Interactions between Genetic, Prenatal, Cortisol, and Parenting Influences on Adolescent Substance Use and Frequency:A TRAILS Study

INTRODUCTION: Dynamic relations between genetic, hormone, and pre- and postnatal environments are theorized as critically important for adolescent substance use but are rarely tested in multifactorial models. This study assessed the impact of interactions of genetic risk and cortisol reactivity with prenatal and parenting influences on both any and frequency of adolescent substance use. METHODS: Data are from the TRacking Adolescents' Individual Lives Survey (TRAILS), a prospective longitudinal, multi-rater study of 2,230 Dutch adolescents. Genetic risk was assessed via 3 substance-specific polygenic scores. Mothers retrospectively reported prenatal risk when adolescents were 11 years old. Adolescents rated their parents' warmth and hostility at age 11. Salivary cortisol reactivity was measured in response to a social stress task at age 16. Adolescents' self-reported cigarette, alcohol, and cannabis use frequency at age 16. RESULTS: A multivariate hurdle regression model showed that polygenic risk for smoking, alcohol, and cannabis predicted any use of each substance, respectively, but predicted more frequent use only for smoking. Blunted cortisol reactivity predicted any use and more frequent use for all 3 outcomes. There were 2 interactions: blunted cortisol reactivity exacerbated the association of polygenic risk with any smoking and the association of prenatal risk with any alcohol use. CONCLUSION: Polygenic risk seems of importance for early use but less so for frequency of use, whereas blunted cortisol reactivity was correlated with both. Blunted cortisol reactivity may also catalyze early risks for substance use, though to a limited degree. Gene-environment interactions play no role in the context of this multifactorial model

Maternal Smoking During Pregnancy and Offspring Birth Weight: A Genetically-Informed Approach Comparing Multiple Raters

Maternal smoking during pregnancy (SDP) is a significant public health concern with adverse consequences to the health and well-being of the fetus. There is considerable debate about the best method of assessing SDP, including birth/medical records, timeline follow-back approaches, multiple reporters, and biological verification (e.g., cotinine). This is particularly salient for genetically-informed approaches where it is not always possible or practical to do a prospective study starting during the prenatal period when concurrent biological specimen samples can be collected with ease. In a sample of families (N = 173) specifically selected for sibling pairs discordant for prenatal smoking exposure, we: (1) compare rates of agreement across different types of report—maternal report of SDP, paternal report of maternal SDP, and SDP contained on birth records from the Department of Vital Statistics; (2) examine whether SDP is predictive of birth weight outcomes using our best SDP report as identified via step (1); and (3) use a sibling-comparison approach that controls for genetic and familial influences that siblings share in order to assess the effects of SDP on birth weight. Results show high agreement between reporters and support the utility of retrospective report of SDP. Further, we replicate a causal association between SDP and birth weight, wherein SDP results in reduced birth weight even when accounting for genetic and familial confounding factors via a sibling comparison approac

Passive \u3cem\u3er\u3c/em\u3eGE or Developmental Gene-Environment Cascade? An Investigation of the Role of Xenobiotic Metabolism Genes in the Association Between Smoke Exposure During Pregnancy and Child Birth Weight

There is considerable evidence that smoke exposure during pregnancy (SDP) environmentally influences birth weight after controlling for genetic influences and maternal characteristics. However, maternal smoking during pregnancy—the behavior that leads to smoke exposure during pregnancy—is also genetically-influenced, indicating the potential role of passive gene-environment correlation. An alternative to passive gene-SDP correlation is a cascading effect whereby maternal and child genetic influences are causally linked to prenatal exposures, which then have an ‘environmental’ effect on the development of the child’s biology and behavior. We describe and demonstrate a conceptual framework for disentangling passive rGE from this cascading GE effect using a systems-based polygenic scoring approach comprised of genes shown to be important in the xenobiotic (substances foreign to the body) metabolism pathway. Data were drawn from 5044 families from the Avon Longitudinal Study of Parents and Children with information on maternal SDP, birth weight, and genetic polymorphisms in the xenobiotic pathway. Within a k-fold cross-validation approach (k = 5), we created weighted maternal and child polygenic scores using 18 polymorphisms from 10 genes that have been implicated in the xenobiotic metabolism pathway. Mothers and children shared variation in xenobiotic metabolism genes. Amongst mothers who smoked during pregnancy, neither maternal nor child xenobiotic metabolism polygenic scores were associated with a higher likelihood of smoke exposure during pregnancy, or the severity of smoke exposure during pregnancy (and therefore, neither proposed mechanism was supported), or with child birth weight. SDP was consistently associated with lower child birth weight controlling for the polygenic scores, maternal educational attainment, social class, psychiatric problems, and age. Limitations of the study design and the potential of the framework using other designs are discussed

The effect of smoking during pregnancy on severity and directionality of externalizing and internalizing symptoms: A genetically informed approach

The objective was to examine the association between maternal smoking during pregnancy (SDP) and (I) severity and (II) directionality of externalizing and internalizing symptoms in a sample of sibling pairs while rigorously controlling for familial confounds. The Missouri Mothers and Their Children Study is a family study (N = 173 families) with sibling pairs (aged 7 to 16 years) who are discordant for exposure to SDP. This sibling comparison study is designed to disentangle the effects of SDP from familial confounds. An SDP severity score was created for each child using a combination of SDP indicators (timing, duration, and amount). Principal component analysis of externalizing and internalizing behavior, assessed with the Child Behavior Checklist and Teacher Report Form, was used to create symptom severity and directionality scores. The variance in severity and directionality scores was primarily a function of differences between siblings (71% and 85%, respectively) rather than differences across families (29% and 15%, respectively). The severity score that combines externalizing and internalizing symptom severity was not associated with SDP. However, a significant within-family effect of SDP on symptom directionality (b = 0.07

Missouri mothers and their children: A family study of the effects of genetics and the prenatal environment

The Missouri Mothers and Their Children Study was specifically designed to critically investigate prenatal environmental influences on child attention problems and associated learning and cognitive deficits. The project began as a pilot study in 2004 and was formally launched in 2008. Participants in the study were initially identified via the Department of Vital Statistics birth record database. Interview and lab-based data were obtained from (1) mothers of Missouri-born children (born 1998–2005), who smoked during one pregnancy but not during another pregnancy, (2) biological fathers when available, and (3) the children [i.e., full sibling pairs discordant for exposure to maternal smoking during pregnancy (SDP)]. This within-mother, between-pregnancy contrast provides the best possible methodological control for many stable maternal and familial confounding factors (e.g., heritable and socio-demographic characteristics of the mother that predict increased probability of SDP). It also controls for differences between mothers who do and do not smoke during pregnancy, and their partners, that might otherwise artifactually create, or alternatively mask, associations between SDP and child outcomes. Such a design will therefore provide opportunities to determine less biased effect sizes while also allowing us to investigate (on a preliminary basis) the possible contribution of paternal or other second-hand smoke exposure during the pre-, peri- and postnatal periods to offspring outcome. This protocol has developed a cohort that can be followed longitudinally through periods typically associated with increased externalizing symptoms and substance use initiation

Correspondence between hair cortisol concentrations and 30-day integrated daily salivary and weekly urinary cortisol measures

Characterization of cortisol production, regulation and function is of considerable interest and relevance given its ubiquitous role in virtually all aspects of physiology, health and disease risk. The quantification of cortisol concentration in hair has been proposed as a promising approach for the retrospective assessment of integrated, long-term cortisol production. However, human research is still needed to directly test and validate current assumptions about which aspects of cortisol production and regulation are reflected in hair cortisol concentrations (HCC). Here, we report findings from a validation study in a sample of 17 healthy adults (mean ± SD age: 34 ± 8.6 yrs). To determine the extent to which HCC captures cumulative cortisol production, we examined the correspondence of HCC, obtained from the first 1cm scalp-near hair segment, assumed to retrospectively reflect 1-month integrated cortisol secretion, with 30-day average salivary cortisol area-under-the curve (AUC) based on 3 samples collected per day (on awakening, +30 min, at bedtime) and the average of 4 weekly 24-hr urinary free cortisol (UFC) assessments. To further address which aspects of cortisol production and regulation are best reflected in the HCC measure, we also examined components of the salivary measures that represent: 1) production in response to the challenge of awakening (using the cortisol awakening response [CAR]), and 2) chronobiological regulation of cortisol production (using diurnal slope). Finally, we evaluated the test-retest stability of each cortisol measure. Results indicate that HCC was most strongly associated with the prior 30-day integrated cortisol production measure (average salivary cortisol AUC) (r = 0.61, p = 0.01). There were no significant associations between HCC and the 30-day summary measures using CAR or diurnal slope. The relationship between 1-month integrated 24-hr UFC and HCC did not reach statistical significance (r = 0.30, p = 0.28). Lastly, of all cortisol measures, test-retest correlations of serial measures were highest for HCC (month-to-month: r = 0.84, p < 0.001), followed by 24-hr UFC (week-to-week: r’s between 0.59 and 0.68, ps < 0.05) and then integrated salivary cortisol concentrations (week-to-week: r’s between 0.38 and 0.61, p’s between 0.13 and 0.01). These findings support the contention that HCC provides a reliable estimate of long-term integrated free cortisol production that is aligned with integrated salivary cortisol production measured over a corresponding one-month period

The Prenatal Environment in Twin Studies: A Review on Chorionicity

A literature search was conducted to identify articles examining the association of chorionicity (e.g., whether twins share a single chorion and thus placenta or have separate chorions/placentas) and genetics, psychiatry/behavior, and neurological manifestations in humans twins and higher-order multiples. The main aim was to assess how frequently chorionicity has been examined in relation to heritability estimates, and to assess which phenotypes may be most sensitive to, or affected by, bias in heritability estimates because of chorionicity. Consistent with the theory that some chorionicity effects could lead to overestimation and others to underestimation of heritability, there were instances of each across the many phenotypes reviewed. However, firm conclusions should not be drawn since some of the outcomes were only examined in one or few studies and often sample sizes were small. While the evidence for bias due to chorionicity was mixed or null for many outcomes, results do, however, consistently suggest that heritability estimates are underestimated for measures of birth weight and early growth when chorionicity is not taken into account

Ultra-rapid development and deployment of a family resilience program during the COVID-19 pandemic: Lessons learned from Families Tackling Tough Times Together

The 2020 COVID-19 pandemic brought uncertainty, anxiety, and stress into households; however, it also created an opportunity as many families, sequestered at home, found themselves spending much more time together. To support families and improve their ability to cope, recover, and build resilience amid the pandemic, Purdue University’s College of Health and Human Sciences (HHS) launched Families Tackling Tough Times Together (FT), a strength-based multi-week online program informed by scientific evidence about family resilience. Offered through a Facebook group, FT targeted parents or caregivers, children, youth, young adults, older adults, and helping professionals serving families. FT was designed to appeal to both military and civilian families, in part because both groups were experiencing similar challenges associated with the pandemic. This was not only an opportunity to bring civilian and military families together, but also for civilian families to learn from the experiences of military families in surmounting significant challenges. This article describes the development and implementation of the FT program, as well as lessons learned. Strategies highlighted in this article may be helpful to researchers or practitioners who wish to implement a rapid-response intervention aimed at building family resilience