Publications
All peer reviewed publications are listed below.
Displaying page 2 of 23.
Changes in incisor relationship over the life course - Findings from a cohort study | 2022
Olliver SJ., Broadbent JM., Prasad, S., Cai,
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Journal of Dentistry, 2022, 117 .
https://doi.org/10.1016/j.jdent.2021.103919
Link to full publication »
Our ref: RO771
OBJECTIVE: The aim of this longitudinal cohort study was to investigate the changes in incisor relationship over three decades from adolescence to mid-adulthood. MATERIALS AND METHODS: The sample included 1,037 children (48.4% female) born between April 1972 and March 1973 from the longitudinal birth cohort Dunedin Multidisciplinary Health and Development Study. Overjet and overbite values were assessed at age 15 and 45 years and entered in a regression model as outcome variables. Baseline occlusal variables, sex, history of orthodontic treatment, periodontal data recorded at age 38, and self-reported oral parafunction and orthodontic treatment history recorded at age 45 were entered as covariates in the regression analysis. RESULTS: Regression modelling showed that overjet/overbite category (high or low) at age 15 tends to predict overjet/overbite category at age 45, with overjet become slightly larger (around +0.5mm) and overbite slightly lower (-0.5mm) over time. Study members with self-reported tooth clenching had a slighter greater overbite (+0.3mm) at age 45 than those who did not. Additionally, those with signs of periodontal disease at age 38 had a slightly larger overjet (+0.5mm) at age 45 than those without disease. Sex differences were demonstrated with females having 0.6 mm larger overjet, and 0.4 mm overbite at age 45. CONCLUSIONS: Overall, overjet values tend to be higher during mid-adulthood than during adolescence, while the converse is true for overbite. There appears to be a degree of sexual dimorphism in overjet and overbite values later in life. CLINICAL SIGNIFICANCE: Incisor relationships change during the life course and are related to ageing, sex, periodontal health, and parafunctional habits. Clinicians and educators should be aware of these changes when making treatment decisions that alter incisor relationship.
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The Dunedin study after half a century: reflections on the past, and course for the future | 2022
Poulton, Richie. Guiney, Hayley. Ramrakha, Sandhya. Moffitt, Terrie E.
Journal of the Royal Society of New Zealand, 2022, 1-20.
https://doi.org/10.1080/03036758.2022.2114508
Our ref: NZ98
Over the last 50 years Dunedin Study researchers have published more than 1400 peer-reviewed journal articles, books, and reports on many aspects of human health and development. In this 50th anniversary piece we reflect on (i) our historical roots and necessary re-invention through time; (ii) the underpinning principles that have contributed to our success; (iii) some selected examples of high-impact work from the behavioural, oral health, and respiratory domains; (iv) some of the challenges we have encountered over time and how to overcome these; and (vi) review where we see the Study going in the future. We aim to present some of the ‘back story’, which is typically undocumented and oft lost to memory, and thus focus on ‘know-how’. Our hope is to humanise our research, share insights, and to acknowledge the real heroes of the Study – the 1037 Study members, their families and their friends, who have collectively given so much, for so long, in the hope of helping others.
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Genomic and phenomic insights from an atlas of genetic effects on DNA methylation. | 2021
Min J.L., Hemani, G., Hannon, E.,
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Nature Genetics , 2021, 53 1311–1321.
https://doi.org/10.1038/s41588-021-00923-x
Link to full publication »
Our ref: RO781
Characterizing genetic influences on DNA methylation (DNAm) provides an opportunity to understand mechanisms underpinning gene regulation and disease. In the present study, we describe results of DNAm quantitative trait locus (mQTL) analyses on 32,851 participants, identifying genetic variants associated with DNAm at 420,509 DNAm sites in blood. We present a database of >270,000 independent mQTLs, of which 8.5% comprise long-range (trans) associations. Identified mQTL associations explain 15–17% of the additive genetic variance of DNAm. We show that the genetic architecture of DNAm levels is highly polygenic. Using shared genetic control between distal DNAm sites, we constructed networks, identifying 405 discrete genomic communities enriched for genomic annotations and complex traits. Shared genetic variants are associated with both DNAm levels and complex diseases, but only in a minority of cases do these associations reflect causal relationships from DNAm to trait or vice versa, indicating a more complex genotype–phenotype map than previously anticipated.
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A deep-learning system for the assessment of cardiovascular disease risk via the measurement of retinal vessel calibres. | 2021
Cheung, CL., Xu D., Cheng., C.,
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Nature Biomedical Engineering, 2021, 5 498-508.
https://doi.org/10.1038/s41551-020-00626-4
Link to full publication »
Our ref: RO780
Retinal blood vessels provide information on the risk of cardiovascular disease (CVD). Here, we report the development and validation of deep-learning models for the automated measurement of retinal-vessel calibre in retinal photographs, using diverse multiethnic multicountry datasets that comprise more than 70,000 images. Retinal-vessel calibre measured by the models and by expert human graders showed high agreement, with overall intraclass correlation coefficients of between 0.82 and 0.95. The models performed comparably to or better than expert graders in associations between measurements of retinal-vessel calibre and CVD risk factors, including blood pressure, body-mass index, total cholesterol and glycated-haemoglobin levels. In retrospectively measured prospective datasets from a population-based study, baseline measurements performed by the deep-learning system were associated with incident CVD. Our findings motivate the development of clinically applicable explainable end-to-end deep-learning systems for the prediction of CVD on the basis of the features of retinal vessels in retinal photographs.
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Are macular drusen in midlife a marker of accelerated biological ageing? | 2021
Graham A Wilson, Kirsten Cheyne, Sandhya Ramrakha, Antony Ambler, Gavin SW Tan,
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Clinical and Experimental Optometry, 2021, 1-6.
https://doi.org/10.1080/08164622.2021.2012428
Our ref: RO770
Clinical relevance: Macular drusen are associated with age-related maculopathy but are not an ocular manifestation or biomarker of systemic ageing.
Background: Macular drusen are the first sign of age-related maculopathy, an eye disease for which age is the strongest risk factor. The aim of this cohort study was to investigate whether macular drusen in midlife – a sign of the earliest stages of age-related macular degeneration (AMD) – are
associated with accelerated biological ageing more generally.
Methods: Members of the long-running Dunedin Multidisciplinary Health and Development Study (hereafter the Dunedin Study, n = 1037) underwent retinal photography at their most recent assessment at the age of 45 years. Images were graded for the presence of AMD using a simplified
scale from the Age-Related Eye Disease Study (AREDS). Accelerated ageing was assessed by (i) a measure of Pace of Ageing defined from a combination of clinical and serum biomarkers obtained at ages 26, 32, 38, and 45 years and (ii) Facial Ageing, defined from photographs obtained at age 38 and 45 years.
Results: Of the 938 participants who participated at the age 45 assessments, 834 had gradable retinal photographs, and of these 165 (19.8%) had macular drusen. There was no significant difference in Pace of Ageing (p = .743) or Facial Ageing (p = .945) among participants with and without macular drusen.
Conclusions: In this representative general population sample, macular drusen in midlife were not associated with accelerated ageing. Future studies tracking longitudinal changes in drusen number and severity at older ages may reveal whether drusen are a biomarker of accelerated ageing.
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Does having children affect women's oral health? A longitudinal study | 2021
Morelli, E. L., Broadbent, J. M., Knight,
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J Public Health Dentistry, 2021, .
https://doi.org/10.1111/jphd.12466
Link to full publication »
Our ref: RO769
BACKGROUND: Many believe women's oral health deteriorates as a result of having children. If so, such associations should exist among women but not among men. The aims of this study were to investigate whether number of children is associated with experience of dental disease and tooth loss among both men and women and to examine whether this association is affected by other variables of interest. METHODS: This study used data from the Dunedin Multidisciplinary Health and Development study, a longitudinal study of 1037 individuals (48.4% female) born from April 1972 to March 1973 in Dunedin, New Zealand, who have been examined repeatedly from birth to age 45 years. RESULTS: Data were available for 437 women and 431 men. Those with low educational attainment were more likely to have more children and began having children earlier in life. Having more children was associated with experiencing more dental caries and tooth loss by age 45, but this association was dependent on the age at which the children were had. Those entering parenthood earlier in life (by age 26) had poorer dental health than those entering parenthood later in life, or those without children. There was no association between number of children and periodontal attachment loss (PAL). Low educational attainment, poor plaque control, never routine dental attendance, and smoking (for PAL) were associated with PAL, caries experience, and tooth loss. CONCLUSIONS: Social factors associated with both the timing of reproductive patterns and health behaviors influence the risk of dental disease and its management.
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Midlife Cardiovascular Fitness Is Reflected in the Brain's White Matter | 2021
d'Arbeloff, T., Elliott, M. L., Knodt,
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Frontiers in Aging Neuroscience, 2021, 13 .
https://doi.org/10.3389/fnagi.2021.652575
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Our ref: RO768
Disappointing results from clinical trials designed to delay structural brain decline and the accompanying increase in risk for dementia in older adults have precipitated a shift in testing promising interventions from late in life toward midlife before irreversible damage has accumulated. This shift, however, requires targeting midlife biomarkers that are associated with clinical changes manifesting only in late life. Here we explored possible links between one putative biomarker, distributed integrity of brain white matter, and two intervention targets, cardiovascular fitness and healthy lifestyle behaviors, in midlife. At age 45, fractional anisotropy (FA) derived from diffusion weighted MRI was used to estimate the microstructural integrity of distributed white matter tracts in a population-representative birth cohort. Age-45 cardiovascular fitness (VO2Max; N = 801) was estimated from heart rates obtained during submaximal exercise tests; age-45 healthy lifestyle behaviors were estimated using the Nyberg Health Index (N = 854). Ten-fold cross-validated elastic net predictive modeling revealed that estimated VO2Max was modestly associated with distributed FA. In contrast, there was no significant association between Nyberg Health Index scores and FA. Our findings suggest that cardiovascular fitness levels, but not healthy lifestyle behaviors, are associated with the distributed integrity of white matter in the brain in midlife. These patterns could help inform future clinical intervention research targeting ADRDs.
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Association of subcortical gray-matter volumes with life-course-persistent antisocial behavior in a population- representative longitudinal birth cohort | 2021
Carlisi, Christina O., Moffitt, Terrie E., Knodt,
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Development and Psychopathology, 2021, 1-11.
10.1017/s0954579421000377
Link to full publication »
Our ref: RO767
Neuropsychological evidence supports the developmental taxonomy theory of antisocial behavior, suggesting that abnormal brain development distinguishes life-course-persistent from adolescence-limited antisocial behavior. Recent neuroimaging work confirmed that prospectively- measured life-course-persistent antisocial behavior is associated with differences in cortical brain structure. Whether this extends to subcortical brain structures remains uninvestigated. This study compared subcortical gray-matter volumes between 672 members of the Dunedin Study previously defined as exhibiting life-course-persistent, adolescence-limited or low-level antisocial behavior based on repeated assessments at ages 7–26 years. Gray-matter volumes of 10 subcortical structures were compared across groups. The lifecourse- persistent group had lower volumes of amygdala, brain stem, cerebellum, hippocampus, pallidum, thalamus, and ventral diencephalon compared to the low-antisocial group. Differences between life-course-persistent and adolescence-limited individuals were comparable in effect size to differences between life-course-persistent and low-antisocial individuals, but were not statistically significant due to less statistical power. Gray-matter volumes in adolescence-limited individuals were near the norm in this population-representative cohort and similar to volumes in low-antisocial individuals. Although this study could not establish causal links between brain volume and antisocial behavior, it constitutes new biological evidence that all people with antisocial behavior are not the same, supporting a need for greater developmental and diagnostic precision in clinical, forensic, and policy-based interventions.
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Vital personality scores and healthy aging: Life-course associations and familial transmission | 2021
J. Wertz, S. Israel, L. Arseneault, D. W. Belsky, K. J. Bourassa,
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Social Science & Medicine, 2021, 285 .
https://doi.org/10.1016/j.socscimed.2021.114283
Our ref: RO766
Objectives Personality traits are linked with healthy aging, but it is not clear how these associations come to manifest across the life-course and across generations. To study this question, we tested a series of hypotheses about (a) personality-trait prediction of markers of healthy aging across the life-course, (b) developmental origins, stability and change of links between personality and healthy aging across time, and (c) intergenerational transmission of links between personality and healthy aging. For our analyses we used a measure that aggregates the contributions of Big 5 personality traits to healthy aging: a “vital personality” score. Methods Data came from two population-based longitudinal cohort studies, one based in New Zealand and the other in the UK, comprising over 6000 study members across two generations, and spanning an age range from birth to late life. Results Our analyses revealed three main findings: first, individuals with higher vital personality scores engaged in fewer health-risk behaviors, aged slower, and lived longer. Second, individuals’ vital personality scores were preceded by differences in early-life temperament and were relatively stable across adulthood, but also increased from young adulthood to midlife. Third, individuals with higher vital personality scores had children with similarly vital partners, promoted healthier behaviors in their children, and had children who grew up to have more vital personality scores themselves, for genetic and environmental reasons. Conclusion Our study shows how the health benefits associated with personality accrue throughout the life-course and across generations.
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Eleven genomic loci affect plasma levels of chronic inflammation marker soluble urokinase-type plasminogen activator receptor | 2021
J. Dowsett, E. Ferkingstad, L. J. H. Rasmussen, L. W. Thørner, M. K. Magnússon,
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Communications Biology, 2021, 4(1), 655.
https://doi.org/10.1038/s42003-021-02144-8
Our ref: RO765
Soluble urokinase-type plasminogen activator receptor (suPAR) is a chronic inflammation marker associated with the development of a range of diseases, including cancer and cardiovascular disease. The genetics of suPAR remain unexplored but may shed light on the biology of the marker and its connection to outcomes. We report a heritability estimate of 60% for the variation in suPAR and performed a genome-wide association meta-analysis on suPAR levels measured in Iceland (N = 35,559) and in Denmark (N = 12,177). We identified 13 independently genome-wide significant sequence variants associated with suPAR across 11 distinct loci. Associated variants were found in and around genes encoding uPAR (PLAUR), its ligand uPA (PLAU), the kidney-disease-associated gene PLA2R1 as well as genes with relations to glycosylation, glycoprotein biosynthesis, and the immune response. These findings provide new insight into the causes of variation in suPAR plasma levels, which may clarify suPAR’s potential role in associated diseases, as well as the underlying mechanisms that give suPAR its prognostic value as a unique marker of chronic inflammation.
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Changes to family structure, household composition and address among young New Zealanders: an update | 2021
McAnally, Helena M. Sligo, Judith L. Baxter, Joanne Tansley, Janine E. Bolton,
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Kōtuitui: New Zealand Journal of Social Sciences Online, 2021, .
10.1080/1177083x.2021.1957946
Link to full publication »
Our ref: NZ100
In this article, we describe the life-time family structures, living arrangements, and residential mobility of 612 15-year-old New Zealanders and consider the differences in experiences of children born to younger and older mothers. All participants had a parent who is a member of the Dunedin Multidisciplinary Health and Development Study. Maternal age at the participant’s birth ranged from 16.3 to 41.0 years. Data on young people’s lifetime care arrangements, household composition and shifts were collected from their primary caregiver via a life history calendar. Fewer than half lived in a household consisting of two biological parents and only a fifth had lived in a household consisting of only nuclear family members for all 15 years. Most also experienced multiple changes of address (median 6, range 1–27). Those born to older parents tended to have fewer changes to care arrangements and family structures but most young people experienced a substantial degree of change across their lives. These data indicate that complexity and change are normal in young New Zealanders’ living arrangements. We argue that conventional ideas about family structure should be re-examined.
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Linking stressful life events and chronic inflammation using suPAR (soluble urokinase plasminogen activator receptor) | 2021
Bourassa, K. J. Rasmussen, L. J. H. Danese, A. Eugen-Olsen, J. Harrington,
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Brain Behavior and Immunity, 2021, .
10.1016/j.bbi.2021.06.018
Link to full publication »
Our ref: RO764
Stressful life events have been linked to declining health, and inflammation has been proposed as a physiological mechanism that might explain this association. Using 828 participants from the Dunedin Longitudinal Study, we tested whether people who experienced more stressful life events during adulthood would show elevated systemic inflammation when followed up in midlife, at age 45. We studied three inflammatory biomarkers: C-reactive protein (CRP), interleukin-6 (IL-6), and a newer biomarker, soluble urokinase plasminogen activator receptor (suPAR), which is thought to index systemic chronic inflammation. Stressful life events were not associated with CRP or IL-6. However, people who experienced more stressful life events from age 38 to 44 had elevated suPAR at age 45, and had significantly greater increases in suPAR from baseline to follow-up across the same period. When examining stressful life events across the lifespan, both adverse childhood experiences (ACEs) and adult stressful life events were independently associated with suPAR at age 45. ACEs moderated the association of adult stressful life events and suPAR at age 45-children with more ACEs showed higher suPAR levels after experiencing stressful life events as adults. The results suggest systemic chronic inflammation is one physiological mechanism that could link stressful life events and health, and support the use of suPAR as a useful biomarker for such research.
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Do socially isolated children become socially isolated adults? | 2021
Lay-Yee, Roy; Matthews, Timothy; Moffitt, Terrie; Poulton, Richie; Caspi,
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Advances in Life Course Research, 2021, .
10.1016/j.alcr.2021.100419
Link to full publication »
Our ref: RO763
Social isolation - the lack of social contacts in number and frequency – has been shown to have a negative impact on health and well-being. Using group-based trajectory analysis of longitudinal data from a New Zealand birth cohort, we created a typology of social isolation based on onset during the life course and persistence into adulthood. We then characterized each type according to risk factors related to family environment and child behavior that have been shown previously to be associated with social isolation. Based on fit statistics and distinctness of trajectories we considered the four-class model to be the most appropriate: (1) ‘never isolated’ (71.6 % of the cohort), (2) ‘adult only’ (10.1 %), (3) ‘child only’ (14.3 %), and (4) ‘persistent isolation’ (4.0 %). Family-environmental factors – i.e. having a teen-aged mother, having a single parent, frequent changes in residence, or maltreatment – tended to be associated with both child and adult onset and persistence of social isolation, whereas child-behavioral factors – i.e. self-control or internalizing symptoms – applied more to the child onset of social isolation. Sensitivity analyses using empirically defined groups – based on 15 % ‘cut-offs’ for isolation in childhood and adulthood - produced similar life-course groupings and similar associations. Our findings provide insights into the development of social isolation and demonstrate the changeability of social isolation across almost four decades of the life span. They also suggest family-based and child-based interventions could address child onset and the persistence of social isolation into adulthood.
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Resource profile and user guide of the Polygenic Index Repository | 2021
Becker, J. Burik, C. A. P. Goldman, G. Wang, N. Jayashankar,
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Nature Human Behaviour, 2021, .
10.1038/s41562-021-01119-3
Link to full publication »
Our ref: RO762
Polygenic indexes (PGIs) are DNA-based predictors. Their value for research in many scientific disciplines is growing rapidly. As a resource for researchers, we used a consistent methodology to construct PGIs for 47 phenotypes in 11 datasets. To maximize the PGIs' prediction accuracies, we constructed them using genome-wide association studies-some not previously published-from multiple data sources, including 23andMe and UK Biobank. We present a theoretical framework to help interpret analyses involving PGIs. A key insight is that a PGI can be understood as an unbiased but noisy measure of a latent variable we call the 'additive SNP factor'. Regressions in which the true regressor is this factor but the PGI is used as its proxy therefore suffer from errors-in-variables bias. We derive an estimator that corrects for the bias, illustrate the correction, and make a Python tool for implementing it publicly available.
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Long-term Neural Embedding of Childhood Adversity in a Population-Representative Birth Cohort Followed for 5 Decades | 2021
Gehred, M. Z. Knodt, A. R. Ambler, A. Bourassa, K. J. Danese,
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Biological Psychiatry, 2021, 90(3), 182-193.
10.1016/j.biopsych.2021.02.971
Link to full publication »
Our ref: RO761
BACKGROUND: Childhood adversity has been previously associated with alterations in brain structure, but heterogeneous designs, methods, and measures have contributed to mixed results and have impeded progress in mapping the biological embedding of childhood adversity. We sought to identify long-term differences in structural brain integrity associated with childhood adversity. METHODS: Multiple regression was used to test associations between prospectively ascertained adversity during childhood and adversity retrospectively reported in adulthood with structural magnetic resonance imaging measures of midlife global and regional cortical thickness, cortical surface area, and subcortical gray matter volume in 861 (425 female) members of the Dunedin Study, a longitudinal investigation of a population-representative birth cohort. RESULTS: Both prospectively ascertained childhood adversity and retrospectively reported adversity were associated with alterations in midlife structural brain integrity, but associations with prospectively ascertained childhood adversity were consistently stronger and more widely distributed than associations with retrospectively reported childhood adversity. Sensitivity analyses revealed that these associations were not driven by any particular adversity or category of adversity (i.e., threat or deprivation) or by childhood socioeconomic disadvantage. Network enrichment analyses revealed that these associations were not localized but were broadly distributed along a hierarchical cortical gradient of information processing. CONCLUSIONS: Exposure to childhood adversity broadly is associated with widespread differences in midlife gray matter across cortical and subcortical structures, suggesting that biological embedding of childhood adversity in the brain is long lasting, but not localized. Research using retrospectively reported adversity likely underestimates the magnitude of these associations. These findings may inform future research investigating mechanisms through which adversity becomes embedded in the brain and influences mental health and cognition.
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Autistic traits are associated with faster pace of aging: Evidence from the Dunedin study at age 45 | 2021
Mason, D. Ronald, A. Ambler, A. Caspi, A. Houts,
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Autism Research, 2021, .
10.1002/aur.2534
Link to full publication »
Our ref: RO760
Growing evidence indicates that the defining characteristics of autism spectrum disorder (ASD) are distributed throughout the general population; hence, understanding the correlates of aging in people with high autistic traits could shed light on ASD and aging. 915 members of the Dunedin longitudinal birth cohort completed a measure of autistic traits at age 45. A composite measure of the "pace of aging" was derived by tracking the decline in 19 biomarkers across ages 26, 32, 38, and 45 years. Facial age was also assessed. Reports of perceived health were collected from participants themselves, informants, and interviewers. Higher self-reported autistic traits significantly correlated with a faster pace of aging, older facial age, and poorer self-, informant-, and interviewer-rated health. After control for sex, SES and IQ, autistic traits were significantly associated with each variable: pace of aging (beta = 0.09), facial age (beta = 0.08), self- (beta = -0.15), informant (beta = -0.12), and interviewer-rated (beta = -0.17) health. Autistic traits measured at age 45 are associated with faster aging. Participants with high autistic traits appear to be more vulnerable to poor health outcomes, as previously reported for those clinically diagnosed with ASD. Therefore, autistic traits may have important health implications. Replicating these findings in samples of autistic people is needed to identify the mechanism of their effect on aging and physical health to improve outcomes for those with ASD diagnoses or high autistic traits. LAY SUMMARY: The role that autistic traits have in relation to health outcomes has not been investigated. We looked at how physical health and aging (measured with self-reported questions and decline in multiple biological measures) were related to autistic traits (measured with a questionnaire, at age 45). We found that higher autistic traits were associated with poorer reports of physical health, and a faster pace of aging. This suggests that both those with autism and those with higher autistic traits may be more likely to experience poorer health outcomes.
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Understanding the data-sharing debate in the context of Aotearoa/New Zealand: a narrative review on the perspectives of funders, publishers/journals, researchers, participants and Māori collectives | 2021
Reeves, Jane; Treharne, Gareth J.; Theodore, Reremoana; Edwards, Will; Ratima,
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Kōtuitui: New Zealand Journal of Social Sciences Online, 2021, 1-23.
10.1080/1177083x.2021.1922465
Link to full publication »
Our ref: NZ99
This review outlines current debates about the sharing of research data, with a focus on relevance for Aotearoa/New Zealand. Recent years have seen increasingly frequent calls for public sharing of data from funders and publishers/journals in particular. Past research has suggested that researchers tend to agree that any detriments of data-sharing are outweighed by benefits for transparency and progress. We summarise trends across past research into perspectives of funders, publishers/journals, and researchers on data-sharing before raising three considerations. Firstly, past research on data-sharing has tended to overlook the potential implications of data-sharing for participants. We review the small body of research on participant perspectives. This research has conceptualised participants as a homogenous group without theorising how participants make sense of data-sharing. Secondly, perspectives on data-sharing vary depending on the methodology being applied, and we raise some specific considerations when datasharing is proposed in long-term longitudinal research such as the Dunedin Study. Thirdly, Indigenous perspectives on data-sharing must be central to all research into data-sharing with any of the stakeholder groups, and we review existing research on data sovereignty in relation to data-sharing in Aotearoa/New Zealand and globally. We conclude by summarising a series of tensions between stakeholders in the data-sharing debate.
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Genetic Association Study of Childhood Aggression across raters, instruments and age | 2021
Ip, Hill F. Van Der Laan, Camiel M. Krapohl, Eva M. L. Brikell, Isabell Cristina,
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Translational Psychiatry, 2021, .
https://doi.org/10.1101/854927
Our ref: RO759
Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association meta-analysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data – i.e. within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGGoverall) was 3.31% (SE=0.0038). We found no genome-wide significant SNPs for AGGoverall. The gene-based analysis returned three significant genes: ST3GAL3 (P=1.6E-06), PCDH7 (P=2.0E-06) and IPO13 (P=2.5E-06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations (rg) among rater-specific assessment of AGG ranged from rg =0.46 between self- and teacher-assessment to rg =0.81 between mother- and teacher-assessment. We obtained moderate to strong rg’s with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range |rg| : 0.19 – 1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (rg =~ −0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range |rg| : 0.46 – 0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG.
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Lower Cardiovascular Reactivity Is Associated With More Childhood Adversity and Poorer Midlife Health: Replicated Findings From the Dunedin and MIDUS Cohorts | 2021
Bourassa KJ, Moffitt TE, Harrington HL, Houts RM, Poulton R,
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Clinical Psychological Science, 2021, 1-18.
https://doi.org/10.1177%2F2167702621993900
Link to full publication »
Our ref: RO758
Cardiovascular reactivity has been proposed as a biomarker linking childhood adversity and poorer health. In the current study, we examined the association of childhood adversity, cardiovascular reactivity, and health in the Dunedin Multidisciplinary Health and Development Study (n = 922) and Midlife in the United States (MIDUS) studies (n = 1,015). In both studies, participants who experienced more childhood adversity had lower cardiovascular reactivity. In addition, people with lower cardiovascular reactivity had poorer self-reported health and greater inflammation. Dunedin participants with lower cardiovascular reactivity were aging biologically faster, and MIDUS participants with lower heart rate reactivity had increased risk of early mortality. Cardiovascular reactivity was not associated with hypertension in either study. Results were partially accounted for by greater reactivity among more conscientious, less depressed, and higher functioning participants. These results suggest that people who experienced childhood adversity have a blunted physiological response, which is associated with poorer health. The findings highlight the importance of accounting for individual differences when assessing cardiovascular reactivity using cognitive stressor tasks.
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Association of History of Psychopathology With Accelerated Aging at Midlife | 2021
Wertz, Jasmin, Avshalom Caspi, Antony Ambler, Jonathan Broadbent,
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JAMA Psychiatry, 2021, .
10.1001/jamapsychiatry.2020.4626
Link to full publication »
Our ref: RO757
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.
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Age- and sex-specific visceral fat reference cutoffs and their association with cardio-metabolic risk | 2021
Kim Meredith-Jones, Rachael Taylor, Rachel Brown, Rebecca McLay-Cooke, Lara Vlietstra,
... Show all »
International Journal of Obesity, 2021, 45 808-817.
https://doi.org/10.1038/s41366-021-00743-3
Link to full publication »
Our ref: RO753
Background
Although excess visceral fat (VAT) is associated with numerous cardio-metabolic risk factors, measurement of this fat depot has historically been difficult. Recent dual X-ray absorptiometry approaches have provided an accessible estimate of VAT that has shown acceptable validity against gold standard methods. The aims of this study were to (i) evaluate DXA measured VAT as a predictor of elevated blood lipids and blood pressure and (ii) calculate thresholds associated with these cardio-metabolic risk factors.
Subjects/methods
The sample comprised 1482 adults (56.4% women) aged 18–66 years. Total body scans were performed using a GE Lunar Prodigy, and VAT analyses were enabled through Corescan software (v 16.0). Blood pressure and blood lipids were measured by standard procedures. Regression models assessed how VAT mass was associated with each cardio-metabolic risk factor compared to other body composition measures. Measures of sensitivity and specificity were used to determine age- and sex-specific cut points for VAT mass associated with high cardio-metabolic risk.
Results
Similar to waist circumference, VAT mass was a strong predictor of cardio-metabolic risk especially in men over age 40. Four cut-offs for VAT mass were proposed, above which the cardio-metabolic risk increased: 700 g in women <40 yrs; 800 g in women 40+ yrs; 1000g in men <40 yrs; and 1200 g in men 40+ yrs. In general, these cut-offs discriminated well between those with high and low cardio-metabolic risk.
Conclusions
In both sexes, DXA measured VAT was associated with traditional cardio-metabolic risk factors, particularly high blood pressure in those 40+ yrs and low HDL < 40 yrs. These reference values provide a simple, accessible method to assess cardio-metabolic risk in adults.
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Population versus individual prediction of poor health from Adverse Childhood Experiences (ACEs) screening | 2021
Baldwin, J. R., Caspi, A., Meehan,
... Show all »
JAMA Pediatrics, 2021, .
https://doi.org/10.1001/jamapediatrics.2020.5602
Link to full publication »
Our ref: RO752
Importance: Adverse childhood experiences (ACEs) are well-established risk factors for health problems in the population. However, it is not known whether screening for ACEs can accurately identify individuals who develop later health problems.
Objective: To test the predictive accuracy of ACE screening for later health problems.
Design: Two birth cohorts: The Environmental Risk (E-Risk) Longitudinal Twin Study followed participants born in 1994-1995 until age 18 (2012-2014), and the Dunedin Multidisciplinary Health and Development Study followed participants born in 1972-1973 until age 45 (2017-2019).
Setting: Population-based cohorts from the United Kingdom and New Zealand.
Participants: 2,232 participants in E-Risk and 1,037 participants in Dunedin.
Exposure: ACEs were measured prospectively in childhood through repeated interviews and observations in both cohorts. ACEs were also measured retrospectively in the Dunedin cohort through interviews at age 38.
Main outcomes and measures: Health outcomes were assessed at age 18 in E-Risk and age 45 in Dunedin. Mental health problems were assessed through clinical interviews using the Diagnostic Interview Schedule. Physical health problems were assessed through interviews, anthropometric measurements, and blood collection.
Results: Of 2,232 E-Risk participants and 1,037 Dunedin participants, 2,009 and 928 were included in the analysis, respectively. In E-Risk, children with higher ACE scores had greater risk of later health problems (Relative Risks=1.14 [95% CI=1.10-1.18] for any mental health problem and 1.09 [95% CI=1.07-1.12] for any physical health problem per each additional ACE). ACE scores were associated with health problems independently of other information typically available to clinicians (i.e., sex, socioeconomic disadvantage, and history of health problems). However, ACE scores had poor accuracy in predicting an individual’s risk of later health problems (Area Under the ROC Curve for any mental health problem=0.58 [95% CI=0.56-0.61] and 0.60 [95% CI=0.58-0.63] for any physical health problem vs 0.50 for chance prediction). Findings were consistent in the Dunedin cohort using both prospective and retrospective ACE measures.
Conclusions and Relevance: While ACE scores can forecast average group differences in health, they have poor accuracy in predicting an individual’s risk of later health problems. Therefore, targeting interventions based on ACE screening is likely to be ineffective in preventing poor health.
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Disparities in the pace of biological aging among midlife adults of the same chronological age have implications for future frailty risk and policy | 2021
Maxwell L. Elliott, Avshalom Caspi, Renate M. Houts, Antony Ambler, Jonathan M. Broadbent,
... Show all »
Nature Aging, 2021, 1 295–308.
https://doi.org/10.1038/s43587-021-00044-4
Link to full publication »
Our ref: RO751
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 1,037 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 appearances 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.
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DNA methylation signatures of aggression and closely related constructs: A meta-analysis of epigenome-wide studies across the lifespan | 2021
van Dongen, J. Hagenbeek, F. A. Suderman, M. Roetman, P. J. Sugden,
... Show all »
Molecular Psychiatry, 2021, .
10.1038/s41380-020-00987-x
Link to full publication »
Our ref: RO750
DNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N = 15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha = 1.2 x 10(-7); Bonferroni correction). In cord blood samples of 2425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83% of these sites showed the same direction of association with childhood aggression (r = 0.74, p = 0.006) but no epigenome-wide significant sites were found. Top-sites (48 at a false discovery rate of 5% in the peripheral blood meta-analysis or in a combined meta-analysis of peripheral blood and cord blood) have been associated with chemical exposures, smoking, cognition, metabolic traits, and genetic variation (mQTLs). Three genes whose expression levels were associated with top-sites were previously linked to schizophrenia and general risk tolerance. At six CpGs, DNA methylation variation in blood mirrors variation in the brain. On average 44% (range = 3-82%) of the aggression-methylation association was explained by current and former smoking and BMI. These findings point at loci that are sensitive to chemical exposures with potential implications for neuronal functions. We hope these results to be a starting point for studies leading to applications as peripheral biomarkers and to reveal causal relationships with aggression and related traits.
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Childhood self-control forecasts the pace of midlife aging and preparedness for old age | 2021
Richmond-Rakerd, L. S. Caspi, A. Ambler, A. d'Arbeloff, T. de Bruine,
... Show all »
PNAS, 2021, 118(3), .
https://doi.org/10.1073/pnas.2010211118
Link to full publication »
Our ref: RO748
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.
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Early-onset and recurrent depression in parents increases risk of intergenerational transmission to adolescent offspring | 2021
Jaffee, S. R. Sligo, J. L. McAnally, H. M. Bolton, A. E. Baxter,
... Show all »
Journal of Child Psychology and Psychiatry, 2021, .
10.1111/jcpp.13356
Link to full publication »
Our ref: RO746
BACKGROUND: To assess whether the age-of-onset or the recurrence of parents' major depressive disorder (MDD), measured prospectively in a longitudinal birth cohort study, predicted offspring depression at age 15. METHODS: A two-generation study of New Zealanders, with prospective, longitudinal data in the parents' generation (n = 375) and cross-sectional data from their adolescent offspring (n = 612). Parent and offspring depression was measured with structured clinical interviews. Parent depression was measured at six time points from age 11 to 38 years. Adolescent offspring depression was measured at age 15. RESULTS: Compared to adolescents whose parents were never depressed, those whose parents met criteria for MDD more than once and those whose parents first met criteria before adulthood had more symptoms of depression. The combination of early-onset and recurrent depression in parents made adolescents particularly vulnerable; their odds of meeting criteria for MDD were 4.21 times greater (95% CI = 1.57-11.26) than adolescents whose parents were never depressed. The strength of the intergenerational effect did not vary as a function of parent or offspring sex. The prevalence of adolescent depression was 2.5 times higher in the offspring than at age 15 in the parents' generation. CONCLUSIONS: Recurrent depression in both fathers and mothers increases offspring risk for depression, particularly when it starts in childhood or adolescence, but a single lifetime episode does not. Health practitioners should be aware of age-of-onset and course of depression in both parents when assessing their children's risk for depression.
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Investigating the Genetic Architecture of Non-Cognitive Skills Using GWAS-by-Subtraction | 2021
Perline A. Demange, Margherita Malanchini, Travis T. Mallard, Pietro Biroli, Simon R. Cox,
... Show all »
Nature Genetics, 2021, 53 35-44.
https://doi.org/10.1038/s41588-020-00754-2
Link to full publication »
Our ref: RO745
Little is known about the genetic architecture of traits affecting educational attainment other than cognitive ability. We used genomic structural equation modeling and prior genome-wide association studies (GWASs) of educational attainment (n = 1,131,881) and cognitive test performance (n = 257,841) to estimate SNP associations with educational attainment variation that is independent of cognitive ability. We identified 157 genome-wide-significant loci and a polygenic architecture accounting for 57% of genetic variance in educational attainment. Noncognitive genetics were enriched in the same brain tissues and cell types as cognitive performance, but showed different associations with gray-matter brain volumes. Noncognitive genetics were further distinguished by associations with personality traits, less risky behavior and increased risk for certain psychiatric disorders. For socioeconomic success and longevity, noncognitive and cognitive-performance genetics demonstrated associations of similar magnitude. By conducting a GWAS of a phenotype that was not directly measured, we offer a view of genetic architecture of noncognitive skills influencing educational success. Genomic structural equation modeling of genome-wide association data for educational attainment and cognitive test performance is used to estimate the genetic component of variation in educational attainment that is independent of cognitive ability. The study finds that noncognitive skills account for 57% of genetic variation in educational attainment.
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Long-Term Survival of Enamel-Defect-Affected Teeth | 2020
Hong C.L., Broadbent J.M. and Thomson W.M.
Caries Research, 2020, 54 350-357.
https://doi.org/10.1159/000510304
Link to full publication »
Our ref: RO754
There has been considerable research focussed on the occurrence and aetiology of developmental defects of enamel, but less is known about the extent to which enamel-defect-affected teeth may be at greater risk for dental caries. The Dunedin Multidisciplinary Health and Development Study is a prospective cohort study of 1,037 children born in Dunedin, New Zealand, between April 1, 1972, and March 31, 1973. Participants were examined for the presence of developmental defects of enamel at the age of 9 years and then repeatedly for the occurrence of dental caries through to the age of 45 years. After controlling for confounding variables, incisor teeth affected by demarcated opacities at the age of 9 were 3.4 times more likely to be restored than teeth unaffected by defects. Incisors with diffuse opacities and hypoplasia or combinations of defects were 2.8 times more likely to be restored. Molars with enamel defects of any type did not have any significantly different risk for being subsequently restored or lost due to caries than unaffected molars, except those affected by diffuse opacities, which were at 0.4 times the risk of being lost due to caries. Dental clinicians should be aware that enamel-defect-affected teeth are not necessarily at greater risk for tooth loss due to caries in the long term, but permanent incisors affected by enamel defects are at higher risk of receiving restorative intervention.
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Psychotic experiences and schizotypy in early adolescence predict subsequent suicidal ideation trajectories and suicide attempt outcomes from 18- to 38-years | 2020
Kirstie J. M. O’Hare, Richie Poulton, Richard J. Linscott
Schizophrenia Bulletin, 2020, .
https://doi.org/10.1093/schbul/sbaa151
Link to full publication »
Our ref: RO741
Subclinical risk markers for schizophrenia predict suicidality, but little is known about the nature of the relationship. Suicidal ideation is often considered homogenous, but distinguishing passive from active ideation (i.e. thoughts of death vs thoughts of killing oneself) and different temporal patterns may further understanding of risk factors. We tested whether schizotypy and psychotic experiences (PE) in early adolescence predict subsequent growth trajectories of suicidal ideation and suicide attempt outcomes. Participants were 1037 members of the population-representative Dunedin Study cohort. PE was measured at 11 years; schizotypy at 13 and 15 years. Outcomes were passive and active suicidal ideation, and suicide attempt, measured at 18, 21, 26, 32, and 38 years. Passive ideation was best represented by two trajectories, including persistent and transient ideation classes. Schizotypy predicted membership in the smaller persistent class (OR = 1.21, p = .041), whereas PE was not associated with class membership. Probability of suicide attempt was 13.8% in the persistent ideation class, compared to 1.8% in the transient class. Active ideation was best represented by a one-class model, the intercept of which was predicted by schizotypy (OR = 1.23, p = .015). Suicide attempts were predicted by schizotypy (OR = 1.53, p = .040) and PE (OR = 3.42, p = .046), and this was partially mediated by indirect effects via the active ideation trajectory. Findings indicate adolescent schizotypy and PE are related to subsequent suicidal ideation and attempts. Suicidal ideation is heterogenous, and schizotypy is specifically related to a persistent passive ideation subgroup.
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Childhood disadvantage and adolescent socioemotional wellbeing as predictors of future parenting behaviour | 2020
McAnally, H. M. Iosua, E. Sligo, J. L. Belsky, J. Spry,
... Show all »
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,
... Show all »
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,
... Show all »
Aging, 2020, 12(20), .
https://doi.org/10.18632/aging.104112
Link to full publication »
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,
... Show all »
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,
... Show all »
Patterns, 2020, 1(2), .
https://doi.org/10.1016/j.patter.2020.100014
Link to full publication »
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,
... Show all »
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,
... Show all »
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
Link to full publication »
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,
... Show all »
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
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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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