: We will test this hypothesis in the Dunedin Study, a longitudinal study from birth to age 38 of a representative birth cohort of New Zealand 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 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. 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 show meaningful variation among people in their late 30's and are known early warning signs for dementia, cardiovascular disease and diabetes.

Please see our "Pathways to Impact" statement for specific plans. Briefly...

The intended non-academic beneficiaries of this research are individuals who experience mental disorder, health-care providers, government, and taxpayers at large. 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 life. If the hypothesis that psychiatric disorder accelerates the sub-clinical progression toward age-related disease is 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. Thus, our proposed research could potentially increase the political will to deliver preventions and treatments to individuals who suffer mental disorder in early life. Such interventions in turn could reduce the burden of mental illness and age-related disease on the health-care delivery service. Reducing the burden of mental illness and age-related diseases could in turn reduce costs to government and taxpayers, and increase national productivity and wellbeing for the UK.

Here we refer to the MRC E-val website's page entitled Dissemination of Research to Non-Academic Audiences for MRC Programme Grant G0601483, wherein we report the ways in which our research findings have been communicated to non-academic users in the past 5 years. Full descriptions are provided for the following activities on the E-val site. We expect to engage in very similar dissemination activities in the next 5 years.

The Science of Us, a documentary Film series by TV-NZ
A Lethal Inheritance: A Mother Uncovers the Science Behind Three Generations of Mental Illness, atrade book published by Prometheus Press
Public Broadcasting System, Sesame Street, a TV programme to teach our findings about self control to children
Media coverage of research on self control
Media coverage of our work on stress & inflammation
Media coverage of our work on gene-environment interaction
Nature's Great Experiment, a Wellcome Trust Art Exhibit
Dissemination of our findings on work stress
Media coverage of our findings on cannabis and gum disease
Media coverage of our findings on early substance abuse
Media coverage of our findings on sleep
Media coverage of our findings on neighbourhood effects on children
Media coverage of our findings on family history
More media coverage of findings on stress and inflammation
Media coverage of our findings on the prevalence of mental disorders
Dissemination of findings on schizophrenia
2 videos about our research programme, in the internet.
Royal society public soiree: Behaving Badly
High visibility public lectures by TE Moffitt and A Caspi, and our trainees
Training videos
Continuing education teaching for medical professionals

As a result of these public dissemination activities, and others like them, our research under this programme grant influences policy, as reported in detail on the MRC E-Val website, which describes the recent example below.
US Supreme Court Amicus Briefs
British Academy Policy Report
US National Academy of Sciences Panel on Demand for Drugs
Wrote DSM-V diagnosis for conduct disorder, ADHD and ODD
US National Cancer Institute Report
US Institute of Medicine Report
US National Academy of Sciences 21st Century Skills
Canadian Academy of Health Sciences Expert Panel
National Academy of Sciences, Advisory Committee on Law and Justice
Usefulness of research to govt bodies internationally
Chair policy seminars at the Nuffield Foundation
Early Intervention Next Steps: A report to Her Majesty's Govt. by G Allen MP