Gene-environment correlation: the role of family environment in academic development.

Academic achievement is partly heritable and highly polygenic. However, genetic effects on academic achievement are not independent of environmental processes. We investigated whether aspects of the family environment mediated genetic effects on academic achievement across development. Our sample included 5151 children who participated in the Twins Early Development Study, as well as their parents and teachers. Data on academic achievement and family environments (parenting, home environments, and geocoded indices of neighbourhood characteristics) were available at ages 7, 9, 12 and 16. We computed educational attainment polygenic scores (PGS) and further separated genetic effects into cognitive and noncognitive PGS. Three core findings emerged. First, aspects of the family environment, but not the wider neighbourhood context, consistently mediated the PGS effects on achievement across development-accounting for up to 34.3% of the total effect. Family characteristics mattered beyond socio-economic status. Second, family environments were more robustly linked to noncognitive PGS effects on academic achievement than cognitive PGS effects. Third, when we investigated whether environmental mediation effects could also be observed when considering differences between siblings, adjusting for family fixed effects, we found that environmental mediation was nearly exclusively observed between families. This is consistent with the proposition that family environmental contexts contribute to academic development via passive gene-environment correlation processes or genetic nurture. Our results show how parents tend to shape environments that foster their children's academic development partly based on their own genetic disposition, particularly towards noncognitive skills, rather than responding to each child's genetic disposition.

Social isolation and poor mental health in young people: testing genetic and environmental influences in a longitudinal cohort study.

We assessed genetic and environmental influences on social isolation across childhood and the overlap between social isolation and mental health symptoms including depression symptoms, conduct problems, and psychotic-like experiences from adolescence to young adulthood. Participants included 2,232 children from the Environmental Risk Longitudinal Twin Study. Social isolation was measured at ages 5, 7, 10, 12, and 18. A Cholesky decomposition was specified to estimate the genetic and environmental influences on social isolation across ages 5, 7, 10, and 12. An independent pathway model was used to assess additive genetic (A), shared environmental (C), and non-shared environmental (E) influences on the overlap between social isolation and mental health problems from age 12 to 18. Genetic and non-shared environmental influences accounted for half of the variance in childhood social isolation. Genetic influences contributed to the continuity of social isolation across childhood, while non-shared environmental influences were age-specific. The longitudinal overlap between social isolation and mental health symptoms was largely explained by genetic influences for depression symptoms (r = 0.15-0.24: 82-84% A, 11-12% C, and 5-6% E) and psychotic-like experiences (r = 0.13-0.15: 81-91% A, 0-8% C, and 9-11% E) but not conduct problems (r = 0.13-0.16; 0-42% A, 42-81% C, 16-24% E). Our findings emphasise that rather than a risk factor or an outcome, social isolation is aetiologically intertwined with the experience of poor mental health. An integrative assessment of social isolation could be a helpful indicator of underlying mental health symptoms in young people.

The socioeconomic consequences of loneliness: Evidence from a nationally representative longitudinal study of young adults.

The negative health consequences of loneliness have led to increasing concern about the economic cost of loneliness in recent years. Loneliness may also incur an economic burden more directly, by impacting socioeconomic position. Much of the research to date has focused on employment status which may not fully capture socioeconomic position and has relied on cross-sectional data, leaving questions around the robustness of the association and reverse causation. The present study used longitudinal data to test prospective associations between loneliness and multiple indicators of social position in young adulthood, specifically, whether participants who were lonelier at age 12 were more likely to be out of employment, education and training (NEET) and lower on employability and subjective social status as young adults. The data were drawn from the Environmental Risk (E-Risk) Longitudinal Twin Study, a birth cohort of 2,232 individuals born in England and Wales during 1994-1995. Loneliness and subjective social status were measured at ages 12, 18 and 26. Employability and NEET status were assessed at age 18. Findings indicate that greater loneliness at age 12 was prospectively associated with reduced employability and lower social status in young adulthood. The association between loneliness and lower social status in young adulthood was robust when controlling for a range of confounders using a sibling-control design. Results also indicate that loneliness is unidirectionally associated with reduced subjective social status across adolescence and young adulthood. Overall, our findings suggest that loneliness may have direct costs to the economy resulting from reduced employability and social position, underlining the importance of addressing loneliness early in life.

Do polygenic indices capture "direct" effects on child externalizing behavior? Within-family analyses in two longitudinal birth cohorts.

Behaviors and disorders characterized by difficulties with self-regulation, such as problematic substance use, antisocial behavior, and symptoms of attention-deficit/hyperactivity disorder (ADHD), incur high costs for individuals, families, and communities. These externalizing behaviors often appear early in the life course and can have far-reaching consequences. Researchers have long been interested in direct measurements of genetic risk for externalizing behaviors, which can be incorporated alongside other known risk factors to improve efforts at early identification and intervention. In a preregistered analysis drawing on data from the Environmental Risk (E-Risk) Longitudinal Twin Study (N=862 twins) and the Millennium Cohort Study (MCS; N=2,824 parent-child trios), two longitudinal cohorts from the UK, we leveraged molecular genetic data and within-family designs to test for genetic effects on externalizing behavior that are unbiased by the common sources of environmental confounding. Results are consistent with the conclusion that an externalizing polygenic index (PGI) captures causal effects of genetic variants on externalizing problems in children and adolescents, with an effect size that is comparable to those observed for other established risk factors in the research literature on externalizing behavior. Additionally, we find that polygenic associations vary across development (peaking from age 5-10 years), that parental genetics (assortment and parent-specific effects) and family-level covariates affect prediction little, and that sex differences in polygenic prediction are present but only detectable using within-family comparisons. Based on these findings, we believe that the PGI for externalizing behavior is a promising means for studying the development of disruptive behaviors across child development.

Genetic associations with parental investment from conception to wealth inheritance in six cohorts.

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

Cross-National and Cross-Generational Evidence That Educational Attainment May Slow the Pace of Aging in European-Descent Individuals.

OBJECTIVES: Individuals with more education are at lower risk of developing multiple, different age-related diseases than their less-educated peers. A reason for this might be that individuals with more education age slower. There are 2 complications in testing this hypothesis. First, there exists no definitive measure of biological aging. Second, shared genetic factors contribute toward both lower educational attainment and the development of age-related diseases. Here, we tested whether the protective effect of educational attainment was associated with the pace of aging after accounting for genetic factors. METHODS: We examined data from 5 studies together totaling almost 17,000 individuals with European ancestry born in different countries during different historical periods, ranging in age from 16 to 98 years old. To assess the pace of aging, we used DunedinPACE, a DNA methylation algorithm that reflects an individual's rate of aging and predicts age-related decline and Alzheimer's disease and related disorders. To assess genetic factors related to education, we created a polygenic score based on the results of a genome-wide association study of educational attainment. RESULTS: Across the 5 studies, and across the life span, higher educational attainment was associated with a slower pace of aging even after accounting for genetic factors (meta-analysis effect size = -0.20; 95% confidence interval [CI]: -0.30 to -0.10; p = .006). Further, this effect persisted after taking into account tobacco smoking (meta-analysis effect size = -0.13; 95% CI: -0.21 to -0.05; p = .01). DISCUSSION: These results indicate that higher levels of education have positive effects on the pace of aging, and that the benefits can be realized irrespective of individuals' genetics.

Systematic review and meta-analysis of the effect of adverse childhood experiences (ACEs) on brain-derived neurotrophic factor (BDNF) levels.

There is continued interest in identifying dysregulated biomarkers that mediate associations between adverse childhood experiences (ACEs) and negative long-term health outcomes. However, little is known regarding how ACE exposure modulates neural biomarkers to influence poorer health outcomes in ACE-exposed children. To address this, we performed a systematic review and meta-analysis of the impact of ACE exposure on Brain Derived Neurotrophic Factor (BDNF) levels - a neural biomarker involved in childhood and adult neurogenesis and long-term memory formation. Twenty-two studies were selected for inclusion within the systematic review, ten of which were included in meta-analysis. Most included studies retrospectively assessed impacts of childhood maltreatment in clinical populations. Sample size, BDNF protein levels in ACE-exposed and unexposed subjects, and standard deviations were extracted from ten publications to estimate the BDNF ratio of means (ROM) across exposure categories. Overall, no significant difference was found in BDNF protein levels between ACE-exposed and unexposed groups (ROM: 1.08; 95 % CI: 0.93-1.26). Age at sampling, analyte type (e.g., sera, plasma, blood), and categories of ACE exposure contributed to high between-study heterogeneity, some of which was minimized in subset-based analyses. These results support continued investigation into the impact of ACE exposure on neural biomarkers and highlight the potential importance of analyte type and timing of sample collection on study results.

Something old, something new - can adding genomic data to family studies advance our understanding of the impact of nature and nurture on mental health? Commentary on McAdams et al. (2023).

In their annual research review, McAdams, Cheesman, and Ahmadzadeh (2023) provide a thorough overview of how the use of novel genetically informative approaches can increase our knowledge about the intergenerational transmission of psychopathology. Many JCPP readers will already be familiar with genetically sensitive family-based designs, such as twin and adoption studies, as well as with newer molecular-genetic approaches, such as polygenic-score studies. McAdams et al.'s (2023) review discusses the innovative combination of family-based and molecular-genetic methods, and what this combination can reveal about developmental psychopathology.

Childhood Adversity and Midlife Health: Shining a Light on the Black Box of Psychosocial Mechanisms.

Adverse childhood experiences (ACEs) are associated with poorer health, which has spurred public health efforts to reduce the number of adverse events children experience. Unfortunately, it is unlikely that all ACEs can be prevented. For adults who already experienced ACEs in childhood, what psychological, social, and behavioral intervention targets might reduce risk for negative health outcomes? To provide insight into the "black box" of psychosocial mechanisms linking ACEs to poor health, our study used data from the Dunedin Study, a longitudinal cohort assessed from birth to age 45. Mediation models (N = 859) were used to examine whether candidate psychosocial variables in adulthood explained the association between childhood ACEs and health in midlife. Potential psychosocial mediators included stressful life events, perceived stress, negative emotionality, and health behaviors. Children who experienced more ACEs had poorer health in midlife. They also had significantly more stressful life events, more perceived stress, more negative emotionality, and unhealthier behaviors as adults. These mediators were each independently associated with poorer health in midlife and statistically mediated the association between ACEs and midlife health. Health behaviors evidenced the strongest indirect effect from ACEs to midlife health. Together, these psychosocial mediators accounted for the association between ACEs in childhood and health three decades later. Public health efforts to mitigate the health consequences of ACEs could aim to reduce the stressful life events people experience, reduce negative emotionality, reduce perceived stress, or improve health behaviors among adults who experienced childhood adversity.

The effect of online social evaluation on mood and cognition in young people.

Adolescence is characterised by increased peer interactions and heightened sensitivity to evaluation by peers. Increasingly, social interactions and evaluation happen in online contexts. Yet, little is known about the impact of online social interactions and evaluation on adolescent emotional and cognitive functioning. The present study examined the impact of online social evaluative threat on young people's mood and learning and whether this varied as a function of known offline social risk and protective factors. 255 participants completed a perceptual learning task under online social evaluative threat and a perceptually-matched control condition. Participants were aged 11-30 years, to allow for the exploration of age differences in the impact of online social evaluative threat from adolescence to early adulthood. Participants reported a greater increase in negative mood (self-reported levels of stress, anxiety, and anhedonia), following social evaluative threat compared to the control condition. Heightened social rejection sensitivity (measured using the Online and Offline Social Sensitivity Scale) and lower perceived social support (measured using the Schuster Social Support Scale) were associated with elevated negative mood across the study. Social evaluative threat adversely impacted overall accuracy on the perceptual matching task, but not learning. These findings provide preliminary evidence that online social evaluative threat impacts adolescent mood and cognitive functioning.

Mother's and children's ADHD genetic risk, household chaos and children's ADHD symptoms: A gene-environment correlation study.

BACKGROUND: Chaotic home environments may contribute to children's attention-deficit hyperactivity disorder (ADHD) symptoms. However, ADHD genetic risk may also influence household chaos. This study investigated whether children in chaotic households had more ADHD symptoms, if mothers and children with higher ADHD genetic risk lived in more chaotic households, and the joint association of genetic risk and household chaos on the longitudinal course of ADHD symptoms across childhood. METHODS: Participants were mothers and children from the Environmental Risk (E-Risk) Longitudinal Twin Study, a UK population-representative birth cohort of 2,232 twins. Children's ADHD symptoms were assessed at ages 5, 7, 10 and 12 years. Household chaos was rated by research workers at ages 7, 10 and 12, and by mother's and twin's self-report at age 12. Genome-wide ADHD polygenic risk scores (PRS) were calculated for mothers (n = 880) and twins (n = 1,999); of these, n = 871 mothers and n = 1,925 children had information on children's ADHD and household chaos. RESULTS: Children in more chaotic households had higher ADHD symptoms. Mothers and children with higher ADHD PRS lived in more chaotic households. Children's ADHD PRS was associated with household chaos over and above mother's PRS, suggesting evocative gene-environment correlation. Children in more chaotic households had higher baseline ADHD symptoms and a slower rate of decline in symptoms. However, sensitivity analyses estimated that gene-environment correlation accounted for a large proportion of the association of household chaos on ADHD symptoms. CONCLUSIONS: Children's ADHD genetic risk was independently associated with higher levels of household chaos, emphasising the active role of children in shaping their home environment. Our findings suggest that household chaos partly reflects children's genetic risk for ADHD, calling into question whether household chaos directly influences children's core ADHD symptoms. Our findings highlight the importance of considering parent and child genetic risk in relation to apparent environmental exposures.

Gene-environment interplay in externalizing behavior from childhood through adulthood.

BACKGROUND: Genetic and environmental influences on externalizing problems are often studied separately. Here, we extended prior work by investigating the implications of gene-environment interplay in childhood for early adult externalizing behavior. Genetic nurture would be indicated if parents' genetic predisposition for externalizing behavior operates through the family environment in predicting offspring early adult externalizing behavior. Evocative gene-environment correlation would be indicated if offspring genetic predisposition for externalizing behavior operates through child externalizing behavior in affecting the family environment and later early adult externalizing behavior. METHOD: Longitudinal data from seven waves of the TRacking Adolescents' Individual Lives Survey, a prospective cohort study of Dutch adolescents followed from age 11 to age 29 (n at baseline = 2,734) were used. Child externalizing behavior was assessed using self and parent reports. Family dysfunction was assessed by parents. Early adult externalizing behavior was assessed using self-reports. Genome-wide polygenic scores for externalizing problems were constructed for mothers, fathers, and offspring. RESULTS: Offspring polygenic score and child behavior each predicted early adult externalizing problems, as did family dysfunction to a small extent. Parents' polygenic scores were not associated with offspring's early adult externalizing behavior. Indirect effect tests indicated that offspring polygenic score was associated with greater family dysfunction via child externalizing behavior (evocative gene-environment correlation) but the effect was just significant and the effect size was very small. Parents' polygenic scores did not predict family dysfunction, thus the data do not provide support for genetic nurture. CONCLUSIONS: A very small evocative gene-environment correlation was detected but effect sizes were much more pronounced for stability in externalizing behavior from childhood through early adulthood, which highlights the necessity to intervene early to prevent later problems.

Vital personality scores and healthy aging: Life-course associations and familial transmission.

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.

Autistic traits are associated with faster pace of aging: Evidence from the Dunedin study at age 45.

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 (ß = 0.09), facial age (ß = 0.08), self- (ß = -0.15), informant (ß = -0.12), and interviewer-rated (ß = -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.

Bullying behaviours and other conduct problems: longitudinal investigation of their independent associations with risk factors and later outcomes.

PURPOSE: Bullying behaviours and other conduct problems often co-occur. However, we do not yet know whether bullying behaviours are associated with early factors and later poor outcomes independently of conduct problems. While there are differing, specific interventions for bullying behaviours and for conduct problems, it is unclear if such specificity is justified given parallels between both behaviours. METHODS: We used prospective data from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative sample of 2232 children. Mothers and teachers reported on children's bullying behaviours and conduct problems at ages 7 and 10. We collected measures of risk factors, including temperament and family factors, when children were age 5. We assessed behavioural, emotional, educational and social problems when participants reached the ages of 12 and 18. RESULTS: Bullying behaviours and conduct problems co-occurred in childhood. Our findings indicated that bullying behaviours and other conduct problems were independently associated with the same risk factors. Furthermore, they were associated with the same poor outcomes at both ages 12 and 18. Despite this, bullying behaviours were uniquely associated with behavioural, emotional, educational and social problems at age 18. CONCLUSIONS: Our findings suggest that anti-bullying programmes and interventions aimed at reducing conduct problems could benefit from greater integration. Furthermore, our study highlights the mental health problems children who bully may face in later years and the need to consider those in intervention plans.

Association of History of Psychopathology With Accelerated Aging at Midlife.

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 (ß, 0.27; 95% CI, 0.21-0.33; P < .01); experienced more difficulties with hearing (ß, 0.18; 95% CI, 0.12-0.24; P < .01), vision (ß, 0.08; 95% CI, 0.01-0.14; P < .05), balance (ß, 0.20; 95% CI, 0.14-0.26; P < .01), and motor functioning (ß, 0.19; 95% CI, 0.12-0.25; P < .01); experienced more cognitive difficulties (ß, 0.24; 95% CI, 0.18-0.31; P < .01); and were rated as looking older (ß, 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.

Investigating the genetic architecture of noncognitive skills using GWAS-by-subtraction.

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.

Polygenic Risk and the Course of Attention-Deficit/Hyperactivity Disorder From Childhood to Young Adulthood: Findings From a Nationally Representative Cohort.

OBJECTIVE: To understand whether genetic risk for attention-deficit/hyperactivity disorder (ADHD) is associated with the course of the disorder across childhood and into young adulthood. METHOD: Participants were from the Environmental Risk (E-Risk) Longitudinal Twin Study, a population-based birth cohort of 2,232 twins. ADHD was assessed at ages 5, 7, 10, and 12 with mother- and teacher-reports and at age 18 with self-report. Polygenic risk scores (PRSs) were created using a genome-wide association study of ADHD case status. Associations with PRS were examined at multiple points in childhood and longitudinally from early childhood to adolescence. We investigated ADHD PRS and course to young adulthood, as reflected by ADHD remission, persistence, and late onset. RESULTS: Participants with higher ADHD PRSs had increased risk for meeting ADHD diagnostic criteria (odds ratios ranging from 1.17 at age 10 to 1.54 at age 12) and for elevated symptoms at ages 5, 7, 10, and 12. Higher PRS was longitudinally associated with more hyperactivity/impulsivity (incidence rate ratio = 1.18) and inattention (incidence rate ratio = 1.14) from age 5 to age 12. In young adulthood, participants with persistent ADHD exhibited the highest PRS (mean PRS = 0.37), followed by participants with remission (mean PRS = 0.21); both groups had higher PRS than controls (mean PRS = -0.03), but did not significantly differ from one another. Participants with late-onset ADHD did not show elevated PRS for ADHD, depression, alcohol dependence, or marijuana use disorder. CONCLUSION: Genetic risk scores derived from case-control genome-wide association studies may have relevance not only for incidence of mental health disorders, but also for understanding the longitudinal course of mental health disorders.

Childhood self-control forecasts the pace of midlife aging and preparedness for old age.

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.