Search

Abstract Background There is a rapid decline in moderate-to-vigorous physical activity (MVPA) during middle childhood and adolescence. Information on the environmental factors implicated in this decline is limited. This study focuses on family factors associated with the rate of decline in objectively measured physical activity during middle childhood and adolescence. Methods Longitudinal analysis of 801 participants from 10 US sites in the NICHD Study of Early Child Care and Youth Development whose data included accelerometer-determined levels of moderate-to-vigorous physical activity (MVPA) between ages 9 and 15 years, as well as family process, BMI and demographic information. The sample included an even split of boys (49%) and girls (51%), was predominantly white (77%), and contained about 26% low income and 19% single parent families. The outcome measure was mean MVPA. It was based on 4 to 7 days of monitored physical activity. Results Boys with lower parental monitoring scores and more days of parental encouragement had significantly more minutes of MVPA at age 9 years. The effect of parental monitoring, however, was moderated by early puberty. High parental monitoring was associated with decreased activity levels for boys experiencing later puberty and increased activity for boy experiencing early puberty. Minutes of MVPA for boys living in the Midwest decreased at significantly faster rates than boys living in any other region; and boys in the South declined faster than boys in the West. Girls in the Midwest and South declined faster than girls in the West and Northeast. Among girls, more days of parental exercise and transportation to activities were associated with more MVPA per day at age 9. However, more parental transportation to activities and less monitoring was associated with faster linear declines in daughters' MVPA between the ages of 9 and 15 years. For girls who experienced puberty early, parental encouragement was associated with more MVPA. Conclusions Parenting processes, such as monitoring and encouragement, as well as the parents' own level of physical activity, showed significant, but small, gender-specific associations with MVPA levels at age nine and the linear rate of decline in MVPA between ages 9 and 15.

Drawing on psychological and sociological theories of crime causation, we tested the hypothesis that genetic risk for low educational attainment (assessed via a genome-wide polygenic score) is associated with criminal offending. We further tested hypotheses of how polygenic risk relates to the development of antisocial behavior from childhood through adulthood. Across the Dunedin and Environmental Risk (E-Risk) birth cohorts of individuals growing up 20 years and 20,000 kilometers apart, education polygenic scores predicted risk of a criminal record with modest effects. Polygenic risk manifested during primary schooling in lower cognitive abilities, lower self-control, academic difficulties, and truancy, and it was associated with a life-course-persistent pattern of antisocial behavior that onsets in childhood and persists into adulthood. Crime is central in the nature-nurture debate, and findings reported here demonstrate how molecular-genetic discoveries can be incorporated into established theories of antisocial behavior. They also suggest that improving school experiences might prevent genetic influences on crime from unfolding.

Abstract Background There is a rapid decline in moderate-to-vigorous physical activity (MVPA) during middle childhood and adolescence. Information on the environmental factors implicated in this decline is limited. This study focuses on family factors associated with the rate of decline in objectively measured physical activity during middle childhood and adolescence. Methods Longitudinal analysis of 801 participants from 10 US sites in the NICHD Study of Early Child Care and Youth Development whose data included accelerometer-determined levels of moderate-to-vigorous physical activity (MVPA) between ages 9 and 15 years, as well as family process, BMI and demographic information. The sample included an even split of boys (49%) and girls (51%), was predominantly white (77%), and contained about 26% low income and 19% single parent families. The outcome measure was mean MVPA. It was based on 4 to 7 days of monitored physical activity. Results Boys with lower parental monitoring scores and more days of parental encouragement had significantly more minutes of MVPA at age 9 years. The effect of parental monitoring, however, was moderated by early puberty. High parental monitoring was associated with decreased activity levels for boys experiencing later puberty and increased activity for boy experiencing early puberty. Minutes of MVPA for boys living in the Midwest decreased at significantly faster rates than boys living in any other region; and boys in the South declined faster than boys in the West. Girls in the Midwest and South declined faster than girls in the West and Northeast. Among girls, more days of parental exercise and transportation to activities were associated with more MVPA per day at age 9. However, more parental transportation to activities and less monitoring was associated with faster linear declines in daughters' MVPA between the ages of 9 and 15 years. For girls who experienced puberty early, parental encouragement was associated with more MVPA. Conclusions Parenting processes, such as monitoring and encouragement, as well as the parents' own level of physical activity, showed significant, but small, gender-specific associations with MVPA levels at age nine and the linear rate of decline in MVPA between ages 9 and 15.

BACKGROUND: This study describes longitudinal changes in the composition and accuracy of modal life-sustaining treatment preferences as predictors of patients' treatment preferences. METHOD: Healthy outpatients age 65 and older and their surrogate decision makers recorded preferences for 4 treatments in 9 hypothetical illness scenarios 3 times over a period of 2 years. A statistical prediction model, based on patients' modal preferences, was created using initial responses and updated 2 years later. RESULTS: When reestimating the model at 2 years, 4 of 27 items in the model created using baseline responses no longer reached the threshold for inclusion, but 5 new items did meet criteria. All modal preference changes reflected a trend toward refusing treatment. Both the original and updated models were more accurate in predicting patients' preferences than were surrogates making concurrent predictions. Adding covariates (e.g., gender, age, presence of plans for future medical care) did not alter the model's predictive superiority over surrogates. CONCLUSIONS: Models using modal preferences are useful to patients, surrogates, and physicians when trying to accurately discern end-of-life treatment choices, but the models must be updated periodically. [ABSTRACT FROM AUTHOR]

Background: Mental disorders and physical-health conditions frequently co-occur, impacting treatment outcomes. While most prior research has focused on single pairs of mental disorders and physical-health conditions, this study explores broader associations between multiple mental disorders and physical-health conditions., Methods: Using the Norwegian primary-care register, this population-based cohort study encompassed all 2 203 553 patients born in Norway from January 1945 through December 1984, who were full-time residents from January 2006 until December 2019 (14 years; 363 million person-months). Associations between seven mental disorders (sleep disturbance, anxiety, depression, acute stress reaction, substance-use disorders, phobia/compulsive disorder, psychosis) and 16 physical-health conditions were examined, diagnosed according to the International Classification of Primary Care., Results: Of 112 mental-disorder/physical-health condition pairs, 96% of associations yielded positive and significant ORs, averaging 1.41 and ranging from 1.05 (99.99% CI 1.00-1.09) to 2.38 (99.99% CI 2.30-2.46). Across 14 years, every mental disorder was associated with multiple different physical-health conditions. Across 363 million person-months, having any mental disorder was associated with increased subsequent risk of all physical-health conditions (HRs:1.40 [99.99% CI 1.35-1.45] to 2.85 [99.99% CI 2.81-2.89]) and vice versa (HRs:1.56 [99.99% CI 1.54-1.59] to 3.56 [99.99% CI 3.54-3.58]). Associations were observed in both sexes, across age groups, and among patients with and without university education., Conclusions: The breadth of associations between virtually every mental disorder and physical-health condition among patients treated in primary care underscores a need for integrated mental and physical healthcare policy and practice. This remarkable breadth also calls for research into etiological factors and underlying mechanisms that can explain it.

How many primary-care encounters are devoted to mental-health conditions compared with physical-health conditions? Here we analyzed Norway's nationwide administrative primary-care records, extracting all doctor-patient encounters occurring during 14 years (2006-2019) for the population aged 0-100 years. Encounters were recorded according to the International Classification of Primary Care. We compared the volume of mental-health encounters against volumes for conditions in multiple different body systems. A total of 4,875,722 patients generated 354,516,291 encounters. One in 9 encounters (11.7%) involved a mental-health condition. Only musculoskeletal conditions accounted for a greater share of primary-care physicians' attention. The volume of mental-health encounters in primary care equaled encounters for infections, cardiovascular and respiratory conditions and exceeded encounters for pain, injuries, metabolic, digestive, skin, urological, reproductive and sensory conditions. Primary-care physicians frequently treat complex mental-health conditions in patients of every age. These physicians may have a more important role in preventing the escalation of mental-health problems than heretofore appreciated., Competing Interests: Competing interestsAll authors declare no competing interests., (© The Author(s) 2024.)

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 Bi-Factor Model. We then leverage the Environmental Risk (E-Risk) longitudinal twin study to examine the properties and nomological network of different statistical representations of p. We find that p performed similarly regardless of how it was modelled, 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 common.

Background: Midlife 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., Methods: Participants 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., Results: We identified and validated a syndrome of despair-related maladies at midlife involving suicidality, substance misuse, sleep problems, and pain. Adults who exhibited a more severe syndrome of despair-related maladies at midlife tended to have had early-onset emotional and behavioral disorders [ β = 0.23, 95% CI (0.16-0.30), p < 0.001], even after adjusting for sex, childhood SES, and childhood IQ. A more pronounced midlife despair syndrome was observed among adults who, as adolescents, were diagnosed with a greater number of mental disorders [ β = 0.26, 95% CI (0.19-0.33), p < 0.001]. Tests of diagnostic specificity revealed that associations generalized across different adolescent mental disorders., Conclusions: Midlife adults who exhibited a more severe syndrome of despair-related maladies tended to have had psychopathology as adolescents. Prevention and treatment of adolescent psychopathology may mitigate despair-related maladies at midlife and ultimately reduce deaths of despair.

Genetic inheritance is not the only way parents' genes may affect children. It is also possible that parents' genes are associated with investments into children's development. We examined evidence for links between parental genetics and parental investments, from the prenatal period through to adulthood, using data from six population-based cohorts in the UK, US and New Zealand, together totalling 36,566 parents. Our findings revealed associations between parental genetics-summarized in a genome-wide polygenic score-and parental behaviour across development, from smoking in pregnancy, breastfeeding in infancy, parenting in childhood and adolescence, to leaving a wealth inheritance to adult children. Effect sizes tended to be small at any given time point, ranging from RR = 1.12 (95% confidence interval (95%CI) 1.09, 1.15) to RR = 0.76 (95%CI 0.72, 0.80) during the prenatal period and infancy; β = 0.07 (95%CI 0.04, 0.11) to β = 0.29 (95%CI 0.27, 0.32) in childhood and adolescence, and RR = 1.04 (95%CI 1.01, 1.06) to RR = 1.11 (95%CI 1.07, 1.15) in adulthood. There was evidence for accumulating effects across development, ranging from β = 0.15 (95%CI 0.11, 0.18) to β = 0.23 (95%CI 0.16, 0.29) depending on cohort. Our findings are consistent with the interpretation that parents pass on advantages to offspring not only via direct genetic transmission or purely environmental paths, but also via genetic associations with parental investment from conception to wealth inheritance., (© 2023. The Author(s).)

Knowledge of a person's risk for Alzheimer's disease and related dementias (ADRDs) is required to triage candidates for preventive interventions, surveillance, and treatment trials. ADRD risk indexes exist for this purpose, but each includes only a subset of known risk factors. Information missing from published indexes could improve risk prediction. In the Dunedin Study of a population-representative New Zealand-based birth cohort followed to midlife ( N  = 938, 49.5% female), we compared associations of four leading risk indexes with midlife antecedents of ADRD against a novel benchmark index comprised of nearly all known ADRD risk factors, the Dunedin ADRD Risk Benchmark (DunedinARB). Existing indexes included the Cardiovascular Risk Factors, Aging, and Dementia index (CAIDE), LIfestyle for BRAin health index (LIBRA), Australian National University Alzheimer's Disease Risk Index (ANU-ADRI), and risks selected by the Lancet Commission on Dementia. The Dunedin benchmark was comprised of 48 separate indicators of risk organized into 10 conceptually distinct risk domains. Midlife antecedents of ADRD treated as outcome measures included age-45 measures of brain structural integrity [magnetic resonance imaging-assessed: (i) machine-learning-algorithm-estimated brain age, (ii) log-transformed volume of white matter hyperintensities, and (iii) mean grey matter volume of the hippocampus] and measures of brain functional integrity [(i) objective cognitive function assessed via the Wechsler Adult Intelligence Scale-IV, (ii) subjective problems in everyday cognitive function, and (iii) objective cognitive decline measured as residualized change in cognitive scores from childhood to midlife on matched Weschler Intelligence scales]. All indexes were quantitatively distributed and proved informative about midlife antecedents of ADRD, including algorithm-estimated brain age ( β 's from 0.16 to 0.22), white matter hyperintensities volume ( β 's from 0.16 to 0.19), hippocampal volume ( β 's from -0.08 to -0.11), tested cognitive deficits ( β 's from -0.36 to -0.49), everyday cognitive problems ( β 's from 0.14 to 0.38), and longitudinal cognitive decline ( β 's from -0.18 to -0.26). Existing indexes compared favourably to the comprehensive benchmark in their association with the brain structural integrity measures but were outperformed in their association with the functional integrity measures, particularly subjective cognitive problems and tested cognitive decline. Results indicated that existing indexes could be improved with targeted additions, particularly of measures assessing socioeconomic status, physical and sensory function, epigenetic aging, and subjective overall health. Existing premorbid ADRD risk indexes perform well in identifying linear gradients of risk among members of the general population at midlife, even when they include only a small subset of potential risk factors. They could be improved, however, with targeted additions to more holistically capture the different facets of risk for this multiply determined, age-related disease., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background and Objectives: DNA methylation algorithms are increasingly used to estimate biological aging; however, how these proposed measures of whole-organism biological aging relate to aging in the brain is not known. We used data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the Framingham Heart Study (FHS) Offspring Cohort to test the association between blood-based DNA methylation measures of biological aging and cognitive impairment and dementia in older adults., Methods: We tested 3 "generations" of DNA methylation age algorithms (first generation: Horvath and Hannum clocks; second generation: PhenoAge and GrimAge; and third generation: DunedinPACE, Dunedin Pace of Aging Calculated from the Epigenome) against the following measures of cognitive impairment in ADNI: clinical diagnosis of dementia and mild cognitive impairment, scores on Alzheimer disease (AD) / Alzheimer disease and related dementias (ADRD) screening tests (Alzheimer's Disease Assessment Scale, Mini-Mental State Examination, and Montreal Cognitive Assessment), and scores on cognitive tests (Rey Auditory Verbal Learning Test, Logical Memory test, and Trail Making Test). In an independent replication in the FHS Offspring Cohort, we further tested the longitudinal association between the DNA methylation algorithms and the risk of developing dementia., Results: In ADNI ( N = 649 individuals), the first-generation (Horvath and Hannum DNA methylation age clocks) and the second-generation (PhenoAge and GrimAge) DNA methylation measures of aging were not consistently associated with measures of cognitive impairment in older adults. By contrast, a third-generation measure of biological aging, DunedinPACE, was associated with clinical diagnosis of Alzheimer disease (beta [95% CI] = 0.28 [0.08-0.47]), poorer scores on Alzheimer disease/ADRD screening tests (beta [Robust SE] = -0.10 [0.04] to 0.08[0.04]), and cognitive tests (beta [Robust SE] = -0.12 [0.04] to 0.10 [0.03]). The association between faster pace of aging, as measured by DunedinPACE, and risk of developing dementia was confirmed in a longitudinal analysis of the FHS Offspring Cohort ( N = 2,264 individuals, hazard ratio [95% CI] = 1.27 [1.07-1.49])., Discussion: Third-generation blood-based DNA methylation measures of aging could prove valuable for measuring differences between individuals in the rate at which they age and in their risk for cognitive decline, and for evaluating interventions to slow aging., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Importance: Biological aging is a distinct construct from health; however, people who age quickly are more likely to experience poor health. Identifying pediatric health conditions associated with accelerated aging could help develop treatment approaches to slow midlife aging and prevent poor health in later life., Objective: To examine the association between 4 treatable health conditions in adolescence and accelerated aging at midlife., Design, Setting, and Participants: This cohort study analyzed data from participants in the Dunedin Study, a longitudinal investigation of health and behavior among a birth cohort born between April 1, 1972, and March 31, 1973, in Dunedin, New Zealand, and followed up until age 45 years. Participants underwent an assessment at age 45 years and had data for at least 1 adolescent health condition (asthma, smoking, obesity, and psychological disorders) and outcome measure (pace of aging, gait speed, brain age, and facial age). Data analysis was performed from February 11 to September 27, 2021., Exposures: Asthma, cigarette smoking, obesity, and psychological disorders were assessed at age 11, 13, and 15 years., Main Outcomes and Measures: The outcome was a midlife aging factor composite score comprising 4 measures of biological aging: pace of aging, gait speed, brain age (specifically, BrainAGE score), and facial age., Results: A total of 910 participants (459 men [50.4%]) met the inclusion criteria, including an assessment at age 45 years. Participants who had smoked daily (0.61 [95% CI, 0.43-0.79] SD units), had obesity (0.82 [95% CI, 0.59-1.06] SD units), or had a psychological disorder diagnosis (0.43 [95% CI, 0.29-0.56] SD units) during adolescence were biologically older at midlife compared with participants without these conditions. Participants with asthma were not biologically older at midlife (0.02 [95% CI, -0.14 to 0.19] SD units) compared with those without asthma. These results remained unchanged after adjusting for childhood risk factors such as poor health, socioeconomic disadvantage, and adverse experiences., Conclusions and Relevance: This study found that adolescent smoking, obesity, and psychological disorder diagnoses were associated with older biological age at midlife. These health conditions could be treated during adolescence to reduce the risk of accelerated biological aging later in life.

Importance: Individuals with mental disorders are at an elevated risk of developing chronic age-related physical diseases. However, it is not clear whether psychopathology is also associated with processes of accelerated aging that precede the onset of age-related disease., Objective: To test the hypothesis that a history of psychopathology is associated with indicators of accelerated aging at midlife., Design, Setting, and Participants: This prospective cohort study was based on the Dunedin Multidisciplinary Health and Development Study, a population-representative birth cohort of 1037 individuals born between April 1, 1972, and March 31, 1973, in Dunedin, New Zealand. Members were followed up to age 45 years (until April 2019). Data were analyzed from January 6 to December 7, 2020., Exposures: Mental disorders were assessed in 6 diagnostic assessments from ages 18 to 45 years and transformed through confirmatory factor analysis into continuous measures of general psychopathology (p-factor) and dimensions of internalizing, externalizing, and thought disorders (all standardized to a mean [SD] of 100 [15])., Main Outcomes and Measures: Signs of aging (biological pace of aging; declines in sensory, motor, and cognitive functioning; and facial age) were assessed up to age 45 years using previously validated measures including biomarkers, clinical tests, and self-reports., Results: Of the original 1037 cohort participants, 997 were still alive at age 45 years, of whom 938 (94%) were assessed (474 men [50.5%]). Participants who had experienced more psychopathology exhibited a faster pace of biological aging (β, 0.27; 95% CI, 0.21-0.33; P < .01); experienced more difficulties with hearing (β, 0.18; 95% CI, 0.12-0.24; P < .01), vision (β, 0.08; 95% CI, 0.01-0.14; P < .05), balance (β, 0.20; 95% CI, 0.14-0.26; P < .01), and motor functioning (β, 0.19; 95% CI, 0.12-0.25; P < .01); experienced more cognitive difficulties (β, 0.24; 95% CI, 0.18-0.31; P < .01); and were rated as looking older (β, 0.20; 95% CI, 0.14-0.26; P < .01). Associations persisted after controlling for sex, childhood health indicators, maltreatment, and socioeconomic status and after taking into account being overweight, smoking, use of antipsychotic medication, and the presence of physical disease. Tests of diagnostic specificity revealed that associations were generalizable across externalizing, internalizing, and thought disorders., Conclusions and Relevance: In this cohort study, a history of psychopathology was associated with accelerated aging at midlife, years before the typical onset of age-related diseases. This link is not specific to any particular disorder family but generalizes across disorders. Prevention of psychopathology and monitoring of individuals with mental disorders for signs of accelerated aging may have the potential to reduce health inequalities and extend healthy lives.

Some humans age faster than others. Variation in biological aging can be measured in midlife, but the implications of this variation are poorly understood. We tested associations between midlife biological aging and indicators of future frailty-risk in the Dunedin cohort of 1037 infants born the same year and followed to age 45. Participants' Pace of Aging was quantified by tracking declining function in 19 biomarkers indexing the cardiovascular, metabolic, renal, immune, dental, and pulmonary systems across ages 26, 32, 38, and 45 years. At age 45 in 2019, participants with faster Pace of Aging had more cognitive difficulties, signs of advanced brain aging, diminished sensory-motor functions, older appearance, and more pessimistic perceptions of aging. People who are aging more rapidly than same-age peers in midlife may prematurely need supports to sustain independence that are usually reserved for older adults. Chronological age does not adequately identify need for such supports., Competing Interests: Competing Interests The authors declare no competing interests.

The ability to control one's own emotions, thoughts, and behaviors in early life predicts a range of positive outcomes in later life, including longevity. Does it also predict how well people age? We studied the association between self-control and midlife aging in a population-representative cohort of children followed from birth to age 45 y, the Dunedin Study. We measured children's self-control across their first decade of life using a multi-occasion/multi-informant strategy. We measured their pace of aging and aging preparedness in midlife using measures derived from biological and physiological assessments, structural brain-imaging scans, observer ratings, self-reports, informant reports, and administrative records. As adults, children with better self-control aged more slowly in their bodies and showed fewer signs of aging in their brains. By midlife, these children were also better equipped to manage a range of later-life health, financial, and social demands. Associations with children's self-control could be separated from their social class origins and intelligence, indicating that self-control might be an active ingredient in healthy aging. Children also shifted naturally in their level of self-control across adult life, suggesting the possibility that self-control may be a malleable target for intervention. Furthermore, individuals' self-control in adulthood was associated with their aging outcomes after accounting for their self-control in childhood, indicating that midlife might offer another window of opportunity to promote healthy aging., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

Background: A recent genome-wide association study identified molecular-genetic associations with age-at-first-birth. However, the meaning of these genetic discoveries is unclear. Drawing on evidence linking early pregnancy with disinhibitory behavior, we tested the hypothesis that genetic discoveries for age-at-first-birth predict disinhibition., Methods: We included participants with genotype data from the two-decade-long Environmental Risk (E-Risk) Study (N = 1,999) and the four-decade-long Dunedin Study (N = 918). We calculated a genome-wide polygenic score for age-at-first-birth and tested whether it was associated with a range of disinhibitory outcomes across the life course, including low childhood self-control; risk for externalizing psychopathology; officially recorded criminal offending; substance dependence; informant reports of disinhibitory problems; and number of lifetime sexual partners. We further tested whether associations were attributable to accelerated pubertal maturation., Results: In both cohorts, the age-at-first-birth polygenic score predicted low childhood self-control, externalizing psychopathology, officially recorded criminal offending, substance dependence, and number of sexual partners. Associations were modest, but robust across replication. Childhood disinhibition partly mediated associations between the polygenic score and reproductive behaviors. In contrast, associations were not attributable to accelerated pubertal timing., Conclusions: Genomic discoveries for age-at-first-birth are about more than reproductive biology: They provide insight into the disinhibitory traits and behaviors that accompany early parenthood. Age-at-first-birth is a useful proxy phenotype for researchers interested in disinhibition. Further, interventions that improve self-regulation abilities may benefit young parents and their children., (© 2020 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Importance: Childhood lead exposure has been linked to disrupted brain development, but long-term consequences for structural brain integrity are unknown., Objective: To test the hypothesis that childhood lead exposure is associated with magnetic resonance imaging (MRI) measurements of lower structural integrity of the brain in midlife., Design, Setting, and Participants: The Dunedin Study followed a population-representative 1972-1973 birth cohort in New Zealand (N = 564 analytic sample) to age 45 years (until April 2019)., Exposures: Childhood blood lead levels measured at age 11 years., Main Outcomes and Measures: Structural brain integrity at age 45 years assessed via MRI (primary outcomes): gray matter (cortical thickness, surface area, hippocampal volume), white matter (white matter hyperintensities, fractional anisotropy [theoretical range, 0 {diffusion is perfectly isotropic} to 100 {diffusion is perfectly anisotropic}]), and the Brain Age Gap Estimation (BrainAGE), a composite index of the gap between chronological age and a machine learning algorithm-estimated brain age (0 indicates a brain age equivalent to chronological age; positive and negative values represent an older and younger brain age, respectively). Cognitive function at age 45 years was assessed objectively via the Wechsler Adult Intelligence Scale IV (IQ range, 40-160, standardized to a mean of 100 [SD, 15]) and subjectively via informant and self-reports (z-score units; scale mean, 0 [SD, 1])., Results: Of 1037 original participants, 997 were alive at age 45 years, of whom 564 (57%) had received lead testing at age 11 years (302 [54%] male) (median follow-up, 34 [interquartile range, 33.7-34.7] years). Mean blood lead level at age 11 years was 10.99 (SD, 4.63) μg/dL. After adjusting for covariates, each 5-μg/dL higher childhood blood lead level was significantly associated with 1.19-cm2 smaller cortical surface area (95% CI, -2.35 to -0.02 cm2; P = .05), 0.10-cm3 smaller hippocampal volume (95% CI, -0.17 to -0.03 cm3; P = .006), lower global fractional anisotropy (b = -0.12; 95% CI, -0.24 to -0.01; P = .04), and a BrainAGE index 0.77 years older (95% CI, 0.02-1.51 years; P = .05) at age 45 years. There were no statistically significant associations between blood lead level and log-transformed white matter hyperintensity volume (b = 0.05 log mm3; 95% CI, -0.02 to 0.13 log mm3; P = .17) or mean cortical thickness (b = -0.004 mm; 95% CI, -0.012 to 0.004 mm; P = .39). Each 5-μg/dL higher childhood blood lead level was significantly associated with a 2.07-point lower IQ score at age 45 years (95% CI, -3.39 to -0.74; P = .002) and a 0.12-point higher score on informant-rated cognitive problems (95% CI, 0.01-0.23; P = .03). There was no statistically significant association between childhood blood lead levels and self-reported cognitive problems (b = -0.02 points; 95% CI, -0.10 to 0.07; P = .68)., Conclusions and Relevance: In this longitudinal cohort study with a median 34-year follow-up, higher childhood blood lead level was associated with differences in some MRI measures of brain structure that suggested lower structural brain integrity in midlife. Because of the large number of statistical comparisons, some findings may represent type I error.

DNA methylation plays an important role in both normal human development and risk of disease. The most utilized method of assessing DNA methylation uses BeadChips, generating an epigenome-wide "snapshot" of >450,000 observations (probe measurements) per assay. However, the reliability of each of these measurements is not equal, and little consideration is paid to consequences for research. We correlated repeat measurements of the same DNA samples using the Illumina HumanMethylation450K and the Infinium MethylationEPIC BeadChips in 350 blood DNA samples. Probes that were reliably measured were more heritable and showed consistent associations with environmental exposures, gene expression, and greater cross-tissue concordance. Unreliable probes were less replicable and generated an unknown volume of false negatives. This serves as a lesson for working with DNA methylation data, but the lessons are equally applicable to working with other data: as we advance toward generating increasingly greater volumes of data, failure to document reliability risks harming reproducibility., Competing Interests: Declaration of Interests The authors declare no competing interests.

Importance: Mental health professionals typically encounter patients at 1 point in patients' lives. This cross-sectional window understandably fosters focus on the current presenting diagnosis. Research programs, treatment protocols, specialist clinics, and specialist journals are oriented to presenting diagnoses, on the assumption that diagnosis informs about causes and prognosis. This study tests an alternative hypothesis: people with mental disorders experience many different kinds of disorders across diagnostic families, when followed for 4 decades., Objective: To describe mental disorder life histories across the first half of the life course., Design, Setting, and Participants: This cohort study involved participants born in New Zealand from 1972 to 1973 who were enrolled in the population-representative Dunedin Study. Participants were observed from birth to age 45 years (until April 2019). Data were analyzed from May 2019 to January 2020., Main Outcomes and Measures: Diagnosed impairing disorders were assessed 9 times from ages 11 to 45 years. Brain function was assessed through neurocognitive examinations conducted at age 3 years, neuropsychological testing during childhood and adulthood, and midlife neuroimaging-based brain age., Results: Of 1037 original participants (535 male [51.6%]), 1013 had mental health data available. The proportions of participants meeting the criteria for a mental disorder were as follows: 35% (346 of 975) at ages 11 to 15 years, 50% (473 of 941) at age 18 years, 51% (489 of 961) at age 21 years, 48% (472 of 977) at age 26 years, 46% (444 of 969) at age 32 years, 45% (429 of 955) at age 38 years, and 44% (407 of 927) at age 45 years. The onset of the disorder occurred by adolescence for 59% of participants (600 of 1013), eventually affecting 86% of the cohort (869 of 1013) by midlife. By age 45 years, 85% of participants (737 of 869) with a disorder had accumulated comorbid diagnoses. Participants with adolescent-onset disorders subsequently presented with disorders at more past-year assessments (r = 0.71; 95% CI, 0.68 to 0.74; P < .001) and met the criteria for more diverse disorders (r = 0.64; 95% CI, 0.60 to 0.67; P < .001). Confirmatory factor analysis summarizing mental disorder life histories across 4 decades identified a general factor of psychopathology, the p-factor. Longitudinal analyses showed that high p-factor scores (indicating extensive mental disorder life histories) were antedated by poor neurocognitive functioning at age 3 years (r = -0.18; 95% CI, -0.24 to -0.12; P < .001), were accompanied by childhood-to-adulthood cognitive decline (r = -0.11; 95% CI, -0.17 to -0.04; P < .001), and were associated with older brain age at midlife (r = 0.14; 95% CI, 0.07 to 0.20; P < .001)., Conclusions and Relevance: These findings suggest that mental disorder life histories shift among different successive disorders. Data from the present study, alongside nationwide data from Danish health registers, inform a life-course perspective on mental disorders. This perspective cautions against overreliance on diagnosis-specific research and clinical protocols.

Health and social scientists have documented the hospital revolving-door problem, the concentration of crime, and long-term welfare dependence. Have these distinct fields identified the same citizens? Using administrative databases linked to 1.7 million New Zealanders, we quantified and monetized inequality in distributions of health and social problems and tested whether they aggregate within individuals. Marked inequality was observed: Gini coefficients equalled 0.96 for criminal convictions, 0.91 for public-hospital nights, 0.86 for welfare benefits, 0.74 for prescription-drug fills and 0.54 for injury-insurance claims. Marked aggregation was uncovered: a small population segment accounted for a disproportionate share of use-events and costs across multiple sectors. These findings were replicated in 2.3 million Danes. We then integrated the New Zealand databases with the four-decade-long Dunedin Study. The high-need/high-cost population segment experienced early-life factors that reduce workforce readiness, including low education and poor mental health. In midlife they reported low life satisfaction. Investing in young people's education and training potential could reduce health and social inequalities and enhance population wellbeing.

Young people's life chances can be predicted by characteristics of their neighbourhood 1 . Children growing up in disadvantaged neighbourhoods exhibit worse physical and mental health and suffer poorer educational and economic outcomes than children growing up in advantaged neighbourhoods. Increasing recognition that aspects of social inequalities tend, in fact, to be geographical inequalities 2-5 is stimulating research and focusing policy interest on the role of place in shaping health, behaviour and social outcomes. Where neighbourhood effects are causal, neighbourhood-level interventions can be effective. Where neighbourhood effects reflect selection of families with different characteristics into different neighbourhoods, interventions should instead target families or individuals directly. To test how selection may affect different neighbourhood-linked problems, we linked neighbourhood data with genetic, health and social outcome data for >7,000 European-descent UK and US young people in the E-Risk and Add Health studies. We tested selection/concentration of genetic risks for obesity, schizophrenia, teen pregnancy and poor educational outcomes in high-risk neighbourhoods, including genetic analysis of neighbourhood mobility. Findings argue against genetic selection/concentration as an explanation for neighbourhood gradients in obesity and mental health problems. By contrast, modest genetic selection/concentration was evident for teen pregnancy and poor educational outcomes, suggesting that neighbourhood effects for these outcomes should be interpreted with care.

Children who grow up in neighborhoods with more green vegetation show enhanced cognitive development in specific domains over short timespans. However, it is unknown if neighborhood greenery per se is uniquely predictive of children's overall cognitive development measured across many years. The E-Risk Longitudinal Study, a nationally representative 1994-5 birth-cohort of children in Britain (n = 1658 urban and suburban-dwelling participants), was used to test whether residential neighborhood greenery uniquely predicts children's cognitive development across childhood and adolescence. Greenery exposure was assessed from ages 5 to 18 using the satellite imagery-based normalized difference vegetation index (NDVI) in 1-mile buffers around the home. Fluid and crystalized intellectual performance was assessed in the home at ages 5, 12, and 18 using the Wechsler Intelligence Scale, and executive function, working memory, and attention ability were assessed in the home at age 18 using the Cambridge Neuropsychological Test Automated Battery. Children living in residences surrounded by more neighborhood greenery scored significantly higher, on average, on IQ measures at all ages. However, the association between greenery and cognitive measures did not hold after accounting for family or neighborhood socioeconomic status. After adjustment for study covariates, child greenery exposure was not a significant predictor of longitudinal increases in IQ across childhood and adolescence or of executive function, working memory, or attention ability at age 18. Children raised in greener neighborhoods exhibit better overall cognitive ability, but the association is likely accounted for by family and neighborhood socioeconomic factors., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Victimized adolescents have an increased risk of self-injurious thoughts and behaviors. However, poor understanding of causal and non-causal mechanisms underlying this observed risk limits the development of interventions to prevent premature death in adolescents. This study tested whether pre-existing family-wide and individual vulnerabilities account for victimized adolescents' increased risk of self-injurious thoughts and behaviors., Method: Participants were 2,232 British children followed from birth to 18 years of age as part of the Environmental Risk Longitudinal Twin Study. Adolescent victimization (maltreatment, neglect, sexual victimization, family violence, peer/sibling victimization, cyber victimization, and crime victimization) was assessed through interviews with participants and co-informant questionnaires at the 18-year assessment. Suicidal ideation, self-harm, and suicide attempt in adolescence were assessed through interviews with participants at 18 years., Results: Victimized adolescents had an increased risk of suicidal ideation (odds ratio [OR] 2.40, 95% CI 2.11-2.74), self-harm (OR 2.38, 95% CI 2.10-2.69), and suicide attempt (OR 3.14, 95% CI 2.54-3.88). Co-twin control and propensity score matching analyses showed that these associations were largely accounted for by pre-existing familial and individual vulnerabilities, respectively. Over and above their prior vulnerabilities, victimized adolescents still showed a modest increase in risk for suicidal ideation (OR 1.45, 95%CI 1.10-1.91) and self-harm (OR 1.50, 95% CI 1.18-1.91) but not for suicide attempt (OR 1.28, 95% CI 0.83-1.98)., Conclusion: Risk for self-injurious thoughts and behaviors in victimized adolescents is explained only in part by the experience of victimization. Pre-existing vulnerabilities account for a large proportion of the risk. Therefore, effective interventions to prevent premature death in victimized adolescents should not only target the experience of victimization but also address pre-existing vulnerabilities., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: Millions of adults now entering middle age were exposed to high levels of lead, a developmental neurotoxin, as children. Although childhood lead exposure has been linked to disrupted behavioral development, the long-term consequences for adult mental and behavioral health have not been fully characterized., Objective: To examine whether childhood lead exposure is associated with greater psychopathology across the life course and difficult adult personality traits., Design, Setting, and Participants: This prospective cohort study was based on a population-representative birth cohort of individuals born between April 1, 1972, and March 31, 1973, in Dunedin, New Zealand, the Dunedin Multidisciplinary Health and Development Study. Members were followed up in December 2012 when they were 38 years of age. Data analysis was performed from March 14, 2018, to October 24, 2018., Exposures: Childhood lead exposure ascertained as blood lead levels measured at 11 years of age. Blood lead levels were unrelated to family socioeconomic status., Main Outcomes and Measures: Primary outcomes were adult mental health disorder symptoms assessed through clinical interview at 18, 21, 26, 32, and 38 years of age and transformed through confirmatory factor analysis into continuous measures of general psychopathology and internalizing, externalizing, and thought disorder symptoms (all standardized to a mean [SD] of 100 [15]) and adult personality assessed through informant report using the Big Five Personality Inventory (assessing neuroticism, extraversion, openness to experience, agreeableness, and conscientiousness) at 26, 32, and 38 years of age (all scores standardized to a mean [SD] of 0 [1]). Hypotheses were formulated after data collection; an analysis plan was posted in advance., Results: Of 1037 original study members, 579 (55.8%) were tested for lead exposure at 11 years of age (311 [53.7%] male). The mean (SD) blood lead level was 11.08 (4.96) μg/dL. After adjusting for study covariates, each 5-μg/dL increase in childhood blood lead level was associated with a 1.34-point increase (95% CI, 0.11-2.57; P = .03) in general psychopathology, driven by internalizing (b = 1.41; 95% CI, 0.19-2.62; P = .02) and thought disorder (b = 1.30; 95% CI, 0.06-2.54; P = .04) symptoms. Each 5-μg/dL increase in childhood blood lead level was also associated with a 0.10-SD increase in neuroticism (95% CI, 0.02-0.08; P = .02), a 0.09-SD decrease in agreeableness (95% CI, -0.18 to -0.01; P = .03), and a 0.14-SD decrease in conscientiousness (95% CI, -0.25 to -0.03; P = .01). There were no statistically significant associations with informant-rated extraversion (b = -0.09; 95% CI, -0.17 to 0.004; P = .06) and openness to experience (b = -0.07; 95% CI, -0.17 to 0.03; P = .15)., Conclusions and Relevance: In this multidecade, longitudinal study of lead-exposed children, higher childhood blood lead level was associated with greater psychopathology across the life course and difficult adult personality traits. Childhood lead exposure may have long-term consequences for adult mental health and personality.

Objective: Self-harm is associated with violent offending. However, little is known about young people who engage in "dual-harm" behavior. The authors investigated antecedents, clinical features, and life characteristics distinguishing dual-harming adolescents from those who self-harm only., Methods: Participants were from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative U.K. cohort of 2,232 twins born in 1994 and 1995. Self-harm in adolescence was assessed through interviews at age 18. Violent offending was assessed using a computer questionnaire at age 18 and police records through age 22. Risk factors were assessed between ages 5 and 12. Adolescent mental health, victimization, personality functioning, and use of support services were measured at age 18., Results: Self-harm was associated with violent crime (odds ratio=3.50, 95% CI=2.61-4.70), even after accounting for familial risk factors. Dual harmers had been victims of violence from childhood and exhibited lower childhood self-control and lower childhood IQ than self-only harmers. Dual harmers experienced higher rates of concurrent psychotic symptoms and substance dependence. They also exhibited distinct personality styles characterized by resistance to change and by emotional and interpersonal lability. However, dual harmers were not more likely than self-only harmers to have contact with mental health services., Conclusions: Dual harmers have self-control difficulties and are immersed in violence from a young age. A treatment- rather than punishment-oriented approach is indicated to meet these individuals' needs. Connecting self-harming adolescents with delinquency-reduction programs and transdiagnostic approaches that target self-regulation may reduce harmful behaviors. Preventing childhood maltreatment and implementing strategies to reduce victimization exposure could mitigate risk for both internalized and externalized violence.

Large-scale epigenome-wide association meta-analyses have identified multiple 'signatures'' of smoking. Drawing on these findings, we describe the construction of a polyepigenetic DNA methylation score that indexes smoking behavior and that can be utilized for multiple purposes in population health research. To validate the score, we use data from two birth cohort studies: The Dunedin Longitudinal Study, followed to age-38 years, and the Environmental Risk Study, followed to age-18 years. Longitudinal data show that changes in DNA methylation accumulate with increased exposure to tobacco smoking and attenuate with quitting. Data from twins discordant for smoking behavior show that smoking influences DNA methylation independently of genetic and environmental risk factors. Physiological data show that changes in DNA methylation track smoking-related changes in lung function and gum health over time. Moreover, DNA methylation changes predict corresponding changes in gene expression in pathways related to inflammation, immune response, and cellular trafficking. Finally, we present prospective data about the link between adverse childhood experiences (ACEs) and epigenetic modifications; these findings document the importance of controlling for smoking-related DNA methylation changes when studying biological embedding of stress in life-course research. We introduce the polyepigenetic DNA methylation score as a tool both for discovery and theory-guided research in epigenetic epidemiology.

Background: Childhood risk factors are associated with elevated inflammatory biomarkers in adulthood, but it is unknown whether these risk factors are associated with increased adult levels of the chronic inflammation marker soluble urokinase plasminogen activator receptor (suPAR). We aimed to test the hypothesis that childhood exposure to risk factors for adult disease is associated with elevated suPAR in adulthood and to compare suPAR with the oft-reported inflammatory biomarker C-reactive protein (CRP)., Methods: Prospective study of a population-representative 1972-1973 birth cohort; the Dunedin Multidisciplinary Health and Development Study observed participants to age 38 years. Main childhood predictors were poor health, socioeconomic disadvantage, adverse childhood experiences (ACEs), low IQ, and poor self-control. Main adult outcomes were adulthood inflammation measured as suPAR and high-sensitivity CRP (hsCRP)., Results: Participants with available plasma samples at age 38 were included (N = 837, 50.5% male). suPAR (mean 2.40 ng/ml; SD 0.91) was positively correlated with hsCRP (r 0.15, p < .001). After controlling for sex, body mass index (BMI), and smoking, children who experienced more ACEs, lower IQ, or had poorer self-control showed elevated adult suPAR. When the five childhood risks were aggregated into a Cumulative Childhood Risk index, and controlling for sex, BMI, and smoking, Cumulative Childhood Risk was associated with higher suPAR (b 0.10; SE 0.03; p = .002). Cumulative Childhood Risk predicted elevated suPAR, after controlling for hsCRP (b 0.18; SE 0.03; p < .001)., Conclusions: Exposure to more childhood risk factors was associated with higher suPAR levels, independent of CRP. suPAR is a useful addition to studies connecting childhood risk to adult inflammatory burden., (© 2018 Association for Child and Adolescent Mental Health.)

Background: Children with conduct problems that persist into adulthood are at increased risk for future behavioral, health, and social problems. However, the longer term public service usage among these children has not been fully documented. To aid public health and intervention planning, adult service usage across criminal justice, health care, and social welfare domains is compared among all individuals from a representative cohort who followed different conduct problem trajectories from childhood into adulthood., Methods: Participants are from the Dunedin Multidisciplinary Health and Development Study, a prospective, representative cohort of consecutive births (N = 1,037) from April 1972 to March 1973 in Dunedin, New Zealand. Regression analyses were used to compare levels of public service usage up to age 38, gathered via administrative and electronic medical records, between participants who displayed distinct subtypes of childhood conduct problems (low, childhood-limited, adolescent-onset, and life-course persistent)., Results: Children exhibiting life-course persistent conduct problems used significantly more services as adults than those with low levels of childhood conduct problems. Although this group comprised only 9.0% of the population, they accounted for 53.3% of all convictions, 15.7% of emergency department visits, 20.5% of prescription fills, 13.1% of injury claims, and 24.7% of welfare benefit months. Half of this group (50.0%) also accrued high service use across all three domains of criminal justice, health, and social welfare services, as compared to only 11.3% of those with low conduct problems (OR = 7.27, 95% CI = 4.42-12.0)., Conclusions: Conduct problems in childhood signal high future costs in terms of service utilization across multiple sectors. Future evaluations of interventions aimed at conduct problems should also track potential reductions in health burden and service usage that stretch into midlife., (© 2017 Association for Child and Adolescent Mental Health.)

Importance: Lead is a neurotoxin with well-documented effects on health. Research suggests that lead may be associated with criminal behavior. This association is difficult to disentangle from low socioeconomic status, a factor in both lead exposure and criminal offending., Objective: To test the hypothesis that a higher childhood blood lead level (BLL) is associated with greater risk of criminal conviction, recidivism (repeat conviction), conviction for violent offenses, and variety of self-reported criminal offending in a setting where BLL was not associated with low socioeconomic status., Design, Setting, and Participants: A total of 553 individuals participated in a prospective study based on a population-representative cohort born between April 1, 1972, and March 31, 1973, from New Zealand; the Dunedin Multidisciplinary Health and Development Study observed participants to age 38 years (December 2012). Statistical analysis was performed from November 10, 2016, to September 5, 2017., Exposures: Blood lead level measured at age 11 years., Main Outcomes and Measures: Official criminal conviction cumulative to age 38 years (data collected in 2013), single conviction or recidivism, conviction for nonviolent or violent crime, and self-reported variety of crime types at ages 15, 18, 21, 26, 32, and 38 years., Results: Participants included 553 individuals (255 female and 298 male participants) who had their blood tested for lead at age 11 years. The mean (SD) BLL at age 11 years was 11.01 (4.62) μg/dL. A total of 154 participants (27.8%) had a criminal conviction, 86 (15.6%) had recidivated, and 53 (9.6%) had a violent offense conviction. Variety scores for self-reported offending ranged from 0 to 10 offense types at each assessment; higher numbers indicated greater crime involvement. Self-reported offending followed the well-established age-crime curve (ie, the mean [SD] variety of self-reported offending increased from 1.99 [2.82] at age 15 years to its peak of 4.24 [3.15] at age 18 years and 4.22 [3.02] at age 21 years and declined thereafter to 1.10 [1.59] at age 38 years). Blood lead level was a poor discriminator between no conviction and conviction (area under the curve, 0.58). Overall, associations between BLL and conviction outcomes were weak. The estimated effect of BLL was lower for recidivism than for single convictions and lower for violent offending than for nonviolent offending. Sex-adjusted associations between BLL reached statistical significance for only 1 of the 6 self-reported offending outcomes at age 15 years (r = 0.10; 95% CI, 0.01-0.18; P = .02)., Conclusions and Relevance: This study overcomes past limitations of studies of BLL and crime by studying the association in a place and time where the correlation was not confounded by childhood socioeconomic status. Findings failed to support a dose-response association between BLL and consequential criminal offending.

Importance: Many children in the United States and around the world are exposed to lead, a developmental neurotoxin. The long-term cognitive and socioeconomic consequences of lead exposure are uncertain., Objective: To test the hypothesis that childhood lead exposure is associated with cognitive function and socioeconomic status in adulthood and with changes in IQ and socioeconomic mobility between childhood and midlife., Design, Setting, and Participants: A prospective cohort study based on a population-representative 1972-1973 birth cohort from New Zealand; the Dunedin Multidisciplinary Health and Development Study observed participants to age 38 years (until December 2012)., Exposures: Childhood lead exposure ascertained as blood lead levels measured at age 11 years. High blood lead levels were observed among children from all socioeconomic status levels in this cohort., Main Outcomes and Measures: The IQ (primary outcome) and indexes of Verbal Comprehension, Perceptual Reasoning, Working Memory, and Processing Speed (secondary outcomes) were assessed at age 38 years using the Wechsler Adult Intelligence Scale-IV (WAIS-IV; IQ range, 40-160). Socioeconomic status (primary outcome) was assessed at age 38 years using the New Zealand Socioeconomic Index-2006 (NZSEI-06; range, 10 [lowest]-90 [highest])., Results: Of 1037 original participants, 1007 were alive at age 38 years, of whom 565 (56%) had been lead tested at age 11 years (54% male; 93% white). Mean (SD) blood lead level at age 11 years was 10.99 (4.63) µg/dL. Among blood-tested participants included at age 38 years, mean WAIS-IV score was 101.16 (14.82) and mean NZSEI-06 score was 49.75 (17.12). After adjusting for maternal IQ, childhood IQ, and childhood socioeconomic status, each 5-µg/dL higher level of blood lead in childhood was associated with a 1.61-point lower score (95% CI, -2.48 to -0.74) in adult IQ, a 2.07-point lower score (95% CI, -3.14 to -1.01) in perceptual reasoning, and a 1.26-point lower score (95% CI, -2.38 to -0.14) in working memory. Associations of childhood blood lead level with deficits in verbal comprehension and processing speed were not statistically significant. After adjusting for confounders, each 5-µg/dL higher level of blood lead in childhood was associated with a 1.79-unit lower score (95% CI, -3.17 to -0.40) in socioeconomic status. An association between greater blood lead levels and a decline in IQ and socioeconomic status from childhood to adulthood was observed with 40% of the association with downward mobility mediated by cognitive decline from childhood., Conclusions and Relevance: In this cohort born in New Zealand in 1972-1973, childhood lead exposure was associated with lower cognitive function and socioeconomic status at age 38 years and with declines in IQ and with downward social mobility. Childhood lead exposure may have long-term ramifications.

Purpose: To describe official adult-onset offenders, investigate their antisocial histories and test hypotheses about their origins., Methods: We defined adult-onset offenders among 931 Dunedin Study members followed to age 38, using criminal-court conviction records., Results: Official adult-onset offenders were 14% of men, and 32% of convicted men, but accounted for only 15% of convictions. As anticipated by developmental theories emphasizing early-life influences on crime, adult-onset offenders' histories of antisocial behavior spanned back to childhood. Relative to juvenile-offenders, during adolescence they had fewer delinquent peers and were more socially inhibited, which may have protected them from conviction. As anticipated by theories emphasizing the importance of situational influences on offending, adult-onset offenders, relative to non-offenders, during adulthood more often had schizophrenia, bipolar disorder, and alcohol-dependence, had weaker social bonds, anticipated fewer informal sanctions, and self-reported more offenses. Contrary to some expectations, adult-onset offenders did not have high IQ or high socioeconomic-status families protecting them from juvenile conviction., Conclusions: A tailored theory for adult-onset offenders is unwarranted because few people begin crime de novo as adults. Official adult-onset offenders fall on a continuum of crime and its correlates, between official non-offenders and official juvenile-onset offenders. Existing theories can accommodate adult-onset offenders.

Policy-makers are interested in early-years interventions to ameliorate childhood risks. They hope for improved adult outcomes in the long run, bringing return on investment. How much return can be expected depends, partly, on how strongly childhood risks forecast adult outcomes. But there is disagreement about whether childhood determines adulthood. We integrated multiple nationwide administrative databases and electronic medical records with the four-decade Dunedin birth-cohort study to test child-to-adult prediction in a different way, by using a population-segmentation approach. A segment comprising one-fifth of the cohort accounted for 36% of the cohort's injury insurance-claims; 40% of excess obese-kilograms; 54% of cigarettes smoked; 57% of hospital nights; 66% of welfare benefits; 77% of fatherless childrearing; 78% of prescription fills; and 81% of criminal convictions. Childhood risks, including poor age-three brain health, predicted this segment with large effect sizes. Early-years interventions effective with this population segment could yield very large returns on investment.

There is evidence that persistent psychiatric disorders lead to age-related disease and premature mortality. Telomere length has emerged as a promising biomarker in studies that test the hypothesis that internalizing psychiatric disorders are associated with accumulating cellular damage. We tested the association between the persistence of internalizing disorders (depression, generalized anxiety disorder and post-traumatic stress disorder) and leukocyte telomere length (LTL) in the prospective longitudinal Dunedin Study (n=1037). Analyses showed that the persistence of internalizing disorders across repeated assessments from ages 11 to 38 years predicted shorter LTL at age 38 years in a dose-response manner, specifically in men (β=-0.137, 95% confidence interval (CI): -0.232, -0.042, P=0.005). This association was not accounted for by alternative explanatory factors, including childhood maltreatment, tobacco smoking, substance dependence, psychiatric medication use, poor physical health or low socioeconomic status. Additional analyses using DNA from blood collected at two time points (ages 26 and 38 years) showed that LTL erosion was accelerated among men who were diagnosed with internalizing disorder in the interim (β=-0.111, 95% CI: -0.184, -0.037, P=0.003). No significant associations were found among women in any analysis, highlighting potential sex differences in internalizing-related telomere biology. These findings point to a potential mechanism linking internalizing disorders to accelerated biological aging in the first half of the life course, particularly in men. Because internalizing disorders are treatable, the findings suggest the hypothesis that treating psychiatric disorders in the first half of the life course may reduce the population burden of age-related disease and extend health expectancy.

Background: We examine prospectively the influence of two separate but potentially inter-related factors in the etiology of post-traumatic stress disorder (PTSD): childhood maltreatment as conferring a susceptibility to the PTSD response to adult trauma and juvenile disorders as precursors of adult PTSD., Method: The Dunedin Multidisciplinary Health and Development Study (DMHDS) is a birth cohort (n = 1037) from the general population of New Zealand's South Island, with multiple assessments up to age 38 years. DSM-IV PTSD was assessed among participants exposed to trauma at ages 26-38. Complete data were available on 928 participants., Results: Severe maltreatment in the first decade of life, experienced by 8.5% of the sample, was associated significantly with the risk of PTSD among those exposed to adult trauma [odds ratio (OR) 2.64, 95% confidence interval (CI) 1.16-6.01], compared to no maltreatment. Moderate maltreatment, experienced by 27.2%, was not associated significantly with that risk (OR 1.55, 95% CI 0.85-2.85). However, the two estimates did not differ significantly from one another. Juvenile disorders (ages 11-15), experienced by 35% of the sample, independent of childhood maltreatment, were associated significantly with the risk of PTSD response to adult trauma (OR 2.35, 95% CI 1.32-4.18)., Conclusions: Severe maltreatment is associated with risk of PTSD response to adult trauma, compared to no maltreatment, and juvenile disorders, independent of earlier maltreatment, are associated with that risk. The role of moderate maltreatment remains unresolved. Larger longitudinal studies are needed to assess the impact of moderate maltreatment, experienced by the majority of adult trauma victims with a history of maltreatment.

Mental disorders traditionally have been viewed as distinct, episodic, and categorical conditions. This view has been challenged by evidence that many disorders are sequentially comorbid, recurrent/chronic, and exist on a continuum. Using the Dunedin Multidisciplinary Health and Development Study, we examined the structure of psychopathology, taking into account dimensionality, persistence, co-occurrence, and sequential comorbidity of mental disorders across 20 years, from adolescence to midlife. Psychiatric disorders were initially explained by three higher-order factors (Internalizing, Externalizing, and Thought Disorder) but explained even better with one General Psychopathology dimension. We have called this dimension the p factor because it conceptually parallels a familiar dimension in psychological science: the g factor of general intelligence. Higher p scores are associated with more life impairment, greater familiality, worse developmental histories, and more compromised early-life brain function. The p factor explains why it is challenging to find causes, consequences, biomarkers, and treatments with specificity to individual mental disorders. Transdiagnostic approaches may improve research.

Why do more intelligent people live healthier and longer lives? One possibility is that intelligence tests assess health of the brain, but psychological science has lacked technology to evaluate this hypothesis. Digital retinal imaging, a new, noninvasive method to visualize microcirculation in the eye, may reflect vascular conditions in the brain. We studied the association between retinal vessel caliber and neuropsychological functioning in the representative Dunedin birth cohort. Wider venular caliber was associated with poorer neuropsychological functioning at midlife, independently of potentially confounding factors. This association was not limited to any specific test domain and extended to informants' reports of cohort members' cognitive difficulties in everyday life. Moreover, wider venular caliber was associated with lower childhood IQ tested 25 years earlier. The findings indicate that retinal venular caliber may be an indicator of neuropsychological health years before the onset of dementing diseases and suggest that digital retinal imaging may be a useful investigative tool for psychological science.

There is increasing interest in discovering mechanisms that mediate the effects of childhood stress on late-life disease morbidity and mortality. Previous studies have suggested one potential mechanism linking stress to cellular aging, disease and mortality in humans: telomere erosion. We examined telomere erosion in relation to children's exposure to violence, a salient early-life stressor, which has known long-term consequences for well-being and is a major public-health and social-welfare problem. In the first prospective-longitudinal study with repeated telomere measurements in children while they experienced stress, we tested the hypothesis that childhood violence exposure would accelerate telomere erosion from age 5 to age 10 years. Violence was assessed as exposure to maternal domestic violence, frequent bullying victimization and physical maltreatment by an adult. Participants were 236 children (49% females; 42% with one or more violence exposures) recruited from the Environmental-Risk Longitudinal Twin Study, a nationally representative 1994-1995 birth cohort. Each child's mean relative telomere length was measured simultaneously in baseline and follow-up DNA samples, using the quantitative PCR method for T/S ratio (the ratio of telomere repeat copy numbers to single-copy gene numbers). Compared with their counterparts, the children who experienced two or more kinds of violence exposure showed significantly more telomere erosion between age-5 baseline and age-10 follow-up measurements, even after adjusting for sex, socioeconomic status and body mass index (B=-0.052, s.e.=0.021, P=0.015). This finding provides support for a mechanism linking cumulative childhood stress to telomere maintenance, observed already at a young age, with potential impact for life-long health.

Objectives: To test whether frequent bullying victimisation in childhood increases the likelihood of self harming in early adolescence, and to identify which bullied children are at highest risk of self harm., Design: The Environmental Risk (E-Risk) longitudinal study of a nationally representative UK cohort of 1116 twin pairs born in 1994-95 (2232 children)., Setting: England and Wales, United Kingdom., Participants: Children assessed at 5, 7, 10, and 12 years of age., Main Outcome Measures: Relative risks of children's self harming behaviour in the six months before their 12th birthday., Results: Self harm data were available for 2141 children. Among children aged 12 who had self harmed (2.9%; n=62), more than half were victims of frequent bullying (56%; n=35). Exposure to frequent bullying predicted higher rates of self harm even after children's pre-morbid emotional and behavioural problems, low IQ, and family environmental risks were taken into account (bullying victimisation reported by mother: adjusted relative risk 1.92, 95% confidence interval 1.18 to 3.12; bullying victimisation reported by child: 2.44, 1.36 to 4.40). Victimised twins were more likely to self harm than were their non-victimised twin sibling (bullying victimisation reported by mother: 13/162 v 3/162, ratio=4.3, 95% confidence interval 1.3 to 14.0; bullying victimisation reported by child: 12/144 v 7/144, ratio=1.7, 0.71 to 4.1). Compared with bullied children who did not self harm, bullied children who self harmed were distinguished by a family history of attempted/completed suicide, concurrent mental health problems, and a history of physical maltreatment by an adult., Conclusions: Prevention of non-suicidal self injury in young adolescents should focus on helping bullied children to cope more appropriately with their distress. Programmes should target children who have additional mental health problems, have a family history of attempted/completed suicide, or have been maltreated by an adult.

Study Objectives: To examine concurrent associations between maternal insomnia and different aspects of the family socialization environment., Design: Mothers reported on their symptoms of insomnia in a private standardized interview and interviewers evaluated the family socialization environment using the Coder's Inventory., Setting: Assessments were conducted in participants' homes within the U.K., Patients or Participants: One thousand one hundred sixteen mothers of British children enrolled in the Environmental Risk (E-Risk) study were invited to participate when their children were aged 12 years., Interventions: N/A., Measurements and Results: After controlling for family socioeconomic status (SES), mothers' relationship status, and maternal depression, maternal insomnia was associated with a poorer family socialization environment (β = -0.10, [95% confidence intervals (CI) = -0.16, -0.04], P < 0.001). When family socialization environment subscales were examined, after controlling for family SES, mothers' relationship status, and maternal depression, maternal insomnia was associated with greater chaos (β = 0.09, [95% CI = 0.03, 0.15], P = 0.002), greater child neglect (β = 0.13, [95% CI = 0.07, 0.18], P < 0.001), less happiness (β = -0.13, [95% CI = -0.18, -0.07], P < 0.001), less child stimulation (β = -0.06, [95% CI = -0.11, 0.00], P = 0.043), but not poorer state of the home, such as orderliness (β = -0.04, [95% CI = -0.10, 0.02], P = 0.182)., Conclusions: Maternal insomnia is associated with the family socialization environment. This finding emphasizes the need to consider insomnia in the family context.

Pubertal development is a nonlinear process progressing from prepubescent beginnings through biological, physical, and psychological changes to full sexual maturity. To tether theoretical concepts of puberty with sophisticated longitudinal, analytical models capable of articulating pubertal development more accurately, we used nonlinear mixed-effects models to describe both the timing and tempo of pubertal development in the sample of 364 White boys and 373 White girls measured across 6 years as part of the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development. Individual differences in timing and tempo were extracted with models of logistic growth. Differential relations emerged for how boys' and girls' timing and tempo of development were related to physical characteristics (body mass index, height, and weight) and psychological outcomes (internalizing problems, externalizing problems, and risky sexual behavior). Timing and tempo are associated in boys but not girls. Pubertal timing and tempo are particularly important for predicting psychological outcomes in girls but only sparsely related to boys' psychological outcomes. Results highlight the importance of considering the nonlinear nature of puberty and expand the repertoire of possibilities for examining important aspects of how and when pubertal processes contribute to development.

Teaching children requires effort, and some children naturally require more effort than others. In this study, we tested whether teacher effort devoted to individual children varies as a function of each child's personal characteristics. In a nationwide longitudinal study of 1,102 pairs of twins followed for 7 years, between the ages of 5 and 12 years, we asked teachers about the effort they invested in each child in our study. We found that teacher effort was a function of heritable child characteristics, that a child's challenging behavior assessed at 5 years of age predicted teacher effort toward the same child at 12 years of age, and that challenging child behavior and teacher effort share a common etiology with respect to children's genes. We found that child effects accounted for a significant proportion of variance in teacher effort, but also observed variation in effort exerted by teachers that could not be attributed to children's behavior. Treating children who exhibit challenging behavior and enhancing teachers' skills in managing such behavior could increase the time and energy teachers have to deliver their curriculum in class.

Life-history theories of the early programming of human reproductive strategy stipulate that early rearing experience, including that reflected in infant-parent attachment security, regulates psychological, behavioral, and reproductive development. We tested the hypothesis that infant attachment insecurity, compared with infant attachment security, at the age of 15 months predicts earlier pubertal maturation. Focusing on 373 White females enrolled in the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development, we gathered data from annual physical exams from the ages of 9½ years to 15½ years and from self-reported age of menarche. Results revealed that individuals who had been insecure infants initiated and completed pubertal development earlier and had an earlier age of menarche compared with individuals who had been secure infants, even after accounting for age of menarche in the infants' mothers. These results support a conditional-adaptational view of individual differences in attachment security and raise questions about the biological mechanisms responsible for the attachment effects we discerned.

Context: Decreased physical activity plays a critical role in the increase in childhood obesity. Although at least 60 minutes per day of moderate-to-vigorous physical activity (MVPA) is recommended, few longitudinal studies have determined the recent patterns of physical activity of youth., Objective: To determine the patterns and determinants of MVPA of youth followed from ages 9 to 15 years., Design, Setting, and Participants: Longitudinal descriptive analyses of the 1032 participants in the 1991-2007 National Institute of Child Health and Human Development Study of Early Child Care and Youth Development birth cohort from 10 study sites who had accelerometer-determined minutes of MVPA at ages 9 (year 2000), 11 (2002), 12 (2003), and 15 (2006) years. Participants included boys (517 [50.1%]) and girls (515 [49.9%]); 76.6% white (n = 791); and 24.5% (n = 231) lived in low-income families., Main Outcome Measure: Mean MVPA minutes per day, determined by 4 to 7 days of monitored activity., Results: At age 9 years, children engaged in MVPA approximately 3 hours per day on both weekends and weekdays. Weekday MVPA decreased by 37 minutes per year [corrected], while weekend MVPA decreased by 39 minutes per year [corrected]. By age 15 years, adolescents were only engaging in MVPA for 50 minutes per weekday [corrected] and 36 minutes per weekend day [corrected]. Boys were more active than girls, spending 18 and 14 more minutes per day [corrected] in MVPA on the weekdays and weekends, respectively. The rate of decrease in MVPA was the same for boys and girls. The estimated age at which girls crossed below the recommended 60 minutes of MVPA per day was approximately 13.2 years for weekday [corrected] activity compared with boys at 14.9 years [corrected], and for weekend activity, girls crossed below the recommended 60 minutes of MVPA at 12.7 years [corrected] compared with boys at 13.6 years [corrected]., Conclusion: In this study cohort, measured physical activity decreased significantly between ages 9 and 15 years.

We know that exposure to marital conflict places infants at risk, but we know less about processes. One process may be role reversal, when a distressed parent looks to the child to meet unmet needs for comfort, intimacy, or companionship. A parent in marital conflict may be particularly prone to role reversal, which in turn adversely affects child development. The current study examined pathways from infants' exposure to marital conflict at 12 months to role reversal at 24 months. We sampled low-middle socioeconomic status (SES) families with their first child (N = 128). Independent observers assessed marital conflict (in a problem-solving task) and role reversal (in a story-telling task). We found that each parent's conflict behavior predicted the other parent's role reversal. In a direct pathway, mother's conflict behavior towards father led directly to father's role reversal with the child. In an indirect pathway, father's conflict behavior towards mother led to his withdrawal from her, which in turn led to mother's role reversal with the child. Clinical implications are discussed within a developmental psychopathology framework in terms of preventive interventions to offset the deleterious effect of marital conflict and role reversal on child development., (Copyright © 2008 Michigan Association for Infant Mental Health.)

Objective: To investigate ecological correlates of the development of overweight in a multisite study sample of children followed from age 2 to 12., Design: Longitudinal examination of covariates of overweight status throughout childhood, with covariates drawn from three ecological levels: sociocultural or demographic, quality of the child's home environment, and proximal child experience that could directly affect the balance between energy intake and energy expenditure., Subjects: A total of 960 children participating in a long-term longitudinal study provided growth data at least once; 653 of the children had complete data on covariates., Measurements: Height and weight measured seven times between ages 2 and 12 were converted to a body mass index (BMI) and entered into a latent transition analysis to identify patterns of overweight across childhood. Ecological correlates measured longitudinally included demographic characteristics obtained by maternal report, home environment quality obtained by observation and maternal report, and proximal child experience factors obtained by observation, maternal report and child report., Results: Four patterns of overweight were found: never overweight, overweight beginning at preschool age, overweight beginning in elementary school, and return to normal weight after being overweight at preschool age. The weight status groups differed on home environment quality and proximal child experience factors but not on demographics. Children overweight at preschool had less sensitive mothers than never overweight children. Children overweight at school age had fewer opportunities for productive activity at home than did never overweight children. School-age overweight children also watched the most TV after school. Multivariate logistic regression analyses further indicated the significance to children's weight status of proximal child experience variables. Less physically active children and those who watched more television after school were more likely to become overweight. Results did not vary by child sex., Conclusion: The results support the idea that childhood overweight is multiply determined. The one potentially important and changeable factor identified as a target for intervention centers on how children spend their time, especially their after-school time. Children who are more physically active and spend less time watching TV after school are less likely to become overweight by age 12.

Two general evolutionary hypotheses were tested on 756 White children (397 girls) studied longitudinally: (1) rearing experiences would predict pubertal timing; and (2) children would prove differentially susceptible to rearing. Analysis of pubertal measurements, including some based on repeated physical assessments, showed that mothering and fathering, earlier and later in childhood, predicted pubertal development, but only for girls, with negative parenting appearing most influential; maternal harsh control predicted earlier menarche. Rearing effects varied by infant negative emotionality, proving stronger (and opposite) for girls who in infancy were lower rather than higher in negativity. Maternal menarche, controlled in all analyses, was a stronger predictor than rearing. Findings are discussed in terms of theory development, genetic and nutritional influences, and sample restrictions.

The current study examined the intergenerational transmission of role reversal within a developmental psychopathology framework. Role reversal is a relationship disturbance in which a parent looks to a child to meet the parent's need for comfort, parenting, intimacy, or play, and the child attempts to meet these needs. In a normative sample, n=138, fathers and mothers reported on childhood role reversal with their mothers as part of the Adult Attachment Interview, AAI (George, Kaplan, & Main, 1984). Mother-child role reversal was then assessed in an observational paradigm when children were 2 years of age. Based on theories of dyadic and family systems internal working models we hypothesized gender specific replications of role reversal in the next generation. Indeed, mothers who reported role reversal with their mothers during the AAI tended to engage in higher levels of role reversal with their toddler-aged daughters. Furthermore, when fathers reported role reversal with their mothers during the AAI, mothers tended to engage in higher levels of role reversal with their toddler-aged sons. The importance of the inclusion of fathers in family research, the relationship between role reversal and attachment, and implications for preventive interventions are discussed.