Causal inference methods for intergenerational research using observational data

Identifying early causal factors leading to the development of poor mental health and behavioral outcomes is essential to design efficient preventive interventions. The substantial associations observed between parental risk factors (e.g., maternal stress in pregnancy, parental education, parental psychopathology, parent-child relationship) and child outcomes point toward the importance of parents in shaping child outcomes. However, such associations may also reflect confounding, including genetic transmission-that is, the child inherits genetic risk common to the parental risk factor and the child outcome. This can generate associations in the absence of a causal effect. As randomized trials and experiments are often not feasible or ethical, observational studies can help to infer causality under specific assumptions. This review aims to provide a comprehensive summary of current causal inference methods using observational data in intergenerational settings. We present the rich causal inference toolbox currently available to researchers, including genetically informed and analytical methods, and discuss their application to child mental health and related outcomes. We outline promising research areas and discuss how existing approaches can be combined or extended to probe the causal nature of intergenerational effects. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

Validation of a German Version of the Stress Overload Scale and Comparison of Different Time Frames in the Instructions

Abstract: Introduction: The Stress Overload Scale (SOS; Amirkhan, 2012 , 2018 ) was introduced as a two-factorial self-report measure of stress to overcome limitations of other scales. Methods: We developed a German translation of the SOS and validated it in addition to a short version and an extra-short version. Furthermore, we tested whether manipulating the time frame introduced as retention interval in the instructions affected its psychometric properties. Results: Using two independent age-heterogeneous convenience samples ( Ntotal = 1,239), we found good psychometric properties for a modified German short version of the SOS-S (SOS-S-G) and a new extra-short version (SOS-XS-G), but not for the German long version of the SOS. Moreover, manipulating the time frame of the SOS did not affect its psychometric quality. Discussion The SOS enriches the repertoire of self-report measures of stress as it captures the nonpathological core facets of stress in line with theoretical stress conceptualizations

Das ILZNAWI-Modell: Inklusive Lernzugänge im naturwissenschaftlichen Unterricht. Zur Planbarkeit von Individualisierung und Kooperation am Gemeinsamen Gegenstand

Der Beitrag stellt das im Rahmen des Projekts „Reckahner Modelle zur inklusiven Unterrichtsplanung“ (REMI) entwickelte ILZNAWI-Modell („Inklusive Lernzugänge im naturwissenschaftlichen Unterricht“) vor. Es dient dazu, den Gemeinsamen Gegenstand im naturwissenschaftlichen Unterricht inklusionsförderlich und heterogenitätssensibel auszudifferenzieren und bildet auf Grundlage eines weiten Inklusionsverständnisses gestufte Lernzugänge und Abstraktionsgrade ab. Der Artikel gibt einen Überblick über diesbezüglich bestehende Forschungsprojekte und Unterrichtskonzepte, leitet hieraus die Notwendigkeit für das Modell ab und anschließend dessen Entwicklung theoretisch her. Anhand ausgewählter Stufenmodelle für die Fächer Biologie, Physik und Chemie wird die Planungsanwendung konkretisiert. In einer Unterrichtssequenz zur Evolution des Menschen werden Möglichkeiten zur Verbindung von Individualisierung und Kooperation aufgezeigt. Weitere Umsetzungsideen der Fächer Chemie und Physik verdeutlichen die Bandbreite an Nutzungsmöglichkeiten des Modells. (DIPF/Orig.

No long-term effects of antenatal synthetic glucocorticoid exposure on epigenetic regulation of stress-related genes

Antenatal synthetic glucocorticoid (sGC) treatment is a potent modifier of the hypothalamic-pituitary-adrenal (HPA) axis. In this context, epigenetic modifications are discussed as potential regulators explaining how prenatal exposure to GCs might translate into persistent changes of HPA axis “functioning”. The purpose of this study was to investigate whether DNA methylation and gene expression profiles of stress-associated genes (NR3C1; FKBP5; SLC6A4) may mediate the persistent effects of sGC on cortisol stress reactivity that have been previously observed. In addition, hair cortisol concentrations (hairC) were investigated as a valid biomarker of long-term HPA axis activity. This cross-sectional study comprised 108 term-born children and adolescents, including individuals with antenatal GC treatment and controls. From whole blood, DNA methylation was analyzed by targeted deep bisulfite sequencing. Relative mRNA expression was determined by RT-qPCR experiments and qBase analysis. Acute stress reactivity was assessed by the Trier Social Stress Test (TSST) measuring salivary cortisol by ELISA and hairC concentrations were determined from hair samples by liquid chromatography coupled with tandem mass spectrometry. First, no differences in DNA methylation and mRNA expression levels of the stress-associated genes between individuals treated with antenatal sGC compared to controls were found. Second, DNA methylation and mRNA expression levels were neither associated with cortisol stress reactivity nor with hairC. These findings do not corroborate the belief that DNA methylation and mRNA expression profiles of stress-associated genes (NR3C1; FKBP5; SLC6A4) play a key mediating role of the persistent effects of sGC on HPA axis functioning

Resting heart rate and antisocial behaviour: a Mendelian randomisation study

Observational studies frequently report phenotypic associations between low resting heart rate (RHR) and higher levels of antisocial behaviour (ASB), although it remains unclear whether this relationship reflects causality. To triangulate evidence, we conducted two-sample univariable Mendelian randomisation (MR), multivariable MR and linkage disequilibrium score regression (LDSC) analyses. Genetic data were accessed from published genome-wide association studies (GWAS) for RHR (n = 458,835) and ASB (n = 85,359) for the univariable analyses, along with a third GWAS for heart rate variability (HRV; n = 53,174) for all other analyses. Genome-wide significant (p < 5 × 10-8) single-nucleotide polymorphisms associated with RHR (n = 278) were selected as instrumental variables and the outcome was a composite measure of ASB. No causal association was observed between RHR and ASB (BIVW =  - 0.0004, p = 0.841). The multivariable MR analyses including RHR and HRV also suggested no causal associations (BIVW = 0.016, p = 0.914) and no genetic correlations between the heart rate measures and ASB were observed using LDSC (rg = 0.057, p = 0.169). Sensitivity analyses suggested that our results are not likely to be affected by heterogeneity, pleiotropic effects, or reverse causation. These findings suggest that individual differences in autonomic nervous system functioning indexed by RHR are not likely to directly contribute to the development of ASB. Therefore, previously observed associations between RHR and ASB may arise from confounding, reverse causation, and/or additional study characteristics. Further causally informative longitudinal research is required to confirm our findings, and caution should be applied when using measures of RHR in interventions targeting ASB

High-rate low-temperature dc pulsed magnetron sputtering of photocatalytic TiO2films: the effect of repetition frequency

The article reports on low-temperature high-rate sputtering of hydrophilic transparent TiO2thin films using dc dual magnetron (DM) sputtering in Ar + O2mixture on unheated glass substrates. The DM was operated in a bipolar asymmetric mode and was equipped with Ti(99.5) targets of 50 mm in diameter. The substrate surface temperature Tsurfmeasured by a thermostrip was less than 180 °C for all experiments. The effect of the repetition frequency frwas investigated in detail. It was found that the increase of frfrom 100 to 350 kHz leads to (a) an improvement of the efficiency of the deposition process that results in a significant increase of the deposition rate aDof sputtered TiO2films and (b) a decrease of peak pulse voltage and sustaining of the magnetron discharge at higher target power densities. It was demonstrated that several hundreds nm thick hydrophilic TiO2films can be sputtered on unheated glass substrates at aD = 80 nm/min, Tsurf < 180 °C when high value of fr = 350 kHz was used. Properties of a thin hydrophilic TiO2film deposited on a polycarbonate substrate are given

The DNA methylation landscape of the human oxytocin receptor gene (OXTR): data-driven clusters and their relation to gene expression and childhood adversity

The oxytocin receptor gene (OXTR) is of interest when investigating the effects of early adversity on DNA methylation. However, there is heterogeneity regarding the selection of the most promising CpG sites to target for analyses. The goal of this study was to determine functionally relevant clusters of CpG sites within the OXTR CpG island in 113 mother-infant dyads, with 58 of the mothers reporting childhood maltreatment (CM). OXTR DNA methylation was analyzed in peripheral/umbilical blood mononuclear cells. Different complexity reduction approaches were used to reduce the 188 CpG sites into clusters of co-methylated sites. Furthermore, associations between OXTR DNA methylation (cluster- and site-specific level) and OXTR gene expression and CM were investigated in mothers. Results showed that, first, CpG sections differed strongly regarding their statistical utility for research of individual differences in DNA methylation. Second, cluster analyses and Partial Least Squares (PLS) suggested two clusters consisting of intron1/exon2 and the protein-coding region of exon3, respectively, as most strongly associated with outcome measures. Third, cross-validated PLS regression explained 7% of variance in CM, with low cross-validated variance explained for the prediction of gene expression. Fourth, substantial mother-child correspondence was observed in correlation patterns within the identified clusters, but only modest correspondence outside these clusters. This study makes an important contribution to the mapping of the DNA methylation landscape of the OXTR CpG island by highlighting clusters of CpG sites that show desirable statistical properties and predictive value. We provide a Companion Web Application to facilitate the choice of CpG sites

Examining intergenerational risk factors for conduct problems using polygenic scores in the Norwegian Mother, Father and Child Cohort Study

The aetiology of conduct problems involves a combination of genetic and environmental factors, many of which are inherently linked to parental characteristics given parents' central role in children's lives across development. It is important to disentangle to what extent links between parental heritable characteristics and children's behaviour are due to transmission of genetic risk or due to parental indirect genetic influences via the environment (i.e., genetic nurture). We used 31,290 genotyped mother-father-child trios from the Norwegian Mother, Father and Child Cohort Study (MoBa), testing genetic transmission and genetic nurture effects on conduct problems using 13 polygenic scores (PGS) spanning psychiatric conditions, substance use, education-related factors, and other risk factors. Maternal or self-reports of conduct problems at ages 8 and 14 years were available for up to 15,477 children. We found significant genetic transmission effects on conduct problems for 12 out of 13 PGS at age 8 years (strongest association: PGS for smoking, β = 0.07, 95% confidence interval = [0.05, 0.08]) and for 4 out of 13 PGS at age 14 years (strongest association: PGS for externalising problems, β = 0.08, 95% confidence interval = [0.05, 0.11]). Conversely, we did not find genetic nurture effects for conduct problems using our selection of PGS. Our findings provide evidence for genetic transmission in the association between parental characteristics and child conduct problems. Our results may also indicate that genetic nurture via traits indexed by our polygenic scores is of limited aetiological importance for conduct problems-though effects of small magnitude or effects via parental traits not captured by the included PGS remain a possibility