Advantageous early-life environments cushion the genetic risk for ischemic heart disease.

In one of the first papers on the impact of early-life conditions on individuals' health in older age, Barker and Osmond [Lancet, 327, 1077-1081 (1986)] show a strong positive relationship between infant mortality rates in the 1920s and ischemic heart disease in the 1970s. We merge historical data on infant mortality rates to 370,000 individual records in the UK Biobank using information on local area and year of birth. We replicate the association between the early-life infant mortality rate and later-life ischemic heart disease in our sample. We then go "beyond Barker," by showing considerable genetic heterogeneity in this association that is robust to within-area as well as within-family analyses. We find no association between the polygenic index and heart disease in areas with the lowest infant mortality rates, but a strong positive relationship in areas characterized by high infant mortality. These findings suggest that advantageous environments can cushion one's genetic disease risk.

Hinge craniotomy versus standard decompressive hemicraniectomy: an experimental preclinical comparative study.

INTRODUCTION: Decompressive craniectomy (DC) is the most common surgical procedure to manage increased intracranial pressure (ICP). Hinge craniotomy (HC), which consists of fixing the bone operculum with a pivot, is an alternative method conceived to avoid some DC-related complications; nonetheless, it is debated whether it can provide enough volume expansion. In this study, we aimed to analyze the volume and ICP obtained with HC using an experimental cadaver-based preclinical model and compare the results to baseline and DC. METHODS: Baseline conditions, HC, and DC were compared on both sides of five anatomical specimens. Volume and ICP values were measured with a custom-made system. Local polynomial regression was used to investigate volume differences. RESULTS: The area of the bone opercula resulting from measurements was 115.55 cm2; the mean supratentorial volume was 955 mL. HC led to intermediate results compared to baseline and DC. At an ICP of 50 mmHg, HC offers 130 mL extra space but 172 mL less than a DC. Based on local polynomial regression, the mean volume difference between HC and the standard craniotomy was 10%; 14% between DC and HC; both are higher than the volume of brain herniation reported in the literature in the clinical setting. The volume leading to an ICP of 50 mmHg at baseline was less than the volume needed to reach an ICP of 20 mmHg after HC (10.05% and 14.95% from baseline, respectively). CONCLUSIONS: These data confirm the efficacy of HC in providing sufficient volume expansion. HC is a valid intermediate alternative in case of potentially evolutionary lesions and non-massive edema, especially in developing countries.

Challenges in studying the interplay of genes and environment. A study of childhood financial distress moderating genetic predisposition for peak smoking.

Smoking is one of the leading causes of preventable disease and death in the U.S., and it is strongly influenced both by genetic predisposition and childhood adversity. Using polygenic indices (PGIs) of predisposition to smoking, we evaluate whether childhood financial distress (CFD; a composite measure of financial adversity) moderates genetic risk in explaining peak-cigarette consumption in adulthood. Using the Health and Retirement Study (HRS), we find a substantial reduction in the relationship between genetic risk and peak smoking for those who did not suffer financial adversity in childhood. Among adult smokers who grew up in high-CFD households, a one standard deviation higher PGI is associated with 2.9 more cigarettes smoked per day at peak. By contrast, among smokers who grew up in low-CFD households, this gradient is reduced by 37 percent (or 1.1 fewer). These results are robust to controlling for a host of prime confounders. By contrast, we find no evidence of interactions between the PGI and typical measures of childhood SES such as parental education - a null result that we replicate in the Wisconsin Longitudinal Study (WLS) and the English Longitudinal Study of Aging (ELSA). This suggests the role of childhood financial distress in the relationship with peak smoking is distinct from that of low childhood SES, with high CFD potentially reflecting more acute distress than do measures of low childhood SES. Our evidence also suggests low childhood SES is a weaker proxy for acute distress, providing an alternative explanation for the childhood SES null result.

Evaluation of the Reggio Approach to Early Education.

We evaluate the Reggio Approach using non-experimental data on individuals from the cities of Reggio Emilia, Parma and Padova belonging to one of five age cohorts: ages 50, 40, 30, 18, and 6 as of 2012. The treated were exposed to municipally offered infant-toddler (ages 0-3) and preschool (ages 3-6) programs. The control group either did not receive formal childcare or were exposed to programs offered by the state or religious systems. We exploit the city-cohort structure of the data to estimate treatment effects using three strategies: difference-in-differences, matching, and matched-difference-in-differences. Most positive and significant effects are generated from comparisons of the treated with individuals who did not receive formal childcare. Relative to not receiving formal care, the Reggio Approach significantly boosts outcomes related to employment, socio-emotional skills, high school graduation, election participation, and obesity. Comparisons with individuals exposed to alternative forms of childcare do not yield strong patterns of positive and significant effects. This suggests that differences between the Reggio Approach and other alternatives are not sufficiently large to result in significant differences in outcomes. This interpretation is supported by our survey, which documents increasing similarities in the administrative and pedagogical practices of childcare systems in the three cities over time.

Trajectories of Early Childhood Skill Development and Maternal Mental Health.

We investigate the impacts of a perinatal psychosocial intervention on trajectories of maternal mental health and child skills, from birth to age 3. We find improved maternal mental health and functioning (0.17 to 0.29 SD), modest but imprecisely estimated improvements in parenting (0.07 to 0.11 SD), and transitory improvements in child socioemotional development (0.06 to 0.39 SD). The intervention had negligible influence on physical health and cognition. Estimates of a skill production function reveal the intervention attenuated the negative association between maternal depression and child outcomes, and narrowed outcome gaps between mothers who were and were not depressed in pregnancy.

Overcoming attenuation bias in regressions using polygenic indices.

Measurement error in polygenic indices (PGIs) attenuates the estimation of their effects in regression models. We analyze and compare two approaches addressing this attenuation bias: Obviously Related Instrumental Variables (ORIV) and the PGI Repository Correction (PGI-RC). Through simulations, we show that the PGI-RC performs slightly better than ORIV, unless the prediction sample is very small (N < 1000) or when there is considerable assortative mating. Within families, ORIV is the best choice since the PGI-RC correction factor is generally not available. We verify the empirical validity of the simulations by predicting educational attainment and height in a sample of siblings from the UK Biobank. We show that applying ORIV between families increases the standardized effect of the PGI by 12% (height) and by 22% (educational attainment) compared to a meta-analysis-based PGI, yet estimates remain slightly below the PGI-RC estimates. Furthermore, within-family ORIV regression provides the tightest lower bound for the direct genetic effect, increasing the lower bound for the standardized direct genetic effect on educational attainment from 0.14 to 0.18 (+29%), and for height from 0.54 to 0.61 (+13%) compared to a meta-analysis-based PGI.

Genetic contributions of noncognitive skills to academic development.

Noncognitive skills such as motivation and self-regulation, predict academic achievement beyond cognitive skills. However, the role of genetic and environmental factors and of their interplay in these developmental associations remains unclear. We provide a comprehensive account of how cognitive and noncognitive skills contribute to academic achievement from ages 7 to 16 in a sample of >10,000 children from England and Wales. Results indicated that noncognitive skills become increasingly predictive of academic achievement across development. Triangulating genetic methods, including twin analyses and polygenic scores (PGS), we found that the contribution of noncognitive genetics to academic achievement becomes stronger over development. The PGS for noncognitive skills predicted academic achievement developmentally, with prediction nearly doubling by age 16, pointing to gene-environment correlation (rGE). Within-family analyses indicated both passive and active/evocative rGE processes driven by noncognitive genetics. By studying genetic effects through a developmental lens, we provide novel insights into the role of noncognitive skills in academic development.

Genetic contributions of noncognitive skills to academic development.

Noncognitive skills such as motivation and self-regulation, are partly heritable and predict academic achievement beyond cognitive skills. However, how the relationship between noncognitive skills and academic achievement changes over development is unclear. The current study examined how cognitive and noncognitive skills contribute to academic achievement from ages 7 to 16 in a sample of over 10,000 children from England and Wales. Noncognitive skills were increasingly predictive of academic achievement across development. Twin and polygenic scores analyses found that the contribution of noncognitive genetics to academic achievement became stronger over the school years. Results from within-family analyses indicated that associations with noncognitive genetics could not simply be attributed to confounding by environmental differences between nuclear families and are consistent with a possible role for evocative/active gene-environment correlations. By studying genetic effects through a developmental lens, we provide novel insights into the role of noncognitive skills in academic development.

Cohort profile: Genetic data in the German Socio-Economic Panel Innovation Sample (SOEP-G).

The German Socio-Economic Panel (SOEP) serves a global research community by providing representative annual longitudinal data of respondents living in private households in Germany. The dataset offers a valuable life course panorama, encompassing living conditions, socioeconomic status, familial connections, personality traits, values, preferences, health, and well-being. To amplify research opportunities further, we have extended the SOEP Innovation Sample (SOEP-IS) by collecting genetic data from 2,598 participants, yielding the first genotyped dataset for Germany based on a representative population sample (SOEP-G). The sample includes 107 full-sibling pairs, 501 parent-offspring pairs, and 152 triads, which overlap with the parent-offspring pairs. Leveraging the results from well-powered genome-wide association studies, we created a repository comprising 66 polygenic indices (PGIs) in the SOEP-G sample. We show that the PGIs for height, BMI, and educational attainment capture 22∼24%, 12∼13%, and 9% of the variance in the respective phenotypes. Using the PGIs for height and BMI, we demonstrate that the considerable increase in average height and the decrease in average BMI in more recent birth cohorts cannot be attributed to genetic shifts within the German population or to age effects alone. These findings suggest an important role of improved environmental conditions in driving these changes. Furthermore, we show that higher values in the PGIs for educational attainment and the highest math class are associated with better self-rated health, illustrating complex relationships between genetics, cognition, behavior, socio-economic status, and health. In summary, the SOEP-G data and the PGI repository we created provide a valuable resource for studying individual differences, inequalities, life-course development, health, and interactions between genetic predispositions and the environment.

Effects of a maternal psychosocial intervention on hair derived biomarkers of HPA axis function in mothers and children in rural Pakistan.

Objective: Disruptions in the hypothalamic-pituitary-adrenal (HPA) axis are thought to be key neuroendocrine mechanisms involved in psychopathology and may have intergenerational impacts. Hair-derived HPA hormones offer a measure of long-term HPA axis activity that may be useful in assessing maternal and infant health. Building on a community-based randomized control trial of a perinatal depression intervention in Pakistan, we examine intervention effects on HPA axis activity in a subsample of mothers and infants. Methods: HPA axis activity was assessed using hair-derived cortisol, cortisone, and dehydroepiandosterone (DHEA). Hair samples were collected from mother-child dyads at one year postpartum from prenatally depressed women randomized to a cognitive-behavioral intervention (n = 35 dyads) or to enhanced usual care (n = 37 dyads), and from a comparison sample of women who screened negative for depression in pregnancy (n = 35 dyads). Results: The intervention group had 38 percent (p=0.01) lower maternal cortisol levels and 45 percent (p < 0.01) lower maternal cortisone compared to the EUC group. Maternal DHEA levels were higher among women in the intervention group compared to the EUC group by 29 percent (p = 0.02). Intergenerational intervention effects show higher DHEA levels in infants by 43% (p = 0.03). Infant cortisol and cortisone did not differ across groups. Conclusions: Results suggest that the perinatal depression intervention has effects on HPA axis activity in both mothers and children, providing evidence that treating maternal depression may impact physiological stress system functioning intergenerationally. In addition, utilizing hair-derived biomarkers of HPA-axis activity is a potentially useful clinical indicator of intervention impacts on the neuroendocrine system.

Family Life in Lockdown.

The lockdown imposed following the COVID-19 pandemic of spring 2020 dramatically changed the daily lives and routines of millions of people worldwide. We analyze how such changes contributed to patterns of activity within the household using a novel survey of Italian, British, and American families in lockdown. A high percentage report disruptions in the patterns of family life, manifesting in new work patterns, chore allocations, and household tensions. Though men have taken an increased share of childcare and grocery shopping duties, reallocations are not nearly as stark as disruptions to work patterns might suggest, and families having to reallocate duties report greater tensions. Our results highlight tightened constraints budging up against stable and gendered patterns of intra-household cooperation norms. While the long-run consequences of the COVID-19 lockdown on family life cannot be assessed at this stage, we point toward the likely opportunities and challenges.

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.

Effectiveness of a peer-delivered, psychosocial intervention on maternal depression and child development at 3 years postnatal: a cluster randomised trial in Pakistan.

BACKGROUND: Maternal depression has a recurring course that can influence offspring outcomes. Evidence on how to treat maternal depression to improve longer-term maternal outcomes and reduce intergenerational transmission of psychopathology is scarce, particularly for task-shifted, low-intensity, and scalable psychosocial interventions. We evaluated the effects of a peer-delivered, psychosocial intervention on maternal depression and child development at 3 years postnatal. METHODS: 40 village clusters in Pakistan were randomly allocated using a computerised randomisation sequence to receive a group-based, psychosocial intervention and enhanced usual care for 36 months, or enhanced usual care alone. Pregnant women (≥18 years) were screened for moderate or severe symptoms of depression (patient health questionnaire-9 [PHQ-9] score ≥10) and were recruited into the trial (570 participants), and a cohort without depression (PHQ-9 score <10) was also enrolled (584 participants). Including the non-depressed dyads enabled us to determine how much of the excess risk due to maternal depression exposure the intervention could mitigate. Research teams responsible for identifying, obtaining consent, and recruiting trial participants were blind to the allocation status throughout the duration of the study, and principal investigators, site coordinators, statisticians, and members of the trial steering committee were also blinded to the allocation status until the analysis of 6-month data for the intervention. Primary outcomes were maternal depression symptoms and remission (PHQ-9 score <10) and child socioemotional skills (strengths and difficulties questionnaire [SDQ-TD]) at 36-months postnatal. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, NCT02658994. FINDINGS: From Oct 15, 2014 to Feb 25, 2016 46 village clusters were assessed for eligibility, of which 40 (including 1910 mothers were enrolled. After exclusions, 288 women were randomly assigned to the enhanced usual care group and 284 to the intervention group, and 1159 women were included in a group without prenatal depression. At 36-months postnatal, complete data were available from 889 mother-child dyads: 206 (72·5%) in the intervention group, 216 (75·3%) in the enhanced usual care group, and 467 (80·0%) women who did not have prenatal-depression. We did not observe significant outcome differences between the intervention group and the enhanced usual care group for the primary outcomes. The standardised mean difference of PHQ-9 total score was -0·13 (95% CI -0·33 to 0·07), relative risk of patient health questionnaire-9 remission was 1·00 (95% CI 0·88 to 1·14), and the SDQ-TD treatment estimate was -0·10 (95% CI -1·39 to 1·19). INTERPRETATION: Reduced symptom severity and high remission rates were seen across both the intervention and enhanced usual care groups, possibly masking any effects of the intervention. A multi-year, psychosocial intervention can be task-shifted via peers but might be susceptible to reductions in fidelity and dosage over time (which were not among the outcomes of this trial). Early intervention efforts might need to rely on multiple models (eg, collaborative care), be of greater intensity, and potentially targeted at mothers who are at high risk for depression to reduce the intergenerational transmission of psychopathology from mothers to children. FUNDING: National Institutes of Health.

Father involvement in the first year of life: Associations with maternal mental health and child development outcomes in rural Pakistan.

The contribution of fathers to child development and maternal mental health is increasingly acknowledged, although research on this topic outside of high income countries is limited. Using longitudinal data, we characterized father involvement in a rural setting in Pakistan and investigated the link between father involvement in the first year of life and child development and maternal depression. Data come from the Bachpan study, a birth cohort established in the context of a perinatal depression intervention. Father involvement was mother reported at 3 and 12 months postpartum and covered domains such as playing with or soothing the infant. Child outcomes included growth at 3, 6 and 12 months postpartum, socioemotional development at 6 months (Ages and Stages Questionnaire-socioemotional), and developmental milestones at 12 months (Bayley Scales of Infant and Toddler Development, BSID)). Maternal depression was assessed at 3, 6, and 12 months postpartum. Roughly 20% of the fathers were temporarily non-resident. Among the rest, most mothers reported that fathers were involved: for example, approximately 40% reported that the father plays with the baby on a typical day. We observed no clear pattern of association between 3-month father involvement and child growth at any time point; however, 12-month father involvement was cross-sectionally inversely associated with child growth. We observed a protective pattern of association between 3-month father involvement and 6-month child socioemotional development. For the BSID domains, while almost all effect estimates suggested a protective association with higher levels of father involvement/father being temporarily non-resident, the magnitude of the estimates was smaller and most 95% confidence intervals crossed the null. Finally, there was a trend toward greater father involvement/being temporary non-resident predicting lower levels of maternal depression. Using longitudinal data, these results provide new evidence about the association between father involvement, and both child development and maternal mental health.

Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences.

Humans vary substantially in their willingness to take risks. In a combined sample of over 1 million individuals, we conducted genome-wide association studies (GWAS) of general risk tolerance, adventurousness, and risky behaviors in the driving, drinking, smoking, and sexual domains. Across all GWAS, we identified hundreds of associated loci, including 99 loci associated with general risk tolerance. We report evidence of substantial shared genetic influences across risk tolerance and the risky behaviors: 46 of the 99 general risk tolerance loci contain a lead SNP for at least one of our other GWAS, and general risk tolerance is genetically correlated ([Formula: see text] ~ 0.25 to 0.50) with a range of risky behaviors. Bioinformatics analyses imply that genes near SNPs associated with general risk tolerance are highly expressed in brain tissues and point to a role for glutamatergic and GABAergic neurotransmission. We found no evidence of enrichment for genes previously hypothesized to relate to risk tolerance.