Publications
All peer reviewed publications are listed below.
Displaying page 3 of 24.
Childhood disadvantage and adolescent socioemotional wellbeing as predictors of future parenting behaviour | 2020
McAnally, H. M. Iosua, E. Sligo, J. L. Belsky, J. Spry,
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Journal of Adolescence, 2020, 86 90-100.
https://doi.org/10.1016/j.adolescence.2020.12.005
Link to full publication »
Our ref: RO749
INTRODUCTION: In extending work on early life antecedents of parenting, we investigate associations between childhood family history of disadvantage, adolescent socioemotional wellbeing, and age at first parenthood and subsequent parenting behaviour. METHODS: Parent-child interactions were recorded when participants in the longitudinal Dunedin Multidisciplinary Health and Development Study (New Zealand) had a three-year-old child. Data were available for 358 mothers and 321 fathers, aged between 17.7 and 41.5 at the time of their child's birth. Associations between parenting and antecedent data on socioeconomic disadvantage, adolescent wellbeing and mental health, as well as current adult mental health and age at parenting, were tested for using structural equation modelling. RESULTS: Family disadvantage in childhood and lower adolescent wellbeing was associated with less positive future parenting, but only adult (not adolescent) anxiety/depression symptoms were directly associated with parenting behaviour. Childhood family disadvantage was associated with further disadvantage across the life course that included less positive parenting of the next generation. In contrast, socioemotional wellbeing during adolescence and later age of onset of parenting were associated with more positive parenting. CONCLUSIONS: Reducing childhood disadvantage and improving socioemotional wellbeing during childhood and adolescence is likely to have intergenerational benefits through better parenting of the next generation.
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Intimate partner violence and lower relationship quality are associated with faster biological aging | 2020
Bourassa, K. J. Caspi, A. Harrington, H. Houts, R. Poulton,
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Psychology and Aging, 2020, 35(8), 1127-1139.
http://dx.doi.org/10.1037/pag0000581
Link to full publication »
Our ref: RO747
The characteristics of people's relationships have relevance to health-high quality romantic relationships are associated with improved health whereas intimate partner violence is associated with poorer health. Recently, increased attention has been focused on the biological processes underpinning these associations. A geroscience approach-examining whether close relationship characteristics are associated with biological aging-would complement previous research focused on individual disease pathways. This study used participants from the Dunedin Study (N = 974) to investigate relationship characteristics and biological aging across almost 20 years, from age 26 to 45. Being involved in romantic relationships was associated with slower biological aging, beta = -0.12, p < .001. This difference represented 2.9 years of aging over the two decades. Greater relationship quality was also associated with slower biological aging, beta = -0.19, p < .001, whereas higher levels of partner violence were associated with faster biological aging, beta = 0.25, p < .001. A 1 SD difference in these characteristics was associated with a difference of 1.0 and 1.3 years of aging over the two decades, respectively. Secondary analyses suggested that experiencing violence from a partner was more strongly associated with biological aging than perpetrating violence, and that the experience of physical violence was more strongly associated with aging than psychological violence. These findings suggest that the characteristics of romantic relationships have relevance for biological aging in midlife. Interventions designed to increase relationship quality and decrease partner violence could reduce future morbidity and early mortality by slowing people's biological aging. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
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Is cardiovascular fitness associated with structural brain integrity in midlife? Evidence from a population-representative birth cohort study | 2020
d'Arbeloff, T., Cooke, M., Knodt,
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Aging, 2020, 12(20), .
https://doi.org/10.18632/aging.104112
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Our ref: RO744
Improving cardiovascular fitness may buffer against age-related cognitive decline and mitigate dementia risk by staving off brain atrophy. However, it is unclear if such effects reflect factors operating in childhood (neuroselection) or adulthood (neuroprotection). Using data from 807 members of the Dunedin Study, a population-representative birth cohort, we investigated associations between cardiovascular fitness and structural brain integrity at age 45, and the extent to which associations reflected possible neuroselection or neuroprotection by controlling for childhood IQ. Higher fitness, as indexed by VO2Max, was not associated with average cortical thickness, total surface area, or subcortical gray matter volume including the hippocampus. However, higher fitness was associated with thicker cortex in prefrontal and temporal regions as well as greater cerebellar gray matter volume. Higher fitness was also associated with decreased hippocampal fissure volume. These associations were unaffected by the inclusion of childhood IQ in analyses. In contrast, a higher rate of decline in cardiovascular fitness from 26 to 45 years was not robustly associated with structural brain integrity. Our findings are consistent with a neuroprotective account of adult cardiovascular fitness but suggest that effects are not uniformly observed across the brain and reflect contemporaneous fitness more so than decline over time
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Association of childhood lead exposure with MRI measurements of structural brain integrity in midlife | 2020
Reuben, A. Elliott, M.L. Abraham, C. Broadbent, J. Houts,
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JAMA, 2020, 324(19), 1970-1979.
https://doi.org/10.1001/jama.2020.19998
Link to full publication »
Our ref: RO742
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).
Exposure. Childhood blood-lead levels measured at age 11 years.
Main Outcomes and Measures. Structural brain integrity at age 45 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)-100(diffusion is perfectly anisotropic)]), and 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). Age-45 cognitive function was assessed objectively via the Wechsler Adult Intelligence Scale–IV [IQ range, 40-160, standardized to mean(SD)=100(15)] and subjectively via informant and self-reports [z-score units, scale mean(SD)=0(1)].
Results. Of 1037 original participants, 997 were alive at age 45, of whom 564(57%) had received lead testing at age 11 years (302[54%] male) (median follow-up 34 years, IQR 33.7-34.7). Mean(SD) age-11 blood-lead level was 10.99(4.63) µg/dL. After adjusting for covariates, each 5µg/dL higher childhood blood-lead level was significantly associated with 1.19 cm2 smaller cortical surface area (95%CI:-2.35,-0.02, P=.05), 0.10 cm3 smaller hippocampal volume (95%CI:-0.17,-0.03, P=.006), lower global fractional anisotropy (b=-0.12, 95%CI:-0.24,-0.01, P=.04), and 0.77 years older brainAGE (95%CI:0.02, 1.51, P=.05). 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, 0.13, P=.17) or mean cortical thickness (b=-0.004 mm, 95%CI:-0.012, 0.004, P=.39). Each 5µg/dL higher childhood blood-lead level was significantly associated with a 2.07-point lower score (95%CI:-3.39,-0.74, P=.002) in age-45 IQ, and a 0.12-point higher score (95%CI:0.01, 0.23, P=.03) on informant-rated cognitive problems. There was no statistically significant association between childhood blood-lead levels and self-reported cognitive problems (b=-0.02 points, 95%CI: -0.10, 0.07, P=.68).
Conclusion 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 mid-life. Because of the large number of statistical comparisons, some findings may represent type I error.
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Patterns of Reliability: Assessing the Reproducibility and Integrity of DNA Methylation Measurement | 2020
Karen Sugden, Eilis J. Hannon, Louise Arseneault, Daniel W. Belsky, David L. Corcoran,
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Patterns, 2020, 1(2), .
https://doi.org/10.1016/j.patter.2020.100014
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Our ref: RO740
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.
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What is the test-retest reliability of common task-fMRI measures? New empirical evidence and a meta-analysis | 2020
Maxwell L. Elliott, Annchen R. Knodt, David Ireland, Meriwether L. Morris, Richie Poulton,
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Psychological Science, 2020, 31(7), .
https://doi.org/10.1177%2F0956797620916786
Our ref: RO734
Identifying brain biomarkers of disease risk is a growing priority in neuroscience. The ability to identify meaningful biomarkers is limited by measurement reliability; unreliable measures are unsuitable for predicting clinical outcomes. Measuring brain activity using task functional MRI (fMRI) is a major focus of biomarker development; however, the reliability of task fMRI has not been systematically evaluated. We present converging evidence demonstrating poor reliability of task-fMRI measures. First, a meta-analysis of 90 experiments (N = 1,008) revealed poor overall reliability—mean intraclass correlation coefficient (ICC) = .397. Second, the test-retest reliabilities of activity in a priori regions of interest across 11 common fMRI tasks collected by the Human Connectome Project (N = 45) and the Dunedin Study (N = 20) were poor (ICCs = .067–.485). Collectively, these findings demonstrate that common task-fMRI measures are not currently suitable for brain biomarker discovery or for individual-differences research. We review how this state of affairs came to be and highlight avenues for improving task-fMRI reliability.
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Identifying Adolescents at Risk for Depression: A Prediction Score Performance in Cohorts Based Q1Q2 in Three Different Continents | 2020
Thiago Botter-Maio Rocha, Helen L. Fisher, Arthur Caye, , Luciana Anselmi,
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Journal of the American Academy of Child & Adolescent Psychiatry, 2020, .
https://doi.org/10.1016/j.jaac.2019.12.004
Link to full publication »
Our ref: RO729
Objective: Prediction models have become frequent in the medical literature, but most published studies are conducted in a single setting. Heterogeneity between development and validation samples has been posited as a major obstacle for the generalization of models. We aimed to develop a
multivariable prognostic model using sociodemographic variables easily obtainable from adolescents at age 15 to predict a depressive disorder diagnosis at age 18 and to evaluate its generalizability in two samples from diverse socioeconomic and cultural settings.
Method: Data from the 1993 Pelotas Birth Cohort were used to develop the prediction model, and its generalizability was evaluated in two representative cohort studies: the Environmental Risk (E-Risk) Longitudinal Twin Study and the Dunedin Multidisciplinary Health and Development
Study.
Results: At age 15, 2,192 adolescents with no evidence of current or previous depression were included (44.6% male). The apparent C-statistic of the models derived in Pelotas ranged from 0.76 to 0.79, and the model obtained from a penalized logistic regression was selected for subsequent external
evaluation. Major discrepancies between the samples were identified, impacting the external prognostic performance of the model (Dunedin and E-Risk C-statistics of 0.63 and 0.59, respectively). The implementation of recommended strategies to account for this heterogeneity among samples improved
the model’s calibration in both samples.
Conclusion: An adolescent depression risk score comprising easily obtainable predictors was developed with good prognostic performance in a Brazilian sample. Heterogeneity among settings was not trivial, but strategies to deal with sample diversity were identified as pivotal for providing better
risk stratification across samples. Future efforts should focus on developing better methodological approaches for incorporating heterogeneity in prognostic research.
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Characterising the ocular surface and tear film in the fifth decade of life: a New Zealand population-based study | 2020
Jennifer P. Craig, Michael T. M. Wang, Antony Ambler, Kirsten Cheyne, Graham A. Wilson
Ocular Surface, 2020, .
https://doi.org/10.1016/j.jtos.2020.08.005
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Our ref: RO739
Purpose: To assess the prevalence of dry eye disease, aqueous tear deficiency, meibomian gland dysfunction, and asymptomatic ocular surface disease in a population-based cohort of 45-year-old New Zealand men and women.
Methods: This cross-sectional study of 885 participants (442 females, 443 males) 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 Developmental Study). Participants were assessed at 45 years of age, and dry eye symptomology, ocular surface characteristics, and tear film quality were evaluated for each participant within a single clinical session. The diagnosis of dry eye disease was made according to the rapid non-invasive dry eye assessment algorithm.
Results: Clinical dry eye signs were present in 402 (45%) participants, of which 78 (9%) participants fulfilled the diagnostic criteria for dry eye disease, and 322 (37%) had asymptomatic ocular surface disease. Among participants with dry eye disease, 22 (2%) exhibited aqueous tear deficiency, and 65 (7%) had meibomian gland dysfunction. Females were more likely to be affected by dry eye disease, meibomian gland dysfunction, and asymptomatic ocular surface disease (all p<0.05).
Conclusions: Clinical dry eye signs were present in almost half of this population-based cohort of 45-year-old New Zealanders, although only 9% of participants fulfilled the diagnostic criteria for dry eye disease. The high prevalence of asymptomatic ocular surface disease presents an opportunity for preventative public health intervention.
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Quantification of the pace of biological aging in humans through a blood test, the DunedinPoAm DNA methylation algorithm | 2020
Daniel W Belsky, Avshalom Caspi, Louise Arseneault, Andrea Baccarelli, David L Corcoran,
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eLife Epidemiology and Global Health, 2020, .
https://doi.org/10.7554/eLife.54870
Our ref: RO738
Biological aging is the gradual, progressive decline in system integrity that occurs with advancing chronological age, causing morbidity and disability. Measurements of the pace of aging are needed as surrogate endpoints in trials of therapies designed to prevent disease by slowing biological aging. We report a blood-DNA-methylation measure that is sensitive to variation in pace of biological aging among individuals born the same year. We first modeled change-over-time in 18 biomarkers tracking organ-system integrity across 12 years of follow-up in n = 954 members of the Dunedin Study born in 1972–1973. Rates of change in each biomarker over ages 26–38 years were composited to form a measure of aging-related decline, termed Pace-of-Aging. Elastic-net regression was used to develop a DNA-methylation predictor of Pace-of-Aging, called DunedinPoAm for Dunedin(P)ace(o)f(A)ging(m)ethylation. Validation analysis in cohort studies and the CALERIE trial provide proof-of-principle for DunedinPoAm as a single-time-point measure of a person’s pace of biological aging.
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Pervasively Thinner Neocortex as a Transdiagnostic Feature of General Psychopathology | 2020
Adrienne L. Romer, Maxwell L. Elliott, Annchen R. Knodt, Maria L. Sison, David Ireland,
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Am J Psychiatry, 2020, .
https://doi.org/10.1176/appi.ajp.2020.19090934
Link to full publication »
Our ref: RO737
Objective:
Neuroimaging research has revealed that structural brain alterations are common across broad diagnostic families of disorders rather than specific to a single psychiatric disorder. Such overlap in the structural brain correlates of mental disorders mirrors already well-documented phenotypic comorbidity of psychiatric symptoms and diagnoses, which can be indexed by a general psychopathology or p factor. The authors hypothesized that if general psychopathology drives the convergence of structural alterations common across disorders, then 1) there should be few associations unique to any one diagnostic family of disorders, and 2) associations with the p factor should overlap with those for the broader diagnostic families.
Methods:
Analyses were conducted on structural MRI and psychopathology data collected from 861 members of the population-representative Dunedin Multidisciplinary Health and Development Study at age 45.
Results:
Study members with high scores across three broad diagnostic families of disorders (externalizing, internalizing, thought disorder) exhibited highly overlapping patterns of reduced global and widely distributed parcel-wise neocortical thickness. Study members with high p factor scores exhibited patterns of reduced global and parcel-wise neocortical thickness nearly identical to those associated with the three broad diagnostic families.
Conclusions:
A pattern of pervasively reduced neocortical thickness appears to be common across all forms of mental disorders and may represent a transdiagnostic feature of general psychopathology. As has been documented with regard to symptoms and diagnoses, the underlying brain structural correlates of mental disorders may not exhibit specificity, and the continued pursuit of such specific correlates may limit progress toward more effective strategies for etiological understanding, prevention, and intervention.
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Occlusal Features and TMJ Clicking: A 30-Year Evaluation from a Cohort Study | 2020
S.J. Olliver, J.M. Broadbent, W.M. Thomson, M. Farella
Journal of Dental Research, 2020, 1-7.
https://doi.org/10.1177/0022034520936235
Our ref: RO736
Occlusal features that deviate from normative values have been historically considered risk factors for temporomandibular joint (TMJ) disorders. Nowadays, a putative association between dental occlusion and TMJ disorders remains controversial, with research findings on associations being inconsistent and inconclusive. We hypothesized that putative occlusal features identified during adolescence are associated with TMJ clicking later in life. The Dunedin Multidisciplinary Health and Development Study is a longitudinal birth cohort study investigation of 1,037 children (48.4% female) born in Dunedin, New Zealand, between April 1, 1972, and March 31, 1973, and assessed repeatedly since then. Associations between posterior crossbite, overbite, and overjet at age 15, as well as both self-reported and clinically assessed TMJ clicking sounds at age 45, were studied. Data were analyzed using multivariate logistic regression, after controlling for sex, emotional style, self-reports of tooth clenching and sleep bruxism, and history of orthodontic treatment. Self-reported and examiner-reported TMJ clicking at age 45 affected 18.3% and 23.8% of the study sample, respectively, and were not associated with the presence of a posterior crossbite or abnormal overjet/overbite values during adolescence. Self-reported history of tooth clenching and emotional style were associated with self-reported TMJ clicking later in life. In addition, there is a suggestion that high overbite during adolescence is negatively associated with TMJ clicking later in life. A history of orthodontic treatment was not associated with TMJ clicking. Abnormal occlusal features, such as posterior crossbite and high and low overjet/overbite in adolescence, are not associated with higher prevalence of TMJ clicking later in life. Personality also appears to influence self-reports of TMJ clicking later in life.
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Association between elevated suPAR, a new biomarker of inflamation, and accelerated aging | 2020
Line Jee Hartmann Rasmussen, Avshalom Caspi, Antony Ambler, Andrea Danese, Maxwell Elliott,
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The Journals of Gerontology: Series A, 2020, .
https://doi.org/10.1093/gerona/glaa178
Link to full publication »
Our ref: RO732
Background
To understand and measure the association between chronic inflammation, aging, and age-related diseases, broadly applicable standard biomarkers of systemic chronic inflammation are needed. We tested whether elevated blood levels of the emerging chronic inflammation marker soluble urokinase plasminogen activator receptor (suPAR) were associated with accelerated aging, lower functional capacity, and cognitive decline.
Methods
We used data from the Dunedin Study, a population-representative 1972–1973 New Zealand birth cohort (n=1037) that has observed participants to age 45 years. Plasma suPAR levels were analyzed at ages 38 and 45 years. We performed regression analyses adjusted for sex, smoking, C-reactive protein, and current health conditions.
Results
Of 997 still-living participants, 875 (88%) had plasma suPAR measured at age 45. Elevated suPAR was associated with accelerated pace of biological aging across multiple organ systems, older facial appearance, and with structural signs of older brain age. Moreover, participants with higher suPAR levels had greater decline in physical function and cognitive function from childhood to adulthood compared to those with lower suPAR levels. Finally, improvements in health habits between ages 38 and 45 (smoking cessation or increased physical activity) were associated with less steep increases in suPAR levels over those years.
Conclusions
Our findings provide initial support for the utility of suPAR in studying the role of chronic inflammation in accelerated aging and functional decline.
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Patterns of recreational cannabis use in Aotearoa New Zealand and their consequences: evidence to inform voters in the 2020 referendum | 2020
Richie Poulton, Kirsten Robertson, Joseph Boden, John Horwood, Reremoana Theodore,
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Journal of the Royal Society of New Zealand, 2020, .
doi.org/10.1080/03036758.2020.1750435
Link to full publication »
Our ref: NZ97
The majority of New Zealanders (approximately 80%) born in the 1970s report using cannabis at least once, despite its illegal status. Four-10% of past-year users were at risk of developing a cannabis dependence syndrome that impaired psychological, social and/or occupational functioning. There were negative psychiatric consequences for a subset of the population who began using cannabis in early/mid-adolescence, particularly in terms of developing psychosis (the risk appeared to be highest for those with a genetic predisposition), and to a lesser degree for depression. There was a consistent dose–response relation between increasing levels of, and/or persistence of cannabis use and a range of deleterious health outcomes including loss of cognitive capacity, increased respiratory symptoms and impaired lung function, periodontal disease, compromised educational achievement and employment history, as well as a host of negative social outcomes (e.g. criminal convictions, relationship difficulties, driving impairment). No discernable impacts upon cardiovascular function were observed. The majority of cannabis users did so with little or no harm. In contrast, a non-trivial minority of the population (approximately 5%–10%) were at heightened risk because they: (i) used cannabis on more days than not; (ii) had become cannabis dependent; or (iii) began using cannabis during mid-adolescence and persisted well into adulthood. Implications are discussed with respect to the 2020 referendum.
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Longitudinal Assessment of Mental Health Disorders and Comorbidities Across 4 Decades Among Participants in the Dunedin Birth Cohort Study | 2020
Caspi, Avshalom, Houts, Renate M., Ambler,
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JAMA Network Open, 2020, 3(4), e203221-e203221.
Link to full publication »
Our ref: RO735
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.To describe mental disorder life histories across the first half of the life course.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.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.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).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.
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Associations between life-course-persistent antisocial behaviour and brain structure in a population-representative longitudinal birth cohort | 2020
Christina O Carlisi, Terrie E Moffitt, Annchen R Knodt, Honalee Harrington, David Ireland,
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Lancet Psychiatry , 2020, 7 245-53.
doi.org/10.1016/S2215-0366(20)30002-X
Link to full publication »
Our ref: RO731
Summary
Background Studies with behavioural and neuropsychological tests have supported the developmental taxonomy theory of antisocial behaviour, which specifies abnormal brain development as a fundamental aspect of life-coursepersistent antisocial behaviour, but no study has characterised features of brain structure associated with lifecourse-persistent versus adolescence-limited trajectories, as defined by prospective data. We aimed to determine whether life-course-persistent antisocial behaviour is associated with neurocognitive abnormalities by testing the hypothesis that it is also associated with brain structure abnormalities.
Methods
We used structural MRI data collected at 45 years of age from participants in the Dunedin Study, a populationrepresentative longitudinal birth cohort of 1037 individuals born between April 1, 1972, and March 31, 1973, in Dunedin, New Zealand, who were resident in the province and who participated in the first assessment at 3 years of age. Participants underwent MRI, and mean global cortical surface area and cortical thickness were extracted for each participant. Participants had been previously subtyped as exhibiting life-course-persistent, adolescence-limited, or no history of persistent antisocial behaviour (ie, a low trajectory group) based on informant-reported and self-reported conduct problems from the ages of 7 years to 26 years. Study personnel who processed the MRI images were masked to antisocial group membership. We used linear estimated ordinary least squares regressions to compare each antisocial trajectory group (life-course persistent and adolescence limited) with the low trajectory group to examine whether antisocial behaviour was related to abnormalities in mean global surface area and mean cortical thickness. Next, we used parcel-wise linear regressions to identify antisocial trajectory group differences in surface area and cortical thickness. All results were controlled for sex and false discovery rate corrected. Findings Data from 672 participants were analysed, and 80 (12%) were classified as having life-course-persistent antisocial behaviour, 151 (23%) as having adolescence-limited antisocial behaviour, and 441 (66%) as having low antisocial behaviour. Individuals on the life-course-persistent trajectory had a smaller mean surface area (standardised β=–0·18 [95% CI –0·24 to –0·11]; p<0·0001) and lower mean cortical thickness (standardised β=–0·10 [95% CI –0·19 to –0·02]; p=0·020) than did those in the low group. Compared with the low group, the life-course-persistent group had reduced surface area in 282 of 360 anatomically defined parcels and thinner cortex in 11 of 360 parcels encompassing circumscribed frontal and temporal regions associated with executive function, affect regulation, and motivation. Widespread differences in brain surface morphometry were not observed for the adolescence-limited group compared with either non-antisocial behaviour or life-course-persistent groups.
Interpretation
These analyses provide initial evidence that differences in brain surface morphometry are associated with life-course-persistent, but not adolescence-limited, antisocial behaviour. As such, the analyses are consistent with the developmental taxonomy theory of antisocial behaviour and highlight the importance of using prospective longitudinal data to define different patterns of antisocial behaviour development.
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Clustering of health, crime and social-welfare inequality in 4 million citizens from two nations | 2020
Leah S. Richmond-Rakerd, Stephanie D’Souza, Signe Hald Andersen, Sean Hogan, Renate M. Houts,
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Nature Human Behaviour, 2020, 4 255-264.
https://doi.org/10.1038/s41562-019-0810-4
Our ref: RO730
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.
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A polygenic score for age-at-first-birth predicts disinhibition | 2020
Leah S. Richmond‐Rakerd, Terrie E. Moffitt, Louise Arseneault, Daniel W. Belsky , Jennie Connor ,
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Journal of Child Psychology and Psychiatry, 2020, .
https://doi.org/10.1111/jcpp.13224
Our ref: RO727
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 withdisinhibitory 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, butrobust across replication. Childhood disinhibition partly mediated associations between the polygenic scoreand 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 provideinsight into the disinhibitory traits and behaviors that accompany early parenthood. Age‐at‐first‐birth is a usefulproxy phenotype for researchers interested in disinhibition. Further, interventions that improve self‐regulationabilities may benefit young parents and their children. Keywords: Reproductive behavior; self‐control; risk‐taking;genetics; longitudinal.
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The Dunedin Multidisciplinary Health and Development Study: oral health findings and their implications | 2020
Chuen Lin Hong, Jonathan M. Broadbent, W. Murray Thomson, Richie Poulton
Journal of the Royal Society of New Zealand, 2020, 50(1), .
https://doi.org/10.1080/03036758.2020.1716816
Our ref: NZ96
Longitudinal research is needed to better understand the natural history of oral conditions and long-term health and social outcomes. Oral health data has been collected periodically in the Dunedin Multidisciplinary Health and Development Study for over 40 years. To date, 70+ peer-review articles on the Study’s oral health-related findings have been published, providing insight into the natural history of oral conditions, risk factors, impacts on quality of life, and disparities in oral health. Some of these report new findings, while others build upon the existing body of evidence. This paper provides an overview of these findings and reflects on their public health implications and policy utility in New Zealand.
« Hide abstract
A risk calculator to predict adult attention-deficit/hyperactivity disorder: generation and external validation in three birth cohorts and one clinical sample | 2019
Caye, Arthur; Jessica Agnew-Blais; Louise Arseneault; Ives Cavalcante-Passos; Helen Gonçalves; Christian Kieling; Kate Langley; Ana M. B. Menezes; Terrie E Moffitt; Anita Thapar; Thiago Botter-Maio Rocha; Margaret Sibley; James M. Swanson; Fernando Wehrmeister; Luis Augusto Rohde.
Epidemiology and Psychiatric Sciences, 2019, 29(37), .
https://doi.org/10.1017/s2045796019000283
Link to full publication »
Our ref: RO756
Aim: Few personalised medicine investigations have been conducted for mental health. We aimed to generate and validate a risk tool that predicts adult attention-deficit/hyperactivity disorder (ADHD).
Methods: Using logistic regression models, we generated a risk tool in a representative population cohort (ALSPAC - UK, 5113 participants, followed from birth to age 17) using childhood clinical and sociodemographic data with internal validation. Predictors included sex, socioeconomic status, single-parent family, ADHD symptoms, comorbid disruptive disorders, childhood maltreatment, ADHD symptoms, depressive symptoms, mother's depression and intelligence quotient. The outcome was defined as a categorical diagnosis of ADHD in young adulthood without requiring age at onset criteria. We also tested Machine Learning approaches for developing the risk models: Random Forest, Stochastic Gradient Boosting and Artificial Neural Network. The risk tool was externally validated in the E-Risk cohort (UK, 2040 participants, birth to age 18), the 1993 Pelotas Birth Cohort (Brazil, 3911 participants, birth to age 18) and the MTA clinical sample (USA, 476 children with ADHD and 241 controls followed for 16 years from a minimum of 8 and a maximum of 26 years old).
Results: The overall prevalence of adult ADHD ranged from 8.1 to 12% in the population-based samples, and was 28.6% in the clinical sample. The internal performance of the model in the generating sample was good, with an area under the curve (AUC) for predicting adult ADHD of 0.82 (95% confidence interval (CI) 0.79-0.83). Calibration plots showed good agreement between predicted and observed event frequencies from 0 to 60% probability. In the UK birth cohort test sample, the AUC was 0.75 (95% CI 0.71-0.78). In the Brazilian birth cohort test sample, the AUC was significantly lower -0.57 (95% CI 0.54-0.60). In the clinical trial test sample, the AUC was 0.76 (95% CI 0.73-0.80). The risk model did not predict adult anxiety or major depressive disorder. Machine Learning approaches did not outperform logistic regression models. An open-source and free risk calculator was generated for clinical use and is available online at https://ufrgs.br/prodah/adhd-calculator/.
Conclusions: The risk tool based on childhood characteristics specifically predicts adult ADHD in European and North-American population-based and clinical samples with comparable discrimination to commonly used clinical tools in internal medicine and higher than most previous attempts for mental and neurological disorders. However, its use in middle-income settings requires caution.
« Hide abstract
Psychiatry’s Opportunity to Prevent the Rising Burden of Age-Related Disease | 2019
Terrie E. Moffitt, Avshalom Caspi
JAMA Psychiatry, 2019, 76(5), 461–462.
https://doi.org/10.1001/jamapsychiatry.2019.0037
Link to full publication »
Our ref: RO755
Three demographic trends are colliding to form a perfect storm: the postretirement portion of the population is swelling, the human life span is lengthening, and the birth rate is dropping. The result is that the balance of young to old in the population is shifting, leaving fewer young workers to drive the economy and pay taxes to support aging citizens. These 3 trends mean more stress for the young and less support for the old, bringing 2 opportunities for the mental health field. First, an opportunity to prevent disability among young people, which would enhance their well-being and capacity to shoulder the burden of the dependent older population. Young people tend to be physically healthy but can experience behavioral problems, emotional problems, substance abuse, and cognitive impairments. These conditions respond to mental health treatments. Second, an opportunity to prevent ill health among older people, which would reduce the burden of age-related disability. Here, we argue that psychiatry is well situated to prevent disability among older people by doing something it does well: treat young people. Risk-prediction research shows that the same people who have poor mental and cognitive health while young tend to have age-related diseases years later.1,2 Moreover, the timing is right. Mental disorders peak in adolescence and young adulthood, whereas noninfectious diseases peak in midlife and neurodegenerative conditions peak in late life.
« Hide abstract
Brain-age in midlife is associated with accelerated biological aging and cognitive decline in a longitudinal birth cohort | 2019
Elliott, M.L. Belsky, D.W., Knodt, A.R.,
... Show all »
Molecular Psychiatry, 2019, .
https://doi.org/10.1038/s41380-019-0626-7
Our ref: RO733
An individual’s brainAGE is the difference between chronological age and age predicted from machine-learning models of brain-imaging data. BrainAGE has been proposed as a biomarker of age-related deterioration of the brain. Having an older brainAGE has been linked to Alzheimer’s, dementia, and mortality. However, these findings are largely based on crosssectional associations which can confuse age differences with cohort differences. To illuminate the validity of brainAGE as a biomarker of accelerated brain aging, a study is needed of a large cohort all born in the same year who nevertheless vary on brainAGE. In the Dunedin Study, a population-representative 1972–73 birth cohort, we measured brainAGE at age 45 years, as well as the pace of biological aging and cognitive decline in longitudinal data from childhood to midlife (N = 869). In this cohort, all chronological age 45 years, brainAGE was measured reliably (ICC = 0.81) and ranged from 24 to 72 years. Those with older midlife brainAGEs tended to have poorer cognitive function in both adulthood and childhood, as well as impaired brain health at age 3. Furthermore, those with older brainAGEs had an accelerated pace of biological aging, older facial appearance, and early signs of cognitive decline from childhood to midlife. These findings help to validate brainAGE as a potential surrogate biomarker for midlife intervention studies that seek to measure dementia-prevention efforts in midlife. However, the findings also caution against the assumption that brainAGE scores represent only age-related deterioration of the brain as they may also index central nervous system variation present since childhood.
« Hide abstract
White matter hyperintensities are common in midlife and already associated with cognitive decline | 2019
Tracy d’Arbeloff, Maxwell L. Elliott, Annchen R. Knodt, Tracy R. Melzer, Ross Keenan,
... Show all »
Brain Communications, 2019, 1(1), .
https://doi.org/10.1093/braincomms/fcz041
Our ref: RO728
White matter hyperintensities proliferate as the brain ages and are associated with increased risk for cognitive decline as well as Alzheimer’s disease and related dementias. As such, white matter hyperintensities have been targeted as a surrogate biomarker in intervention trials with older adults. However, it is unclear at what stage of aging white matter hyperintensities begin to relate to cognition and if they may be a viable target for early prevention. In the Dunedin Study, a population-representative cohort followed since birth, we measured white matter hyperintensities in 843 45-year-old participants using T2-weighted magnetic resonance imaging and we assessed cognitive decline from childhood to midlife. We found that white matter hyperintensities were common at age 45 and that white matter hyperintensity volume was modestly associated with both lower childhood (ß = −0.08, P = 0.013) and adult IQ (ß=−0.15, P < 0.001). Moreover, white matter hyperintensity volume was associated with greater cognitive decline from childhood to midlife (ß=−0.09, P < 0.001). Our results demonstrate that a link between white matter hyperintensities and early signs of cognitive decline is detectable decades before clinical symptoms of dementia emerge. Thus, white matter hyperintensities may be a useful surrogate biomarker for identifying individuals in midlife at risk for future accelerated cognitive decline and selecting participants for dementia prevention trials.
« Hide abstract
Replicability of structural brain alterations associated with general psychopathology: evidence from a population-representative birth cohort | 2019
Romer, A. L., Knodt, A. R., Sison,
... Show all »
Molecular Psychiatry, 2019, .
https://doi.org/10.1038/s41380-019-0621-z
Our ref: RO726
Transdiagnostic research has identified a general psychopathology factor – often called the ‘p’
factor – that accounts for shared liability to internalizing, externalizing, and thought disorders in
diverse samples. It has been argued that the p factor may reflect dysfunctional thinking present
in serious mental illness. In support of this, we previously used a theory-free, data-driven
multimodal neuroimaging approach to find that higher p factor scores are associated with
structural deficits within a cerebello-thalamo-cortical circuit (CTCC) and visual association
cortex, both of which are important for monitoring and coordinating information processing in
the service of executive control. Here we attempt to replicate these associations by conducting
region-of-interest analyses of the CTCC and visual association cortex using data from 831
members of the Dunedin Multidisciplinary Health and Development Study, a five-decade
longitudinal study of a population-representative birth cohort now 45 years old. We further
sought to replicate a more recent report that p factor scores can be predicted by patterns of
distributed cerebellar morphology as estimated through independent component analysis. We
successfully replicated associations between higher p factor scores and both reduced grey
matter volume of the visual association cortex and fractional anisotropy of pontine white
matter pathways within the CTCC. In contrast, we failed to replicate prior associations between
cerebellar structure and p factor scores. Collectively, our findings encourage further focus on
the CTCC and visual association cortex as core neural substrates and potential biomarkers of
transdiagnostic risk for mental illness.
« Hide abstract
Epigenome-wide Association Study of Attention-Deficit/Hyperactivity Disorder Symptoms in Adults | 2019
Jenny van Dongen, Nuno R. Zilhão, Karen Sugden, BIOS Consortium, Eilis J. Hannon,
... Show all »
Biological Psychiatry, 2019, 86(8), 559-607.
https://doi.org/10.1016/j.biopsych.2019.02.016
Link to full publication »
Our ref: RO720
Background
Previous studies have reported associations between attention-deficit/hyperactivity disorder symptoms and DNA methylation in children. We report the first epigenome-wide association study meta-analysis of adult attention-deficit/hyperactivity disorder symptoms, based on peripheral blood DNA methylation (Infinium HumanMethylation450K array) in three population-based adult cohorts.
Methods
An epigenome-wide association study was performed in the Netherlands Twin Register (N = 2258, mean age 37 years), Dunedin Multidisciplinary Health and Development Study (N = 800, age 38 years), and Environmental Risk Longitudinal Twin Study (N = 1631, age 18 years), and results were combined through meta-analysis (total sample size N = 4689). Region-based analyses accounting for the correlation between nearby methylation sites were also performed.
Results
One epigenome-wide significant differentially methylated position was detected in the Dunedin study, but meta-analysis did not detect differentially methylated positions that were robustly associated across cohorts. In region-based analyses, six significant differentially methylation regions (DMRs) were identified in the Netherlands Twin Register, 19 in the Dunedin study, and none in the Environmental Risk Longitudinal Twin Study. Of these DMRs, 92% were associated with methylation quantitative trait loci, and 68% showed moderate to large blood-brain correlations for DNA methylation levels. DMRs included six nonoverlapping DMRs (three in the Netherlands Twin Register, three in the Dunedin study) in the major histocompatibility complex, which were associated with expression of genes in the major histocompatibility complex, including C4A and C4B, previously implicated in schizophrenia.
« Hide abstract
Genetics of nurture: A test of the hypothesis that parents' genetics predict their observed caregiving | 2019
Wertz J Belsky J Moffitt TE Belsky DW., Harrington H., Avinun R., Poulton R., Ramrakha S.,
... Show all »
Development Psychology, 2019, 55(7), 1461–1472.
Link to full publication »
Our ref: RO716
Twin studies have documented that parenting behavior is partly heritable, but it is unclear how parents' genetics shape their caregiving. Using tools of molecular genetics, the present study investigated this process by testing hypotheses about associations between a genome-wide polygenic score for educational attainment and parental caregiving in 702 members of the Dunedin Study, a population-representative birth cohort. Data have been prospectively collected from when Study members were born through to midlife, and include assessments of the caregiving they provided once they became parents. Results showed that parents' polygenic scores predicted warm, sensitive, and stimulating caregiving, both in personal interactions with their young children (as captured on video) and through the home environments they created for their families (as observed by home visitors). The magnitude of this effect was small. Polygenic-score associations were independent of well-established predictors of parenting, such as parents' own childhood experiences of parenting and the age at which they became parents. Polygenic-score associations were mediated by parents' early-emerging cognitive abilities and self-control skills. Findings have implications for theory and research about genetic influences on caregiving and child development. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
« Hide abstract
Association of Neurocognitive and Physical Function With Gait Speed in Midlife | 2019
Line Jee Hartmann Rasmussen, Avshalom Caspi, Antony Ambler, Jonathan M. Broadbent, Harvey J. Cohen,
... Show all »
JAMA Network Open, 2019, .
10.1001/jamanetworkopen.2019.13123
Link to full publication »
Our ref: RO725
IMPORTANCE Gait speed is a well-known indicator of risk of functional decline and mortality in older adults, but little is known about the factors associated with gait speed earlier in life.
OBJECTIVES To test the hypothesis that slow gait speed reflects accelerated biological aging at midlife, as well as poor neurocognitive functioning in childhood and cognitive decline from childhood to midlife.
DESIGN, SETTING, AND PARTICIPANTS This cohort study uses data from the Dunedin Multidisciplinary Health and Development Study, a population-based study of a representative 1972
to 1973 birth cohort in New Zealand that observed participants to age 45 years (until April 2019). Data analysis was performed from April to June 2019.
EXPOSURES Childhood neurocognitive functions and accelerated aging, brain structure, and concurrent physical and cognitive functions in adulthood.
MAIN OUTCOMES AND MEASURES Gait speed at age 45 years, measured under 3 walking conditions: usual, dual task, and maximum gait speeds.
RESULTS Of the 1037 original participants (91% of eligible births; 535 [51.6%] male), 997 were alive at age 45 years, of whom 904 (90.7%) had gait speed measured (455 [50.3%] male; 93%white). The mean (SD) gait speeds were 1.30 (0.17) m/s for usual gait, 1.16 (0.23) m/s for dual task gait, and 1.99 (0.29) m/s for maximum gait. Adults with more physical limitations (standardized regression coefficient [β], −0.27; 95%CI, −0.34 to −0.21; P < .001), poorer physical functions (ie, weak grip strength [β, 0.36; 95%CI, 0.25 to 0.46], poor balance [β, 0.28; 95%CI, 0.21 to 0.34], poor visualmotor coordination [β, 0.24; 95%CI, 0.17 to 0.30], and poor performance on the chair-stand [β, 0.34; 95%CI, 0.27 to 0.40] or 2-minute step tests [β, 0.33; 95%CI, 0.27 to 0.39]; all P < .001), accelerated biological aging across multiple organ systems (β, −0.33; 95%CI, −0.40 to −0.27; P < .001), older facial appearance (β, −0.25; 95%CI, −0.31 to −0.18; P < .001), smaller brain volume (β, 0.15; 95%CI, 0.06 to 0.23; P < .001), more cortical thinning (β, 0.09; 95%CI, 0.02 to 0.16; P = .01), smaller cortical surface area (β, 0.13; 95%CI, 0.04 to 0.21; P = .003), and more white matter hyperintensities (β, −0.09; 95%CI, −0.15 to −0.02; P = .01) had slower gait speed. Participants with lower IQ in midlife (β, 0.38; 95%CI, 0.32 to 0.44; P < .001) and participants who exhibited cognitive
decline from childhood to adulthood (β, 0.10; 95%CI, 0.04 to 0.17; P < .001) had slower gait at age 45 years. Those with poor neurocognitive functioning as early as age 3 years had slower gait in midlife (β, 0.26; 95%CI, 0.20 to 0.32; P < .001).
« Hide abstract
Childhood and adolescent television viewing and internalising disorders in adulthood | 2019
Helena M McAnally, Tamara Young, Robert J Hancox
Preventive Medicine Reports, 2019, 15 100890.
https://doi.org/10.1016/j.pmedr.2019.100890
Our ref: RO722
Time spent watching television during childhood and adolescence has been linked to socio-emotional and physical health problems in adulthood. It is unclear whether excessive television viewing is a risk factor for internalising mental health disorders such as anxiety and depression. Longitudinal associations between television viewing in childhood and adult diagnoses of anxiety and depression were investigated in a population-based birth cohort from Dunedin, New Zealand. Mean weekday television viewing time was reported by parents and adolescents between ages 5 and 15 years (1977-1987). Diagnoses of any anxiety disorder and major depression were made using standard criteria from symptoms reported for the previous year at ages 18, 21, 26, 32, and 38 years (between 1990 and 2012). Analyses adjusted for sex, parent and teacher reports of worry/fearfulness at age 5, and socioeconomic status during childhood. Diagnoses were counted if present at any of these assessments. Approximately half of all participants met criteria for anxiety disorder or depression during at least one adult assessment. Participants who had watched more television during childhood and adolescence were more likely to have a diagnosis of anxiety in sex-adjusted analyses (OR [95% CI] 1.22 [1.05, 1.41], p=0.01), although this association weakened after adjustment for early childhood worry/fearfulness and socioeconomic status. There was no association between television viewing and depression in sex- or fully-adjusted analyses. Excessive television viewing during childhood and adolescence may be a risk factor for developing an anxiety disorder in adulthood, but does not appear to influence the long-term risk for major depression.
« Hide abstract
Associations between lung and endothelial function in early middle age | 2019
Robert J. Hancox, Lathan Thomas, Michael J.A. Williams, Malcolm R. Sears
Respirology, 2019, .
https://doi.org/10.1111/resp.13556
Our ref: RO723
Background and objective
Chronic lung disease is associated with impaired endothelial function and this may be a risk factor for poor cardiovascular health. It is unknown if there is an association between lung and endothelial function in the general population. We investigated associations between lung and endothelial function in a population‐based cohort of 38‐year‐old men and women.
Methods
Systemic endothelial function was measured using peripheral arterial tonometry to calculate the Framingham reactive hyperaemia index. Lung function was assessed using spirometry, plethysmographic lung volumes, airway conductance and gas transfer. Associations between lung and endothelial function were assessed with and without adjustment for potential confounding factors using regression analyses.
Results
Sex modified the association between lung and endothelial function. Among women, lower values of pre‐ and post‐bronchodilator spirometry, total lung capacity and functional residual capacity (FRC) were associated with worse endothelial function (P < 0.05). These associations persisted after adjustment for smoking, asthma diagnoses, fitness and body mass index. Associations were weaker among men: only FRC, airway conductance and post‐bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratios were associated with endothelial function. Endothelial function was not associated with gas transfer in either sex.
Conclusion
Lower lung volumes and airflow obstruction are associated with endothelial dysfunction among women. There is weaker evidence for an association between airway and endothelial function in men. These findings may partly explain the increased risk of cardiovascular disease among people with poor lung function, but suggest that there are sex differences in this association.
« Hide abstract
Smoking does not accelerate leucocyte telomere attrition: a meta-analysis of 18 longitudinal cohorts | 2019
Melissa Bateson, Abraham Aviv, Laila Bendix, Athanase Benetos, Yoav Ben-Shlomo,
... Show all »
The Royal Society Open Science, 2019, 6(6), .
https://doi.org/10.1098/rsos.190420
Our ref: RO721
Smoking is associated with shorter leucocyte telomere length (LTL), a biomarker of increased morbidity and reduced longevity. This association is widely interpreted as evidence that smoking causes accelerated LTL attrition in adulthood, but the evidence for this is inconsistent. We analysed the association between smoking and LTL dynamics in 18 longitudinal cohorts. The dataset included data from 12 579 adults (4678 current smokers and 7901 non-smokers) over a mean follow-up interval of 8.6 years. Meta-analysis confirmed a cross-sectional difference in LTL between smokers and non-smokers, with mean LTL 84.61 bp shorter in smokers (95% CI: 22.62 to 146.61). However, LTL attrition was only 0.51 bp yr−1 faster in smokers than in non-smokers (95% CI: −2.09 to 1.08), a difference that equates to only 1.32% of the estimated age-related loss of 38.33 bp yr−1. Assuming a linear effect of smoking, 167 years of smoking would be required to generate the observed cross-sectional difference in LTL. Therefore, the difference in LTL between smokers and non-smokers is extremely unlikely to be explained by a linear, causal effect of smoking. Selective adoption, whereby individuals with short telomeres are more likely to start smoking, needs to be considered as a more plausible explanation for the observed pattern of telomere dynamics.
« Hide abstract
General functional connectivity: Shared features of resting-state and task fMRI drive reliable and heritable individual differences in functional brain networks | 2019
Maxwell L. Elliott, Annchen R. Knodt, Megan Cooke, M. Justin Kim, Tracy R. Melzer,
... Show all »
NeuroImage, 2019, 189 516-532.
https://doi.org/10.1016/j.neuroimage.2019.01.068
Link to full publication »
Our ref: RO719
Intrinsic connectivity, measured using resting-state fMRI, has emerged as a fundamental tool in the study of the human brain. However, due to practical limitations,
many studies do not collect enough resting-state data to generate reliable measures of intrinsic connectivity necessary for studying individual differences. Here we
present general functional connectivity (GFC) as a method for leveraging shared features across resting-state and task fMRI and demonstrate in the Human Connectome
Project and the Dunedin Study that GFC offers better test-retest reliability than intrinsic connectivity estimated from the same amount of resting-state data
alone. Furthermore, at equivalent scan lengths, GFC displayed higher estimates of heritability than resting-state functional connectivity. We also found that predictions
of cognitive ability from GFC generalized across datasets, performing as well or better than resting-state or task data alone. Collectively, our work suggests that GFC can improve the reliability of intrinsic connectivity estimates in existing datasets and, subsequently, the opportunity to identify meaningful correlates of individual differences in behavior. Given that task and resting-state data are often collected together, many researchers can immediately derive more reliable measures of intrinsic connectivity through the adoption of GFC rather than solely using resting-state data. Moreover, by better capturing heritable variation in intrinsic connectivity, GFC represents a novel endophenotype with broad applications in clinical neuroscience and biomarker discovery.
« Hide abstract
A Polygenic Score for Higher Educational Attainment is Associated with Larger Brains | 2019
Elliott, M. L. Belsky, D. W. Anderson, K. Corcoran, D. L. Ge,
... Show all »
Cerebal Cortex, 2019, 1-9.
https://doi.org/10.1093/cercor/bhy219
Our ref: RO706
People who score higher on intelligence tests tend to have larger brains. Twin studies suggest the same genetic factors influence both brain size and intelligence. This has led to the hypothesis that genetics influence intelligence partly by contributing to development of larger brains. We tested this hypothesis with molecular genetic data using discoveries from a genome-wide association study (GWAS) of educational attainment, a correlate of intelligence. We analyzed genetic, brain imaging, and cognitive test data from the UK Biobank, the Dunedin Study, the Brain Genomics Superstruct Project (GSP), and the Duke Neurogenetics Study (DNS) (combined N=8,271). We measured genetics using polygenic scores based on published GWAS. We conducted meta-analysis to test associations among participants' genetics, total brain volume (i.e., brain size), and cognitive test performance. Consistent with previous findings, participants with higher polygenic scores achieved higher scores on cognitive tests, as did participants with larger brains. Participants with higher polygenic scores also had larger brains. We found some evidence that brain size partly mediated associations between participants' education polygenic scores and their cognitive test performance. Effect-sizes were larger in the population-based UK Biobank and Dunedin samples than in the GSP and DNS samples. Sensitivity analysis suggested this effect-size difference partly reflected restricted range of cognitive performance in the GSP and DNS samples. Recruitment and retention of population-representative samples should be a priority for neuroscience research. Findings suggest promise for studies integrating GWAS discoveries with brain imaging data to understand neurobiology linking genetics with individual differences in cognitive performance.
« Hide abstract
Childhood IQ predicts age-38 oral disease experience and service-use | 2019
Thomson WM, Broadbent JM, Caspi A, Poulton R, Moffitt TE
Community Dentistry and Oral Epidemiology, 2019, 47(3), 252-258.
https://doi.org/10.1111/cdoe.12451
Our ref: RO718
OBJECTIVES:
Given that people with higher intelligence have been shown to live longer, enjoy better health and have more favourable health behaviours, we investigated the association between childhood IQ and a range of important dental health and service-use indicators at age 38.
METHODS:
Long-standing prospective study of a complete birth cohort, with childhood IQ (assessed at ages 7, 9, 11 and 13 years) used to allocate participants (N = 818) to one of four ordinal categories of childhood IQ.
RESULTS:
There were distinct and consistent gradients by childhood IQ in almost all of the dental caries experience measures (with the exception of filled teeth) whereby each was most severe in the lowest child IQ category and least severe in the highest; the exception was the mean FT score, for which there was no discernible gradient. Indicators of self-care and periodontal disease experience showed similar gradients, and multivariate modelling using the continuous IQ score confirmed the observed patterns.
CONCLUSIONS:
Childhood cognitive function is a key determinant of oral health and dental service-use by midlife, with those of lower cognitive capacity as children likely to have poorer oral health, less favourable oral health-related beliefs, and more detrimental self-care and dental visiting practices by age 38. There is a need to shape dental clinical services and public health interventions so that people with the poorest cognitive function do not continue to be disadvantaged.
« Hide abstract
Establishing a generalized polyepigenetic biomarker for tobacco smoking | 2019
Sugden K, Hannon E J, Arseneault L, Belsky DW, Broadbent JM,
... Show all »
Translational Psychiatry, 2019, 9 .
https://doi.org/10.1038/s41398-019-0430-9
Our ref: RO717
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
« Hide abstract
Effect modification of FADS2 polymorphisms on the association between breastfeeding and intelligence: results from a collaborative meta-analysis | 2019
Hartwig FP, Davies NM, Horta BL, Ahluwalia TS, Bisgaard H,
... Show all »
International Journal of Epidemiology, 2019, 48(1), 45–57.
https://doi.org/10.1093/ije/dyy273
Our ref: RO715
BACKGROUND:
Accumulating evidence suggests that breastfeeding benefits children's intelligence, possibly due to long-chain polyunsaturated fatty acids (LC-PUFAs) present in breast milk. Under a nutritional adequacy hypothesis, an interaction between breastfeeding and genetic variants associated with endogenous LC-PUFAs synthesis might be expected. However, the literature on this topic is controversial.
METHODS:
We investigated this gene × environment interaction through a collaborative effort. The primary analysis involved >12 000 individuals and used ever breastfeeding, FADS2 polymorphisms rs174575 and rs1535 coded assuming a recessive effect of the G allele, and intelligence quotient (IQ) in Z scores.
RESULTS:
There was no strong evidence of interaction, with pooled covariate-adjusted interaction coefficients (i.e. difference between genetic groups of the difference in IQ Z scores comparing ever with never breastfed individuals) of 0.12[(95% confidence interval (CI): -0.19; 0.43] and 0.06 (95% CI: -0.16; 0.27) for the rs174575 and rs1535 variants, respectively. Secondary analyses corroborated these results. In studies with ≥5.85 and <5.85 months of breastfeeding duration, pooled estimates for the rs174575 variant were 0.50 (95% CI: -0.06; 1.06) and 0.14 (95% CI: -0.10; 0.38), respectively, and 0.27 (95% CI: -0.28; 0.82) and -0.01 (95% CI: -0.19; 0.16) for the rs1535 variant.
CONCLUSIONS:
Our findings did not support an interaction between ever breastfeeding and FADS2 polymorphisms. However, subgroup analysis suggested that breastfeeding may supply LC-PUFAs requirements for cognitive development if breastfeeding lasts for some (currently unknown) time. Future studies in large individual-level datasets would allow properly powered subgroup analyses and further improve our understanding on the breastfeeding × FADS2 interaction.
« Hide abstract
Association of Childhood Lead Exposure With Adult Personality Traits and Lifelong Mental Health | 2019
Reuben, Aaron Schaefer, Jonathan Moffitt, Terrie Broadbent, Jonathan Harrington,
... Show all »
JAMA Psychiatry, 2019, 76(4), 418-425.
10.1001/jamapsychiatry.2018.4192
Our ref: RO714
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
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Cumulative childhood risk is associated with a new measure of chronic inflammation in adulthood | 2019
Rasmussen, L.J.H., Moffitt, T.E., Eugen-Olsen,
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Journal of Child Psychology and Psychiatry, 2019, 60(2), 199-208.
10.1111/jcpp.12928
Link to full publication »
Our ref: RO708
Background:Childhood risk factors are associated with elevated inflammatory biomarkers in adulthood, but it isunknown whether these risk factors are associated with increased adult levels of the chronic inflammation markersoluble urokinase plasminogen activator receptor (suPAR). We aimed to test the hypothesis that childhood exposureto 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-representa-tive 1972–1973 birth cohort; the Dunedin Multidisciplinary Health and Development Study observed participants toage 38 years. Main childhood predictors were poor health, socioeconomic disadvantage, adverse childhoodexperiences (ACEs), low IQ, and poor self-control. Main adult outcomes were adulthood inflammation measuredas suPAR and high-sensitivity CRP (hsCRP).Results:Participants with available plasma samples at age 38 wereincluded (N=837, 50.5% male). suPAR (mean 2.40 ng/ml;SD0.91) was positively correlated with hsCRP (r0.15,p<.001). After controlling for sex, body mass index (BMI), and smoking, children who experienced more ACEs, lowerIQ, or had poorer self-control showed elevated adult suPAR. When the five childhood risks were aggregated into aCumulative Childhood Risk index, and controlling for sex, BMI, and smoking, Cumulative Childhood Risk wasassociated with higher suPAR (b0.10; SE 0.03;p=.002). Cumulative Childhood Risk predicted elevated suPAR, aftercontrolling for hsCRP (b0.18; SE 0.03;p<.001).Conclusions:Exposure to more childhood risk factors wasassociated with higher suPAR levels, independent of CRP. suPAR is a useful addition to studies connecting childhoodrisk to adult inflammatory burden.
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Does physical fitness enhance lung function in children and young adults? | 2018
Robert J. Hancox, Finn Rasmussen
European Respiratory Journal, 2018, 51(2), .
https://doi.org/10.1183/13993003.01374-2017
Our ref: RO713
Although physical activity is important for lung health, it is unclear whether physical fitness influences lung function. We investigated associations between lung function and fitness in two population-based cohort studies of children and young adults.
Aerobic fitness was measured using a maximal cycle ergometer test at ages 9, 15, 21 and 29 years in Odense, Denmark and using a submaximal cycle test at ages 15, 26, 32 and 38 years in Dunedin, New Zealand.
Aerobic fitness was positively associated with forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) in cross-sectional analyses at all ages in both cohorts, independently of height, weight, sex, asthma and smoking. Each standard deviation difference in fitness was associated with 2–3% predicted higher values of FEV1 and FVC. Improvements in fitness during childhood and adolescence were associated with growth in lung volumes in longitudinal analyses. These associations tended to be stronger in males than females. No longitudinal associations were found after peak adult lung function had been attained. Fitness was not significantly associated with FEV1/FVC ratios.
Aerobic fitness is positively associated with lung volumes. Improving fitness during childhood and adolescence is associated with greater adult lung volumes, but not with airway calibre.
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Intergenerational changes in adolescents’ physical fitness and weight in New Zealand | 2018
McAnally HM, Reeves LM, Sligo JL, Hancox RJ
The New Zealand medical journal, 2018, 131(1482), 16-28.
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Our ref: NZ95
AIMS:
This research examines fitness and body weight in two cohorts of adolescents, to determine continuity and changes in these measures across two generations.
METHODS:
Height, weight and fitness were measured in a population-based cohort of 15 year-olds in 1986/7 (Dunedin Study, n=968). The same measures were obtained for their 15-16 year-old children between 2007 and 2015 (Next Generation Study, n=343). Fitness was defined as maximal aerobic capacity (V'O2max). Height and weight were measured in all participants and fitness was adjusted for weight (V'O2max/kg).
RESULTS:
The Next Generation participants were, on average, heavier than the Dunedin Study participants had been, and had higher body mass index values (kg/m2). Unadjusted V'O2max values for boys did not differ between generations, but were lower in Next Generation girls compared to Dunedin Study girls. For both sexes, the Next Generation participants had lower weight-adjusted V'O2max values than the Dunedin Study participants. Compared to their parents, weight-adjusted V'O2max values were approximately 25% lower in girls and 15% lower in boys.
CONCLUSIONS:
Overall adolescents today appear to be less fit and heavier than their parents were at the same age. The decline in fitness over a generation is particularly evident in adolescent girls, although boys also have lower levels of fitness once body weight has been taken into account.
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Periodontitis and multiple markers of cardiometabolic risk in the fourth decade: A cohort study | 2018
Shearer, D. M. Thomson, W. M. Cameron, C. M. Ramrakha, S. Wilson,
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Community Dentistry and Oral Epidemiology, 2018, 46(6), 615-623.
Link to full publication »
Our ref: RO712
OBJECTIVES: To examine associations between periodontitis at ages 32 and 38 and a range of early cardiometabolic risk biomarkers at age 38. METHODS: Periodontal probing depth and bleeding on probing data collected during the age-32 and age-38 assessments in the Dunedin Multidisciplinary Health and Development Study were used to quantify periodontal inflammatory load. Retinal microvascular abnormalities, endothelial dysfunction, and metabolic syndrome data were collected during the age-38 assessment. Regression models were used to examine associations between these cardiometabolic risk markers and (1) the inflammatory load at age 38 and (2) the change in inflammatory load between ages 32 and 38. RESULTS: Periodontal inflammatory load was recorded for 890 Study members at age 32, 891 at age 38, and 856 at both ages. Retinal vessel data were available for 922, endothelial dysfunction data for 909 and metabolic syndrome data for 905 at age 38. Neither the inflammatory load of periodontitis at 38 nor the changes in inflammatory load 32-38 were found to be associated with any of the three cardiometabolic risk markers. CONCLUSIONS: Periodontitis was not associated with markers of cardiometabolic risk at this relatively early stage in the life course. It is possible that any influence of periodontitis on cardiometabolic health develops later in life, or periodontitis is not involved in the putative causal chain comprising systemic inflammation, cardiometabolic risk markers, and subsequent cardiovascular risk.
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Genetic analysis of social mobility in five longitudinal studies | 2018
Belsky, D.W. Domingue, B.W Wedow, R Arseneault, L. Boardman,
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PNAS (Proceedings of the National Academy of Sciences of the USA), 2018, 115(13), E7275-E7284.
https://www.pnas.org/doi/full/10.1073/pnas.1801238115
Our ref: RO702
A summary genetic measure, called a “polygenic score,” derived from a genome-wide association study (GWAS) of education can modestly predict a person’s educational and economic success. This prediction could signal a biological mechanism: Educationlinked genetics could encode characteristics that help people get ahead in life. Alternatively, prediction could reflect social history: People from well-off families might stay well-off for social reasons, and these families might also look alike genetically. A key test to distinguish biological mechanism from social history is if people with higher education polygenic scores tend to climb the social ladder beyond their parents’ position. Upward mobility would indicate education-linked genetics encodes characteristics that foster success. We tested if education-linked polygenic scores predicted social mobility in >20,000 individuals in five longitudinal studies in the United States, Britain, and New Zealand. Participants with higher polygenic scores achieved more education and career success and accumulated more wealth. However, they also tended to come from better-off families. In the key test, participants with higher polygenic scores tended to be upwardly mobile compared with their parents. Moreover, in sibling-difference analysis, the sibling with the higher polygenic score was more upwardly mobile. Thus, education GWAS discoveries are not mere correlates of privilege; they influence social mobility within a life. Additional analyses revealed that a mother’s polygenic score predicted her child’s attainment over and above the child’s own polygenic score, suggesting parents’ genetics can also affect their children’s attainment through environmental pathways. Education GWAS discoveries affect socioeconomic attainment through influence on individuals’ family-oforigin environments and their social mobility.
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