avshalom caspi

People who experience trauma and develop posttraumatic stress disorder (PTSD) are at increased risk for poor health. One mechanism that could explain this risk is accelerated biological aging, which is associated with the accumulation of chronic diseases, disability, and premature mortality. Using data from 2309 post-9/11 United States military veterans who participated in the VISN 6 MIRECC’s Post-Deployment Mental Health Study, we tested whether PTSD and trauma exposure were associated with accelerated rate of biological aging, assessed using a validated DNA methylation (DNAm) measure of epigenetic aging—DunedinPACE. Veterans with current PTSD were aging faster than those who did not have current PTSD, β = 0.18, 95% CI [0.11, 0.27], p < .001. This effect represented an additional 0.4 months of biological aging each year. Veterans were also aging faster if they reported more PTSD …

ImportancePeople who complete more education live longer lives with better health. New evidence suggests that these benefits operate through a slowed pace of biological aging. If so, measurements of the pace of biological aging could offer intermediate end points for studies of how interventions to promote education will affect healthy longevity.ObjectiveTo test the hypothesis that upward educational mobility is associated with a slower pace of biological aging and increased longevity.Design, Setting, and ParticipantsThis prospective cohort study analyzed data from 3 generations of participants in the Framingham Heart Study: (1) the original cohort, enrolled beginning in 1948; (2) the Offspring cohort, enrolled beginning in 1971; and (3) the Gen3 cohort, enrolled beginning in 2002. A 3-generation database was constructed to quantify intergenerational educational mobility. Mobility data were linked with blood …

As societies age, policy makers need tools to understand how demographic aging will affect population health and to develop programs to increase healthspan. The current metrics used for policy analysis do not distinguish differences caused by early-life factors, such as prenatal care and nutrition, from those caused by ongoing changes in peoples bodies due to aging. Here we introduce an adapted Pace of Aging method designed to quantify differences between individuals and populations in the speed of aging-related health declines. The adapted Pace of Aging method, implemented in data from N=13,626 older adults in the US Health and Retirement Study, integrates longitudinal data on blood biomarkers, physical measurements, and functional tests. It reveals stark differences in rates of aging between population subgroups and demonstrates strong and consistent prospective associations with incident morbidity, disability, and mortality. Pace of Aging can advance the population science of healthy longevity.

Perceptions of crime detection risk (eg, risk of arrest) play an integral role in the criminal decision-making process. Yet, the sources of variation in those perceptions are not well understood. Do individuals respond to changes in legal policy or is perception of detection risk shaped like other perceptions—by experience, heuristics, and with biases? We applied a developmental perspective to study self-reported perception of detection risk. We test four hypotheses against data from the Dunedin Longitudinal Study (analytic sample of N= 985 New Zealanders), a study that spans 20 years of development (Ages 18–38, years 1990–2011). We reach four conclusions:(1) people form their perception of detection risk early in the life course;(2) perception of detection risk may be general rather than unique to each crime type;(3) population-level perceptions are stable between adolescence and adulthood; but (4) people …

Background: The WNT signaling pathway is involved in a wide range of developmental events and maintenance of homeostasis in adult tissue, including lung development and health. WNT signaling genes have also been suggested to play a role in pathogenesis of lung diseases such as chronic obstructive pulmonary disease (COPD) and asthma.Aims and Objectives: The aim of this meta-analysis was to identify consistent disease markers for COPD, asthma, forced expiratory volume in one second (FEV1), and forced vital capacity (FVC) in nine genes of the WNT signaling cascade pathway (WNT10b, WIF1, WISP1, SFRP2, SFRP5, DKK1, Axin2, TCF7L2, and FZD3) using genome-wide association data from six European cohort studies.Methods: The six European cohort studies included are: B58C (UK), ECRHS (multicentre), EGEA (France), GINI / LISA (Germany), NFBC1966 (Finland), and SAPALDIA …

Objective:To determine whether differences exist in mid-adulthood cognitive functioning in people with and without history of mild traumatic brain injury (mTBI).Setting:Community-based study.Participants:People born between April 1, 1972, and March 31, 1973, recruited into the Dunedin Multidisciplinary Health and Development Longitudinal Study, who completed neuropsychological assessments in mid-adulthood. Participants who had experienced a moderate or severe TBI or mTBI in the past 12 months were excluded.Design:Longitudinal, prospective, observational study.Main Measures:Data were collected on sociodemographic characteristics, medical history, childhood cognition (between 7 and 11 years), and alcohol and substance dependence (from 21 years of age). mTBI history was determined from accident and medical records (from birth to 45 years of age). Participants were classified as having 1 mTBI …

Social isolation and loneliness have been associated with poor health and increased risk for mortality, and inflammation might explain this link. We used data from the Danish TRIAGE Study of acutely admitted medical patients (N = 6,144, mean age 60 years), and from two population-representative birth cohorts: the New Zealand Dunedin Longitudinal Study (N = 881, age 45) and the UK Environmental Risk (E-Risk) Longitudinal Twin Study (N = 1448, age 18), to investigate associations of social isolation with three markers of systemic inflammation: C-reactive protein (CRP), interleukin-6 (IL-6), and a newer inflammation marker, soluble urokinase plasminogen activator receptor (suPAR), which is thought to index systemic chronic inflammation. In the TRIAGE Study, socially isolated patients (those living alone) had significantly higher median levels of suPAR (but not CRP or IL-6) compared with patients not living by …

The aim of this study was to use longitudinal population-based data to examine the associations between childhood sexual abuse (CSA) and risk for adverse outcomes in multiple life domains across adulthood. In 937 individuals followed from birth to age 45y, we assessed associations between CSA (retrospectively reported at age 26y) and the experience of 22 adverse outcomes in seven domains (physical, mental, sexual, interpersonal, economic, antisocial, multi-domain) from young adulthood to midlife (26 to 45y). Analyses controlled for sex, socioeconomic status, prospectively reported child harm and household dysfunction adverse childhood experiences, and adult sexual assault, and considered different definitions of CSA. After adjusting for confounders, CSA survivors were more likely than their peers to experience internalizing, externalizing, and thought disorders, suicide attempts, health risk behaviors …

Biological aging is the correlated decline of multi-organ system integrity central to the etiology of many age-related diseases. A novel epigenetic measure of biological aging, DunedinPACE, is associated with cognitive dysfunction, incident dementia, and mortality. Here, we tested for associations between DunedinPACE and structural MRI phenotypes in three datasets spanning midlife to advanced age: the Dunedin Study (age=45 years), the Framingham Heart Study Offspring Cohort (mean age=63 years), and the Alzheimer’s Disease Neuroimaging Initiative (mean age=75 years). We also tested four additional epigenetic measures of aging: the Horvath clock, the Hannum clock, PhenoAge, and GrimAge. Across all datasets (total N observations=3380; total N individuals=2322), faster DunedinPACE was associated with lower total brain volume, lower hippocampal volume, greater burden of white matter …

Over the past 10 years, the general factor of psychopathology, p, has attracted interest and scrutiny. We review the history of the idea that all mental disorders share something in common, p; how we arrived at this idea; and how it became conflated with a statistical representation, the bifactor model. We then leverage data from the Environmental Risk Longitudinal Twin Study to examine the properties and nomological network of different statistical representations of p. We found that p performed similarly regardless of how it was modeled, suggesting that if the sample and content are the same, the resulting p factor will be similar. We suggest that the meaning of p is not to be found by dueling over statistical models but by conducting well-specified criterion-validation studies and developing new measurement approaches. We outline new directions to refresh research efforts to uncover what all mental disorders have in …

Adversity that exhibits continuity across the life course has long-term detrimental effects on physical and mental health. Using 920 participants from the Dunedin Study, we tested the following hypotheses: (a) Children (ages 3–15) who experienced adversity would also tend to experience adversity in adulthood (ages 32–45), and (2) interim personality traits in young adulthood (ages 18–26) would help account for this longitudinal association. Children who experienced more adversity tended to also experience more stressful life events as adults, β = 0.11, 95% confidence interval [CI] = [0.04, 0.18], p = .002. Negative emotionality—particularly its subfacet alienation, characterized by mistrust of others—helped explain this childhood-to-midlife association (indirect effect: β = 0.06, 95% CI = [0.04, 0.09], p < .001). Results were robust to adjustment for sex, socioeconomic origins, childhood IQ, preschool temperament, and …

INTRODUCTION Dementia risk may be elevated in socioeconomically disadvantaged neighborhoods. Reasons for this remain unclear, and this elevation has yet to be shown at a national population level. METHODS We tested whether dementia was more prevalent in disadvantaged neighborhoods across the New Zealand population (N = 1.41 million analytic sample) over a 20‐year observation. We then tested whether premorbid dementia risk factors and MRI‐measured brain‐structure antecedents were more prevalent among midlife residents of disadvantaged neighborhoods in a population‐representative NZ‐birth‐cohort (N = 938 analytic sample). RESULTS People residing in disadvantaged neighborhoods were at greater risk of dementia (HR per‐quintile‐disadvantage‐increase = 1.09, 95% confidence interval [CI]:1.08‐1.10) and, decades before clinical endpoints typically emerge, evidenced elevated …

Objectives Childhood caries is associated with poorer self‐rated general health in adulthood, but it remains unclear whether that holds for physical health and aging. The aim of this study was to identify whether age‐5 caries is associated with (a) biomarkers for poor physical health, and (b) the pace of aging (PoA) by age 45 years. Methods Participants are members of the Dunedin Multidisciplinary Health and Development Study birth cohort. At age 45, 94.1% (n = 938) of those still alive took part. Data on age‐5 caries experience and age‐45 health biomarkers were collected. The PoA captures age‐related decline across the cardiovascular, metabolic, renal, immune, dental and pulmonary systems from age 26 to 45 years. We used (a) generalized estimating equations to examine associations between age‐5 caries and poor physical health by age 45 years, and (b) ordinary least squares regression to …

BackgroundMidlife adults are experiencing a crisis of deaths of despair (i.e. deaths from suicide, drug overdose, and alcohol-related liver disease). We tested the hypothesis that a syndrome of despair-related maladies at midlife is preceded by psychopathology during adolescence.MethodsParticipants are members of a representative cohort of 1037 individuals born in Dunedin, New Zealand in 1972–73 and followed to age 45 years, with 94% retention. Adolescent mental disorders were assessed in three diagnostic assessments at ages 11, 13, and 15 years. Indicators of despair-related maladies across four domains – suicidality, substance misuse, sleep problems, and pain – were assessed at age 45 using multi-modal measures including self-report, informant-report, and national register data.ResultsWe identified and validated a syndrome of despair-related maladies at midlife involving suicidality, substance …

Mapping individual differences in brain function has been hampered by poor reliability as well as limited interpretability. Leveraging patterns of brain‐wide functional connectivity (FC) offers some promise in this endeavor. In particular, a macroscale principal FC gradient that recapitulates a hierarchical organization spanning molecular, cellular, and circuit level features along a sensory‐to‐association cortical axis has emerged as both a parsimonious and interpretable measure of individual differences in behavior. However, the measurement reliabilities of this FC gradient have not been fully evaluated. Here, we assess the reliabilities of both global and regional principal FC gradient measures using test–retest data from the young adult Human Connectome Project (HCP‐YA) and the Dunedin Study. Analyses revealed that the reliabilities of principal FC gradient measures were (1) consistently higher than those for …

Clinical relevanceMacular drusen are associated with age-related maculopathy but are not an ocular manifestation or biomarker of systemic ageing.BackgroundMacular drusen are the first sign of age-related maculopathy, an eye disease for which age is the strongest risk factor. The aim of this cohort study was to investigate whether macular drusen in midlife – a sign of the earliest stages of age-related macular degeneration (AMD) – are associated with accelerated biological ageing more generally.MethodsMembers of the long-running Dunedin Multidisciplinary Health and Development Study (hereafter the Dunedin Study, n = 1037) underwent retinal photography at their most recent assessment at the age of 45 years. Images were graded for the presence of AMD using a simplified scale from the Age-Related Eye Disease Study (AREDS). Accelerated ageing was assessed by (i) a measure of Pace of Ageing …

Objective People who eat healthier diets are less likely to develop dementia, but the biological mechanism of this protection is not well understood. We tested the hypothesis that healthy diet protects against dementia because it slows the pace of biological aging. Methods We analyzed Framingham Offspring Cohort data. We included participants ≥60 years‐old, free of dementia and having dietary, epigenetic, and follow‐up data. We assessed healthy diet as long‐term adherence to the Mediterranean‐Dash Intervention for Neurodegenerative Delay diet (MIND, over 4 visits spanning 1991–2008). We measured the pace of aging from blood DNA methylation data collected in 2005–2008 using the DunedinPACE epigenetic clock. Incident dementia and mortality were defined using study records compiled from 2005 to 2008 visit through 2018. Results Of n = 1,644 included participants (mean age 69.6, 54 …

Adverse childhood experiences (ACEs) are associated with poorer health, which has spurred public health efforts to reduce the number of adverse events children experience. Unfortunately, it is unlikely that all ACEs can be prevented. For adults who already experienced ACEs in childhood, what psychological, social, and behavioral intervention targets might reduce risk for negative health outcomes? To provide insight into the “black box” of psychosocial mechanisms linking ACEs to poor health, our study used data from the Dunedin Study, a longitudinal cohort assessed from birth to age 45. Mediation models (N = 859) were used to examine whether candidate psychosocial variables in adulthood explained the association between childhood ACEs and health in midlife. Potential psychosocial mediators included stressful life events, perceived stress, negative emotionality, and health behaviors. Children who …

BackgroundSchizophrenia is associated with increased risk of developing multiple aging-related diseases, including metabolic, respiratory, and cardiovascular diseases, and Alzheimer’s and related dementias, leading to the hypothesis that schizophrenia is accompanied by accelerated biological aging. This has been difficult to test because there is no widely accepted measure of biological aging. Epigenetic clocks are promising algorithms that are used to calculate biological age on the basis of information from combined cytosine-phosphate-guanine sites (CpGs) across the genome, but they have yielded inconsistent and often negative results about the association between schizophrenia and accelerated aging. Here, we tested the schizophrenia-aging hypothesis using a DNA methylation measure that is uniquely designed to predict an individual’s rate of aging.MethodsWe brought together 5 case-control …

Stress and stressful events are associated with poorer health. There are multiple approaches to measure stress—from assessing subjective perceptions of stress to assessing the development of posttraumatic stress disorder (PTSD)—and multiple periods that can be assessed across the lifespan. How might stress result in poorer health? One plausible physiological mechanism is accelerated biological aging, which precedes many poor health outcomes. Our study tested which measures of stress were associated with accelerated biological aging in adulthood using 955 participants from the Dunedin Longitudinal Study. The measures of stress included perceived stress, stressful life events, adverse childhood experiences (ACEs), and PTSD assessed between ages 32 to 45 years and accelerated biological aging in midlife was measured using the Pace of Aging. Higher levels of all four stress measures were …