The causal effect of mental health on labor market outcomes: The case of stress-related mental disorders following a human-made disaster.

As disasters increase due to climate change, population density, epidemics, and technology, information is needed about postdisaster consequences for people's mental health and how stress-related mental disorders affect multiple spheres of life, including labor-market attachment. We tested the causal hypothesis that individuals who developed stress-related mental disorders as a consequence of their disaster exposure experienced subsequent weak labor-market attachment and poor work-related outcomes. We leveraged a natural experiment in an instrumental variables model, studying a 2004 fireworks factory explosion disaster that precipitated the onset of stress-related disorders (posttraumatic stress disorder, anxiety, and depression) among individuals in the local community (N = 86,726). We measured labor-market outcomes using longitudinal population-level administrative data: sick leave, unemployment benefits, early retirement pension, and income from wages from 2007 to 2010. We found that individuals who developed a stress-related disorder after the disaster were likely to go on sickness benefit, both in the short- and long-term, were likely to use unemployment benefits and to lose wage income in the long term. Stress-related disorders did not increase the likelihood of early retirement. The natural experiment design minimized the possibility that omitted confounders biased these effects of mental health on work outcomes. Addressing the mental health and employment needs of survivors after a traumatic experience may improve their labor-market outcomes and their nations' economic outputs.

Midlife diseases of despair and cardiometabolic risk: testing shared origins in adolescent psychopathology.

BACKGROUND: Rising midlife mortality in the United States is largely attributable to 'deaths of despair' (deaths from suicide, drug poisonings, and alcohol-related diseases) and deaths from cardiometabolic conditions. Although despair- and cardiometabolic-related mortality are increasing concurrently, it is unclear whether they share common developmental origins. We tested adolescent psychopathology as a potential common origin of midlife diseases of despair and cardiometabolic risk. METHODS: Participants (N = 4578) were from the National Longitudinal Study of Adolescent to Adult Health, a nationally representative cohort followed from adolescence to early midlife. Adolescent psychopathology included depression, anxiety, eating disorders, PTSD, conduct disorder, and ADHD at ages 11-18. Diseases of despair (suicidality, substance misuse, pain, and sleep problems) and cardiometabolic risk (hypertension, hyperlipidemia, high-risk waist circumference, diabetes, and cardiovascular conditions) were multi-modally measured at ages 33-43. RESULTS: At midlife, adolescents who experienced psychopathology exhibited more indicators of despair-related diseases and cardiometabolic risk (IRRs = 1.67 [1.46-1.87] and 1.13 [1.04-1.21], respectively), even after accounting for demographics, adolescent SES, and adolescent cognitive ability. Associations were evident for internalizing and externalizing conditions, and in a dose-response fashion. In mediation analyses, low education explained little of these associations, but early-adult substance use explained 21.5% of psychopathology's association with despair-related diseases. Midlife despair-related diseases and cardiometabolic risk co-occurred within individuals (IRR = 1.12 [1.08-1.16]). Adolescent psychopathology accounted for 8.3% of this co-occurrence, and 16.7% together with adolescent SES and cognitive ability. CONCLUSIONS: Adolescent psychopathology precedes both diseases of despair and cardiometabolic risk. Prevention and treatment of psychopathology may mitigate multiple causes of poor midlife health, reducing premature mortality.

Suicides, drug poisonings, and alcohol-related deaths cluster with health and social disadvantage in 4.1 million citizens from two nations.

BACKGROUND: Deaths from suicides, drug poisonings, and alcohol-related diseases ('deaths of despair') are well-documented among working-age Americans, and have been hypothesized to be largely specific to the U.S. However, support for this assertion-and associated policies to reduce premature mortality-requires tests concerning these deaths in other industrialized countries, with different institutional contexts. We tested whether the concentration and accumulation of health and social disadvantage forecasts deaths of despair, in New Zealand and Denmark. METHODS: We used nationwide administrative data. Our observation period was 10 years (NZ = July 2006-June 2016, Denmark = January 2007-December 2016). We identified all NZ-born and Danish-born individuals aged 25-64 in the last observation year (NZ = 1 555 902, Denmark = 2 541 758). We ascertained measures of disadvantage (public-hospital stays for physical- and mental-health difficulties, social-welfare benefit-use, and criminal convictions) across the first nine years. We ascertained deaths from suicide, drugs, alcohol, and all other causes in the last year. RESULTS: Deaths of despair clustered within a population segment that disproportionately experienced multiple disadvantages. In both countries, individuals in the top 5% of the population in multiple health- and social-service sectors were at elevated risk for deaths from suicide, drugs, and alcohol, and deaths from other causes. Associations were evident across sex and age. CONCLUSIONS: Deaths of despair are a marker of inequalities in countries beyond the U.S. with robust social-safety nets, nationwide healthcare, and strong pharmaceutical regulations. These deaths cluster within a highly disadvantaged population segment identifiable within health- and social-service systems.

Nationwide evidence that education disrupts the intergenerational transmission of disadvantage.

Despite overall improvements in health and living standards in the Western world, health and social disadvantages persist across generations. Using nationwide administrative databases linked for 2.1 million Danish citizens, we leveraged a three-generation approach to test whether multiple, different health and social disadvantages-poor physical health, poor mental health, social welfare dependency, criminal offending, and Child Protective Services involvement-were transmitted within families and whether education disrupted these statistical associations. Health and social disadvantages concentrated, aggregated, and accumulated within a small, high-need segment of families: Adults who relied disproportionately on multiple, different health and social services tended to have parents who relied disproportionately on multiple, different health and social services and tended to have children who evidenced risk for disadvantage at an early age, through appearance in protective services records. Intra- and intergenerational comparisons were consistent with the possibility that education disrupted this transmission. Within families, siblings who obtained more education were at a reduced risk for later-life disadvantage compared with their cosiblings who obtained less education, despite shared family background. Supporting the education potential of the most vulnerable citizens might mitigate the multigenerational transmission of multiple disadvantages and reduce health and social disparities.

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.

Dementia, dementia's risk factors and premorbid brain structure are concentrated in disadvantaged areas: National register and birth-cohort geographic analyses.

INTRODUCTION: Dementia risk may be elevated in socioeconomically disadvantaged neighborhoods. Reasons for this remain unclear, and this elevation has yet to be shown at a national population level. METHODS: We tested whether dementia was more prevalent in disadvantaged neighborhoods across the New Zealand population (N = 1.41 million analytic sample) over a 20-year observation. We then tested whether premorbid dementia risk factors and MRI-measured brain-structure antecedents were more prevalent among midlife residents of disadvantaged neighborhoods in a population-representative NZ-birth-cohort (N = 938 analytic sample). RESULTS: People residing in disadvantaged neighborhoods were at greater risk of dementia (HR per-quintile-disadvantage-increase = 1.09, 95% confidence interval [CI]:1.08-1.10) and, decades before clinical endpoints typically emerge, evidenced elevated dementia-risk scores (CAIDE, LIBRA, Lancet, ANU-ADRI, DunedinARB; ß's 0.31-0.39) and displayed dementia-associated brain structural deficits and cognitive difficulties/decline. DISCUSSION: Disadvantaged neighborhoods have more residents with dementia, and decades before dementia is diagnosed, residents have more dementia-risk factors and brain-structure antecedents. Whether or not neighborhoods causally influence risk, they may offer scalable opportunities for primary dementia prevention.

Disordered gambling in a longitudinal birth cohort: from childhood precursors to adult life outcomes.

BACKGROUND: Despite its introduction into the diagnostic nomenclature over four decades ago, there remain large knowledge gaps about disordered gambling. The primary aims of the present study were to document the long-term course, childhood precursors, and adult life outcomes associated with disordered gambling. METHODS: Participants enrolled in the population-representative Dunedin Study were prospectively followed from birth through age 45. Disordered gambling was assessed six times from age 18; composite measures of childhood social class, general intelligence, and low self-control were based on assessments obtained from birth through age 15; adult socioeconomic, financial, and legal outcomes were obtained through age 45. Lifetime disordered gambling was predicted from the three childhood precursors and the adult outcomes were predicted from lifetime disordered gambling. RESULTS: Past-year disordered gambling usually occurred at only a single time point and recurrence was relatively uncommon. Lower childhood social class, general intelligence, and self-control significantly predicted lifetime disordered gambling in adulthood. In turn, lifetime disordered gambling in adulthood significantly predicted occupational, educational, and financial problems in adulthood (ds = 0.23-0.41). These associations were markedly reduced and sometimes rendered nonsignificant after adjusting for childhood precursors (ds = 0.04-0.32). CONCLUSIONS: Socioeconomic, financial, and legal outcomes in adulthood are not merely consequences of disordered gambling, but also are predicted from childhood precursors. Deflecting the trajectories of young people at risk for developing disordered gambling may help to ameliorate not just the development of later disordered gambling, but also other associated adverse outcomes.

A polygenic score for age-at-first-birth predicts disinhibition.

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

Using DNA From Mothers and Children to Study Parental Investment in Children's Educational Attainment.

This study tested implications of new genetic discoveries for understanding the association between parental investment and children's educational attainment. A novel design matched genetic data from 860 British mothers and their children with home-visit measures of parenting: the E-Risk Study. Three findings emerged. First, both mothers' and children's education-associated genetics, summarized in a genome-wide polygenic score, were associated with parenting-a gene-environment correlation. Second, accounting for genetic influences slightly reduced associations between parenting and children's attainment-indicating some genetic confounding. Third, mothers' genetics were associated with children's attainment over and above children's own genetics, via cognitively stimulating parenting-an environmentally mediated effect. Findings imply that, when interpreting parents' effects on children, environmentalists must consider genetic transmission, but geneticists must also consider environmental transmission.

Common genetic contributions to high-risk trauma exposure and self-injurious thoughts and behaviors.

BACKGROUND: Prior research has documented shared heritable contributions to non-suicidal self-injury (NSSI) and suicidal ideation (SI) as well as NSSI and suicide attempt (SA). In addition, trauma exposure has been implicated in risk for NSSI and suicide. Genetically informative studies are needed to determine common sources of liability to all three self-injurious thoughts and behaviors, and to clarify the nature of their associations with traumatic experiences. METHODS: Multivariate biometric modeling was conducted using data from 9526 twins [59% female, mean age = 31.7 years (range 24-42)] from two cohorts of the Australian Twin Registry, some of whom also participated in the Childhood Trauma Study and the Nicotine Addiction Genetics Project. RESULTS: The prevalences of high-risk trauma exposure (HRT), NSSI, SI, and SA were 24.4, 5.6, 27.1, and 4.6%, respectively. All phenotypes were moderately to highly correlated. Genetic influences on self-injurious thoughts and behaviors and HRT were significant and highly correlated among men [rG = 0.59, 95% confidence interval (CI) (0.37-0.81)] and women [rG = 0.56 (0.49-0.63)]. Unique environmental influences were modestly correlated in women [rE = 0.23 (0.01-0.45)], suggesting that high-risk trauma may confer some direct risk for self-injurious thoughts and behaviors among females. CONCLUSIONS: Individuals engaging in NSSI are at increased risk for suicide, and common heritable factors contribute to these associations. Preventing trauma exposure may help to mitigate risk for self-harm and suicide, either directly or indirectly via reductions in liability to psychopathology more broadly. In addition, targeting pre-existing vulnerability factors could significantly reduce risk for life-threatening behaviors among those who have experienced trauma.

A Novel Tobacco Use Phenotype Suggests the 15q25 and 19q13 Loci May be Differentially Associated With Cigarettes per Day and Tobacco-Related Problems.

INTRODUCTION: Tobacco use is associated with variation at the 15q25 gene cluster and the cytochrome P450 (CYP) genes CYP2A6 and CYP2B6. Despite the variety of outcomes associated with these genes, few studies have adopted a data-driven approach to defining tobacco use phenotypes for genetic association analyses. We used factor analysis to generate a tobacco use measure, explored its incremental validity over a simple indicator of tobacco involvement: cigarettes per day (CPD), and tested both phenotypes in a genetic association study. METHODS: Data were from the University of California, San Francisco Family Alcoholism Study (n = 1942) and a Native American sample (n = 255). Factor analyses employed a broad array of tobacco use variables to establish the candidate phenotype. Subsequently, we conducted tests for association with variants in the nicotinic acetylcholine receptor and CYP genes. We explored associations with CPD and our measure. We then examined whether the variants most strongly associated with our measure remained associated after controlling for CPD. RESULTS: Analyses identified one factor that captured tobacco-related problems. Variants at 15q25 were significantly associated with CPD after multiple testing correction (rs938682: p = .00002, rs1051730: p = .0003, rs16969968: p = .0003). No significant associations were obtained with the tobacco use phenotype; however, suggestive associations were observed for variants in CYP2B6 near CYP2A6 (rs45482602: ps = .0082, .0075) and CYP4Z2P (rs10749865: ps = .0098, .0079). CONCLUSIONS: CPD captures variation at 15q25. Although strong conclusions cannot be drawn, these finding suggest measuring additional dimensions of problems may detect genetic variation not accounted for by smoking quantity. Replication in independent samples will help further refine phenotype definition efforts. IMPLICATIONS: Different facets of tobacco-related problems may index unique genetic risk. CPD, a simple measure of tobacco consumption, is associated with variants at the 15q25 gene cluster. Additional dimensions of tobacco problems may help to capture variation at 19q13. Results demonstrate the utility of adopting a data-driven approach to defining phenotypes for genetic association studies of tobacco involvement and provide results that can inform replication efforts.

Peer connectedness and substance use in adolescence: A systematic review and meta-analysis.

OBJECTIVE: Adolescents' relationships with their peers play a pivotal role in their substance-use behaviors. As such, decades of research have examined how substance use relates to adolescents' overall levels of closeness to their peers, here termed peer connectedness, with mixed results. This report sought to determine how the operationalizations of peer connectedness and substance use affect the nature of the relationship between them. METHOD: We used a systematic review strategy to find a comprehensive set of studies investigating the relationship between peer connectedness and substance use. Three-level meta-analytic regression was used to empirically test whether the operationalization of these variables moderates effect sizes across studies. RESULTS: We found 147 studies, of which 128 were analyzed using multilevel meta-analytic regression models. Operationalizations of peer connectedness varied widely, encompassing sociometric and self-report measures. Of these measures, sociometric indices specifically pertaining to popularity were most strongly predictive of substance use. Less consistent relationships were observed between substance use and sociometric measures of friendship, as well as with self-report measures. CONCLUSIONS: Being perceived as popular by one's peers is positively related to substance use among adolescents. This relationship is stronger and more consistent than those between substance use and other peer-connectedness variables, underscoring the necessity of operationalizing these constructs specifically and clearly. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Associations of hospital-treated infections with subsequent dementia: nationwide 30-year analysis.

Infections, which can prompt neuroinflammation, may be a risk factor for dementia1-5. More information is needed concerning associations across different infections and different dementias, and from longitudinal studies with long follow-ups. This New Zealand-based population register study tested whether infections antedate dementia across three decades. We identified individuals born between 1929 and 1968 and followed them from 1989 to 2019 (n = 1,742,406, baseline age = 21-60 years). Infection diagnoses were ascertained from public hospital records. Dementia diagnoses were ascertained from public hospital, mortality and pharmaceutical records. Relative to individuals without an infection, those with an infection were at increased risk of dementia (hazard ratio 2.93, 95% confidence interval 2.68-3.20). Associations were evident for dementia diagnoses made up to 25-30 years after infection diagnoses. Associations held after accounting for preexisting physical diseases, mental disorders and socioeconomic deprivation. Associations were evident for viral, bacterial, parasitic and other infections, and for Alzheimer's disease and other dementias, including vascular dementia. Preventing infections might reduce the burden of neurodegenerative conditions.

Exposure to community violence as a mechanism linking neighborhood socioeconomic disadvantage and neural responses to reward.

A growing literature links socioeconomic disadvantage and adversity to brain function, including disruptions in reward processing. Less research has examined exposure to community violence (ECV) as a specific adversity related to differences in reward-related brain activation, despite the prevalence of community violence exposure for those living in disadvantaged contexts. The current study tested whether ECV was associated with reward-related ventral striatum (VS) activation after accounting for familial factors associated with differences in reward-related activation (e.g. parenting and family income). Moreover, we tested whether ECV is a mechanism linking socioeconomic disadvantage to reward-related activation in the VS. We utilized data from 444 adolescent twins sampled from birth records and residing in neighborhoods with above-average levels of poverty. ECV was associated with greater reward-related VS activation, and the association remained after accounting for family-level markers of disadvantage. We identified an indirect pathway in which socioeconomic disadvantage predicted greater reward-related activation via greater ECV, over and above family-level adversity. These findings highlight the unique impact of community violence exposure on reward processing and provide a mechanism through which socioeconomic disadvantage may shape brain function.

Investigating the influence of prenatal androgen exposure and sibling effects on alcohol use and alcohol use disorder in females from opposite-sex twin pairs.

BACKGROUND: There are robust sex differences for alcohol phenotypes, with men reporting more drinking and alcohol use disorder (AUD) symptoms than women. However, the sources of these effects are not completely understood. Sex hormones, a substantial biological sex difference, exert neurobehavioral influences and are candidates for influencing sex differences in alcohol phenotypes. This study investigated the effects of prenatal androgens based on the hypothesis of prenatal hormone transfer, which posits that hormones from one twin influence the development of a cotwin. METHODS: This study compared female twins from opposite-sex (OSF) and same-sex (SSF) pairs to investigate associations between prenatal androgens and alcohol phenotypes. Additional analyses distinguished prenatal and postnatal effects by comparing OSFs and SSFs with a close-in-age older (CAO) brother. RESULTS: OSFs endorsed more lifetime AUD symptoms than SSFs (d = 0.14). Females with a CAO brother reported greater intoxication frequency (d = 0.35), hangover frequency (d = 0.24), typical drinking quantity (d = 0.33), and max drinks (i.e., the most drinks ever consumed in a 24-hour period; d = 0.29). Controlling for postnatal effects, OSFs still endorsed more lifetime AUD symptoms than SSFs with a CAO brother (d = 0.16). CONCLUSIONS: Prenatal exposure to a male cotwin was associated with increases in AUD symptoms, above the effect of postnatal exposure to a male sibling. Prenatal exposure to a male cotwin was not associated with increases in other alcohol-related phenotypes, but postnatal exposure to older male siblings produced medium effect sizes for indicators of alcohol consumption. Sex differences in AUDs, but not alcohol use, may be partially due to the neurodevelopmental effects of prenatal androgens. However, sibling effects may be larger than any effect of prenatal androgen exposure.

Effects of sibship size and composition on younger brothers' and sisters' alcohol use initiation: findings from an Australian twin sample.

BACKGROUND: The effects of sibship size and structure on delinquency are well established. Specifically, having a large family and many brothers has been shown to predict offending. However, despite strong links between delinquency and alcohol use, the contribution of sibship factors to drinking behaviors remains largely unexplored. The current study investigated the impact of sibship size and composition on younger brothers' and sisters' ages of drinking and intoxication onset. METHODS: We employed a sample of 4,281 same-sex twins from the Australian Twin Register to examine whether (i) large sibship size facilitates earlier age at first drink (AFD) and age at first intoxication (AFI) in males and females, (ii) having many older brothers predicts earlier ages of AFD and AFI in males, and (iii) having many older brothers results in later AFD and AFI in females. We tested whether effects were moderated by parental divorce and alcohol misuse and mediated by familial religion. RESULTS: Sibling effects were minimal before accounting for family context. However, when parental divorce and excessive parental drinking were included as moderators, sibling effects were significantly amplified among individuals from homes of divorce, and effects were strongest when siblings were close in age. CONCLUSIONS: Strong close in age older sibling effects indicate that proximal sibling attitudes and behaviors about alcohol likely interact with structural factors to influence younger siblings' drinking. Sibship factors were much more influential in one population (individuals from homes of divorce) than another (respondents with a parental history of excessive drinking), suggesting that sibling effects vary depending on the type of co-occurring familial risk. Prevention efforts performed at the family level, and introduced before first use of alcohol, are likely to delay drinking initiation and help prevent future alcohol problems.

Shared genetic vulnerability for disordered gambling and alcohol use disorder in men and women: evidence from a national community-based Australian Twin Study.

Disordered gambling (DG) will soon be included along with the substance use disorders in a revised diagnostic category of the Diagnostic and Statistical Manual of Mental Disorders DSM-5 called 'Substance Use and Addictive Disorders'. This was premised in part on the common etiologies of DG and the substance use disorders. Using data from the national community-based Australian Twin Registry, we used biometric model fitting to examine the extent to which the genetic liabilities for DG and alcohol use disorder (AUD) were shared, and whether this differed for men and women. The effect of using categorical versus dimensional DG and AUD phenotypes was explored, as was the effect of using diagnoses based on the DSM-IV and the proposed DSM-5 diagnostic criteria. The genetic correlations between DG and AUD ranged from 0.29 to 0.44. There was a significantly larger genetic correlation between DG and AUD among men than women when using dimensional phenotypes. Overall, about one-half to two-thirds of the association between DG and AUD was due to a shared genetic vulnerability. This study represents one of the few empirical demonstrations of an overlap in the genetic risk for DG and another substance-related addictive disorder. More research is needed on the genetic overlap between DG and other substance use disorders, as well as the genetic overlap between DG and other (non-substance-related) psychiatric disorders.

Longitudinal Associations of Mental Disorders With Dementia: 30-Year Analysis of 1.7 Million New Zealand Citizens.

IMPORTANCE: Mental disorders are an underappreciated category of modifiable risk factors for dementia. Developing an evidence base about the link between mental disorders and dementia risk requires studies that use large, representative samples, consider the full range of psychiatric conditions, ascertain mental disorders from early life, use long follow-ups, and distinguish between Alzheimer disease and related dementias. OBJECTIVE: To test whether mental disorders antedate dementia across 3 decades of observation. DESIGN, SETTING, AND PARTICIPANTS: This population-based administrative register study of mental disorders and Alzheimer disease and related dementias included all individuals born in New Zealand between 1928 and 1967 who resided in the country for any time during the 30-year observation period between July 1988 and June 2018. Data were from the New Zealand Integrated Data Infrastructure, a collection of whole-of-population administrative data sources linked at the individual level. Data were analyzed from October 2020 to November 2021. EXPOSURES: Diagnoses of mental disorders were ascertained from public-hospital records. MAIN OUTCOMES AND MEASURES: Diagnoses of dementia were ascertained from public-hospital records, mortality records, and pharmaceutical records. RESULTS: Of 1 711 386 included individuals, 866 301 (50.6%) were male, and individuals were aged 21 to 60 years at baseline. Relative to individuals without a mental disorder, those with a mental disorder were at increased risk of developing subsequent dementia (relative risk [RR], 4.24; 95% CI, 4.07-4.42; hazard ratio, 6.49; 95% CI, 6.25-6.73). Among individuals with dementia, those with a mental disorder developed dementia a mean of 5.60 years (95% CI, 5.31-5.90) earlier than those without a mental disorder. Associations held across sex and age and after accounting for preexisting chronic physical diseases and socioeconomic deprivation. Associations were present across different types of mental disorders and self-harm behavior (RRs ranged from 2.93 [95% CI, 2.66-3.21] for neurotic disorders to 6.20 [95% CI, 5.67-6.78] for psychotic disorders), and were evident for Alzheimer disease (RR, 2.76; 95% CI, 2.45-3.11) and all other dementias (RR, 5.85; 95% CI, 5.58-6.13). CONCLUSIONS AND RELEVANCE: In this study, mental disorders were associated with the onset of dementia in the population. Ameliorating mental disorders in early life might also ameliorate neurodegenerative conditions and extend quality of life in old age.

Polygenic Liability to Depression Is Associated With Multiple Medical Conditions in the Electronic Health Record: Phenome-wide Association Study of 46,782 Individuals.

BACKGROUND: Major depressive disorder (MDD) is a leading cause of disease-associated disability, with much of the increased burden due to psychiatric and medical comorbidity. This comorbidity partly reflects common genetic influences across conditions. Integrating molecular-genetic tools with health records enables tests of association with the broad range of physiological and clinical phenotypes. However, standard phenome-wide association studies analyze associations with individual genetic variants. For polygenic traits such as MDD, aggregate measures of genetic risk may yield greater insight into associations across the clinical phenome. METHODS: We tested for associations between a genome-wide polygenic risk score for MDD and medical and psychiatric traits in a phenome-wide association study of 46,782 unrelated, European-ancestry participants from the Michigan Genomics Initiative. RESULTS: The MDD polygenic risk score was associated with 211 traits from 15 medical and psychiatric disease categories at the phenome-wide significance threshold. After excluding patients with depression, continued associations were observed with respiratory, digestive, neurological, and genitourinary conditions; neoplasms; and mental disorders. Associations with tobacco use disorder, respiratory conditions, and genitourinary conditions persisted after accounting for genetic overlap between depression and other psychiatric traits. Temporal analyses of time-at-first-diagnosis indicated that depression disproportionately preceded chronic pain and substance-related disorders, while asthma disproportionately preceded depression. CONCLUSIONS: The present results can inform the biological links between depression and both mental and systemic diseases. Although MDD polygenic risk scores cannot currently forecast health outcomes with precision at the individual level, as molecular-genetic discoveries for depression increase, these tools may augment risk prediction for medical and psychiatric conditions.

Use of Population-Level Administrative Data in Developmental Science.

Population-level administrative data-data on individuals' interactions with administrative systems (e.g., health, criminal justice, and education)-have substantially advanced our understanding of life-course development. In this review, we focus on five areas where research using these data has made significant contributions to developmental science: (a) understanding small or difficult-to-study populations, (b) evaluating intergenerational and family influences, (c) enabling estimation of causal effects through natural experiments and regional comparisons, (d) identifying individuals at risk for negative developmental outcomes, and (e) assessing neighborhood and environmental influences. Further advances will be made by linking prospective surveys to administrative data to expand the range of developmental questions that can be tested; supporting efforts to establish new linked administrative data resources, including in developing countries; and conducting cross-national comparisons to test findings' generalizability. New administrative data initiatives should involve consultation with population subgroups including vulnerable groups, efforts to obtain social license, and strong ethical oversight and governance arrangements.