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Richie Poulton

Publications and source records attributed to Richie Poulton.

At least 19 recordsLinked to original sources

An Updated Polygenic Index Repository: Expanded Phenotypes, New Cohorts, and Improved Causal Inference.

Polygenic indexes (PGIs) - DNA-based predictors of individual phenotypes - have become essential tools across biomedical and social sciences. We introduce Version 2 of the Polygenic Index Repository, which expands phenotype coverage from 47 to 61, increases the number of participating datasets from 11 to 20, and adopts a more consistent and improved methodology for PGI construction. For 16 phenotypes, we leverage summary statistics from an updated GWAS meta-analysis with greater statistical power compared to the original release, thereby improving the PGI's predictive power. To improve power for family-based analyses, we provide imputed parental PGIs in all datasets with first-degree relatives and offer a framework for interpreting results from analyses that control for parental PGIs. We illustrate the utility of parental PGIs using two applications: (1) comparing PGI associations with and without parental PGI controls for all phenotypes in two Repository datasets with family data, and (2) for BMI and diastolic blood pressure, exploring the contribution of causal versus non-causal components of PGI associations to the imperfect portability of PGIs across subgroups within a genetic ancestry. Collectively, the updates enhance predictive performance, broaden the Repository's scope, and introduce novel resources that reduce confounding bias and improve interpretability.

Journal Article↗

Characterizing midlife-onset alcohol dependence: Implications for etiology, prevention, and healthy aging.

We evaluated the developmental epidemiology of midlife-onset alcohol dependence (AD) in the Dunedin Study (N=1,037), a population-representative cohort followed across five decades. At ages 18, 21, 26, 32, 38, and 45, past-year AD prevalence was 11.0%, 18.4%, 13.6%, 8.1%, 9.6%, and 11.3%, respectively. As expected, relative to never-diagnosed individuals, those with early-onset AD (first diagnosis: age-18 or age-21, prevalence=22.9%) were distinguished by a range of early-life and adult correlates. Individuals with midlife-onset AD (first diagnosis: age-38 or age-45, prevalence=5.6%) were distinguished by fewer early-life correlates, but exhibited a family history of AD, and adolescent dysregulation and marijuana-use. They were characterized by an array of adult correlates, including internalizing disorders, mental-health treatment-contact, criminal-behavior, perceived-stress, coping-by-drinking, lower likelihood of marriage and parenthood, and reduced preparedness for old age. They also experienced more adult alcohol-related impairment than the early-onset group. Results can guide efforts to reduce midlife alcohol-related problems and support healthy aging.

Journal Article↗

Improving risk indexes for Alzheimer's disease and related dementias for use in midlife.

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

Alzheimer’s disease↗

Childhood maltreatment predicts adult inflammation in a life-course study.

Stress in early life has been associated with insufficient glucocorticoid signaling in adulthood, possibly affecting inflammation processes. Childhood maltreatment has been linked to increased risk of adult disease with potential inflammatory origin. However, the impact of early life stress on adult inflammation is not known in humans. We tested the life-course association between childhood maltreatment and adult inflammation in a birth cohort followed to age 32 years as part of the Dunedin Multidisciplinary Health and Development Study. Regression models were used to estimate the effect of maltreatment on inflammation, adjusting for co-occurring risk factors and potential mediating variables. Maltreated children showed a significant and graded increase in the risk for clinically relevant C-reactive protein levels 20 years later, in adulthood [risk ratio (RR)=1.80, 95% confidence interval (CI)=1.26-2.58]. The effect of childhood maltreatment on adult inflammation was independent of the influence of co-occurring early life risks (RR=1.58, 95% CI=1.08-2.31), stress in adulthood (RR=1.64, 95% CI=1.12-2.39), and adult health and health behavior (RR=1.76, 95% CI=1.23-2.51). More than 10% of cases of low-grade inflammation in the population, as indexed by high C-reactive protein, may be attributable to childhood maltreatment. The association between maltreatment and adult inflammation also generalizes to fibrinogen and white blood cell count. Childhood maltreatment is a previously undescribed, independent, and preventable risk factor for inflammation in adulthood. Inflammation may be an important developmental mediator linking adverse experiences in early life to poor adult health.

Adult↗

Generalized anxiety disorder and depression: childhood risk factors in a birth cohort followed to age 32.

BACKGROUND: The close association between generalized anxiety disorder (GAD) and major depressive disorder (MDD) prompts questions about how to characterize them in future diagnostic systems. We tested whether risk factors for MDD and GAD are similar or different. METHOD: The representative 1972-73 Dunedin birth cohort of 1037 males and females was followed to age 32 with 96% retention. Adult GAD and MDD were diagnosed at ages 18, 21, 26, and 32 years, and juvenile anxiety/depression were also taken into account. Thirteen prospective risk measures indexed domains of family history, adverse family environment, childhood behavior, and adolescent self-esteem and personality traits. RESULTS: Co-morbid MDD+GAD was antedated by highly elevated risk factors broadly across all domains. MDD+GAD was further characterized by the earliest onset, most recurrence, and greatest use of mental health services and medication. Pure GAD had levels of risk factors similar to the elevated levels for co-morbid MDD+GAD; generally, pure MDD did not. Pure GAD had risks during childhood not shared by pure MDD, in domains of adverse family environment (low SES, somewhat more maltreatment) and childhood behavior (internalizing problems, conduct problems, somewhat more inhibited temperament). Pure MDD had risks not shared by pure GAD, in domains of family history (of depression) and personality (low positive emotionality). CONCLUSIONS: Specific antecedent risk factors for pure adult MDD versus GAD may suggest partly different etiological pathways. That GAD and co-morbid MDD+GAD share many risk markers suggests that the presence of GAD may signal a pathway toward relatively more severe internalizing disorder.

Adolescent↗

Associations between respiratory symptoms, lung function and gastro-oesophageal reflux symptoms in a population-based birth cohort.

BACKGROUND: Several studies have reported an association between asthma and gastro-oesophageal reflux, but it is unclear which condition develops first. The role of obesity in mediating this association is also unclear. We explored the associations between respiratory symptoms, lung function, and gastro-oesophageal reflux symptoms in a birth cohort of approximately 1000 individuals. METHODS: Information on respiratory symptoms, asthma, atopy, lung function and airway responsiveness was obtained at multiple assessments from childhood to adulthood in an unselected birth cohort of 1037 individuals followed to age 26. Symptoms of gastro-oesophageal reflux and irritable bowel syndrome were recorded at age 26. RESULTS: Heartburn and acid regurgitation symptoms that were at least "moderately bothersome" at age 26 were significantly associated with asthma (odds ratio = 3.2; 95% confidence interval = 1.6-6.4), wheeze (OR = 3.5; 95% CI = 1.7-7.2), and nocturnal cough (OR = 4.3; 95% CI = 2.1-8.7) independently of body mass index. In women reflux symptoms were also associated with airflow obstruction and a bronchodilator response to salbutamol. Persistent wheezing since childhood, persistence of asthma since teenage years, and airway hyperresponsiveness since age 11 were associated with a significantly increased risk of heartburn and acid regurgitation at age 26. There was no association between irritable bowel syndrome and respiratory symptoms. CONCLUSION: Reflux symptoms are associated with respiratory symptoms in young adults independently of body mass index. The mechanism of these associations remains unclear.

Adolescent↗

Adiposity, asthma, and airway inflammation.

BACKGROUND: Several studies have found obesity to be associated with an increased prevalence of asthma. For reasons that remain unclear, this association has often been reported to be stronger in women than in men. One possible explanation might be that these studies have used body mass index to identify adiposity, which might be a less reliable measure of body fat in men than in women. OBJECTIVE: We sought to explore the association between body fat percentage measured by means of bioelectrical impedance analysis and asthma, airflow obstruction, and airway inflammation in men and women. METHODS: Respiratory questionnaires, spirometry, bronchodilator response, exhaled nitric oxide level, and percentage of body fat were measured in a population-based cohort of approximately 1000 individuals at age 32 years. RESULTS: There was a significant association between the percentage of body fat and asthma in women (P = .043) but not in men (P = .75). Airflow obstruction was associated with percentage of body fat in women (P = .046), but there was an inverse association in men (P = .010). Bronchodilator responsiveness was also associated with lower body fat in men (P = .004). Airway inflammation, measured by means of exhaled nitric oxide, was not associated with body fat in either women (P = .17) or men (P = .25). CONCLUSION: Adiposity is associated with asthma and airflow obstruction in women. This does not appear to be mediated by airway inflammation. In men airflow obstruction and bronchodilator responsiveness are associated with a lower percentage of body fat. CLINICAL IMPLICATIONS: In women, but not in men, obesity is associated with asthma and airflow obstruction, but there was no association with airway inflammation.

Adipose Tissue↗

The impact of xerostomia on oral-health-related quality of life among younger adults.

BACKGROUND: Recent research has suggested that chronic dry mouth affects the day-to-day lives of older people living in institutions. The condition has usually been considered to be a feature of old age, but recent work by our team produced the somewhat surprising finding that 10% of people in their early thirties are affected. This raises the issue of whether dry mouth is a trivial condition or a more substantial threat to quality of life among younger people. The objective of this study was to examine the association between xerostomia and oral-health-related quality of life among young adults while controlling for clinical oral health status and other potential confounding factors. METHODS: Cross-sectional analysis of data from a longstanding prospective observational study of a Dunedin (New Zealand) birth cohort: clinical dental examinations and questionnaires were used at age 32. The main measures were xerostomia (the subjective feeling of dry mouth, measured with a single question) and oral-health-related quality of life (OHRQoL) measured using the short-form Oral Health Impact Profile (OHIP-14). RESULTS: Of the 923 participants (48.9% female), one in ten were categorised as 'xerostomic', with no apparent gender difference. There was a strong association between xerostomia and OHRQoL (across all OHIP-14 domains) which persisted after multivariate analysis to control for clinical characteristics, gender, smoking status and personality characteristics (negative emotionality and positive emotionality). CONCLUSION: Xerostomia is not a trivial condition; it appears to have marked and consistent effects on sufferers' day-to-day lives.

Adult↗

Early childhood factors associated with the development of post-traumatic stress disorder: results from a longitudinal birth cohort.

BACKGROUND: Childhood factors have been associated with increased risk of developing post-traumatic stress disorder (PTSD). Previous studies assessed only a limited number of childhood factors retrospectively. We examined the association between childhood neurodevelopmental, temperamental, behavioral and family environmental characteristics assessed before age 11 years and the development of PTSD up to age 32 years in a birth cohort. METHOD: Members of a 1972-73 New Zealand birth cohort (n=1037) who were assessed at ages 26 and 32 years for PTSD as defined by DSM-IV. RESULTS: We identified two sets of childhood risk factors. The first set of risk factors was associated both with increased risk of trauma exposure and with PTSD assessed at age 26. These included childhood externalizing characteristics and family environmental stressors, specifically maternal distress and loss of a parent. The second set of risk factors affected risk for PTSD only and included low IQ and chronic environmental adversity. The effect of cumulative childhood factors on risk of PTSD at age 26 was substantial; over 58% of cohort members in the highest risk quartile for three developmental factors had PTSD as compared to only 25% of those not at high risk on any factors. Low IQ at age 5, antisocial behavior, and poverty before age 11 continued to predict PTSD related to traumatic events that occurred between the ages of 26 and 32. CONCLUSIONS: Developmental capacities and conditions of early childhood may increase both risk of trauma exposure and the risk that individuals will respond adversely to traumatic exposures. Rather than being solely a response to trauma, PTSD may have developmental origins.

Adolescent↗

The Dunedin Multidisciplinary Health and Development Study: are its findings consistent with the overall New Zealand population?

AIMS: To compare the health of the Dunedin Multidisciplinary Health and Development Study members with people of the same age in the nationally representative New Zealand Health and National Nutrition Surveys. METHOD: Where similar information was obtained, means or proportions and confidence intervals were generated for both the age 26 assessment of the Dunedin sample and for the 25-26 year old participants in the national surveys. The populations were considered to differ when confidence intervals did not overlap. RESULTS: For smoking habit, body mass index, waist-hip ratio, general practitioner and medical specialist consultations, and hospital admissions, the findings of the Dunedin Study were not significantly different to the nationally representative surveys. The Dunedin Study members also did not differ from their national counterparts on SF-36 subscales measuring physical functioning, bodily pain, general health, vitality, and mental health. They had better scores on the three interference subscales of the SF-36 compared to the national sample, and men in the Dunedin Study spent a little more time doing vigorous physical activity. DISCUSSION: For most outcomes, the Dunedin Study members were very similar to the nationally representative samples. There was little evidence that the repeated assessments in the Dunedin Study had significantly altered the Study members' health, either in terms of responses to questionnaires or on physiological measures of health status. Findings from the Dunedin Study are likely to be generalisable to most young New Zealanders. However, the Dunedin Study is under-representative of Maori and Pacific peoples, so these findings need to be interpreted with caution in this context. Implications for the proposed national Longitudinal Study of New Zealand Children and Families are discussed.

Adult↗

Socially isolated children 20 years later: risk of cardiovascular disease.

OBJECTIVE: To test the hypothesis that children who occupy peripheral or isolated roles in their peer groups (isolated children) are at risk of poor adult health. DESIGN: Longitudinal study of an entire birth cohort. SETTING: Dunedin, New Zealand. PARTICIPANTS: A total of 1037 children who were followed up from birth to age 26 years. INTERVENTIONS: Measurement of social isolation in childhood, adolescence, and adulthood. MAIN OUTCOME MEASURES: When study members were 26 years old, we measured adult cardiovascular multifactorial risk status (overweight, elevated blood pressure, elevated total cholesterol level, low high-density lipoprotein level, elevated glycated hemoglobin concentration, and low maximum oxygen consumption). RESULTS: Socially isolated children were at significant risk of poor adult health compared with nonisolated children (risk ratio, 1.37; 95% confidence interval, 1.17-1.61). This association was independent of other well-established childhood risk factors for poor adult health (low childhood socioeconomic status, low childhood IQ, childhood overweight), was not accounted for by health-damaging behaviors (lack of exercise, smoking, alcohol misuse), and was not attributable to greater exposure to stressful life events. In addition, longitudinal findings showed that chronic social isolation across multiple developmental periods had a cumulative, dose-response relationship to poor adult health (risk ratio, 2.58; 95% confidence interval, 1.46-4.56). CONCLUSIONS: Longitudinal findings about children followed up to adulthood suggest that social isolation has persistent and cumulative detrimental effects on adult health. The findings underscore the usefulness of a life-course approach to health research, by focusing attention on the effect of the timing of psychosocial risk factors in relation to adult health.

Adolescent↗

Prediction of heterogeneity in intelligence and adult prognosis by genetic polymorphisms in the dopamine system among children with attention-deficit/hyperactivity disorder: evidence from 2 birth cohorts.

CONTEXT: The study and treatment of psychiatric disorders is made difficult by the fact that patients with identical symptoms often differ markedly in their clinical features and presumably in their etiology. A principal aim of genetic research is to provide new information that can resolve such clinical heterogeneity and that can be incorporated into diagnostic practice. OBJECTIVE: To test the hypothesis that the DRD4 seven-repeat allele and DAT1 ten-repeat allele would prove useful in identifying a subset of children with attention-deficit/hyperactivity disorder (ADHD) who have compromised intellectual functions. DESIGN: Longitudinal epidemiologic investigation of 2 independent birth cohorts. SETTING: Britain and New Zealand. PARTICIPANTS: The first cohort was born in Britain in 1994-1995 and includes 2232 children; the second cohort was born in New Zealand in 1972-1973 and includes 1037 children. MAIN OUTCOME MEASURES: Evaluation of ADHD, IQ, and adult psychosocial adjustment. RESULTS: We present replicated evidence that polymorphisms in the DRD4 and DAT1 genes were associated with variation in intellectual functioning among children diagnosed as having ADHD, apart from severity of their symptoms. We further show longitudinal evidence that these polymorphisms predicted which children with ADHD were at greatest risk for poor adult prognosis. CONCLUSION: The findings indicate that genetic information of this nature may prove useful for etiology-based psychiatric nosologies.

Adolescent↗

Low self-esteem during adolescence predicts poor health, criminal behavior, and limited economic prospects during adulthood.

Using prospective data from the Dunedin Multidisciplinary Health and Development Study birth cohort, the authors found that adolescents with low self-esteem had poorer mental and physical health, worse economic prospects, and higher levels of criminal behavior during adulthood, compared with adolescents with high self-esteem. The long-term consequences of self-esteem could not be explained by adolescent depression, gender, or socioeconomic status. Moreover, the findings held when the outcome variables were assessed using objective measures and informant reports; therefore, the findings cannot be explained by shared method variance in self-report data. The findings suggest that low self-esteem during adolescence predicts negative real-world consequences during adulthood.

Adolescent↗

Xerostomia and medications among 32-year-olds.

OBJECTIVE: To describe the prevalence and associations of xerostomia among adults in their early thirties, with particular attention to medication exposure as a putative risk factor. MATERIAL AND METHODS: The prevalence and associations of xerostomia were investigated among 32-year-old participants in a long-standing prospective cohort study. Some 950 individuals were assessed at ages 26 and 32 years, with medications being recorded on both occasions. RESULTS: The prevalence of xerostomia was 10.0% (with no apparent gender difference), and was significantly higher among those taking antidepressants (odds ratio = 4.7), iron supplements (OR = 4.1) or narcotic analgesics (OR = 2.4). Those taking antidepressants at both ages 26 and 32 years had 22 times the odds of reporting xerostomia. CONCLUSION: Xerostomia may be a problem for a sizeable minority of young adults.

Adult↗

Family conflict in childhood: a predictor of later insomnia.

STUDY OBJECTIVES: To examine the association between childhood exposure to family conflict and insomnia at 18 years of age. DESIGN: Longitudinal prospective data on an entire birth cohort were obtained. Parents completed the Conflict subscale of the Moos Family Environment Scale when the study members were 7, 9, 13, and 15 years of age. Insomnia was examined in a standardized interview when the participants were aged 18 years. SETTING: Participants were born in Dunedin, New Zealand, and were interviewed at this location. PATIENTS OR PARTICIPANTS: One thousand thirty-seven children born between April 1, 1972, and March 31, 1973, enrolled in the study (52% male). At age 18 years, 993 (97% of living cohort members) provided data. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: The mean level of family conflict at age 7 to 15 years predicted insomnia at 18 years after controlling for sex, socioeconomic status, sleep problems at 9 years, and self-reported health (odds ratio [95% confidence interval] = 1.42 [1.17-1.73], p < .001). There was a dose-response relationship, whereby the more assessments at which families scored in the top 25% for conflict, the greater the young person's likelihood of developing insomnia at age 18 years. This association was present even after controlling for depression at 18 years. CONCLUSIONS: This study demonstrates a modest but robust longitudinal link between family conflict during childhood and insomnia experienced at 18 years of age. Future work needs to replicate this finding in different populations and to elucidate the mechanisms underlying this association.

Adolescent↗

Neuropsychological performance at the age of 13 years and adult schizophreniform disorder: prospective birth cohort study.

We examined neuropsychological functioning at age 13 years in adolescents who later developed schizophreniform disorder, compared with healthy controls and with adolescents diagnosed as having had a manic episode or depression or anxiety disorder. Participants were from an unselected birth cohort. Attentional, executive and motor impairments at age 13 were found in those who later fulfilled diagnostic criteria for schizophreniform disorder, suggesting that these impairments may be the earliest emerging neuropsychological impairments in schizophrenia-related disorders.

Adolescent↗

Changes in periodontal disease experience from 26 to 32 years of age in a birth cohort.

BACKGROUND: Information is lacking on the natural history of periodontitis through the third and fourth decades of life. METHODS: Periodontal examinations were conducted at 26 and 32 years of age in a longstanding prospective study of a birth cohort born in Dunedin, New Zealand, in 1972 and 1973. At each age, gingival recession (GR) and probing depth (PD) were recorded at three sites per tooth using a diagonal half-mouth design (measurements were made in all four quadrants at 32 years of age, but longitudinal comparisons were made using only the half-mouth data). RESULTS: A total of 882 individuals were examined at both ages. The mean number of measured sites fell between 26 and 32 years of age. The overall prevalence of one or more sites with >or=4 mm combined attachment loss (CAL) rose from 18.6% to 21.8%, whereas there were greater increases in the proportion with two or more sites with >or=4 mm CAL (from 8.0% to 12.6%) and one or more sites with >or=5 mm CAL (from 3.6% to 8.0%). The extent and severity of CAL also increased. A total of 403 individuals (45.7%) had an increase in CAL >or=2 mm at one or more sites, whereas 110 (12.5%) had a CAL increase >or=3 mm at one or more sites. Seen in approximately 4% of sites, negative GR (i.e., gingival enlargement) had a substantial effect on PD-based estimates. An increase in PD >or=2 mm at one or more sites was experienced by 345 individuals (39.1%), whereas 88 people (10.0%) had an increase in PD >or=3 mm at one or more sites. The greatest mean attachment loss was experienced at disto-lingual sites on molars, and most manifested as PD increases. Notable increases in GR were seen with lower incisors and canines. CONCLUSIONS: Periodontal loss of attachment continues among a sizable proportion of people from the third to the fourth decade of life; however, contrary to patterns in older adults, changes in the PD component are greater than the changes in the recession component. Incident attachment loss is most frequently observed at proximal sites on posterior teeth.

Adult↗