Like No Other? A Family-Specific Network Approach to Parenting Adolescents.

Numerous theories suggest that parents and adolescents influence each other in diverse ways; however, whether these influences differ between subgroups or are unique to each family remains uncertain. Therefore, this study explored whether data-driven subgroups of families emerged that exhibited a similar daily interplay between parenting and adolescent affective well-being. To do so, Subgrouping Group Iterative Multiple Model Estimation (S-GIMME) was used to estimate family-specific dynamic network models, containing same- and next-day associations among five parenting practices (i.e., warmth, autonomy support, psychological control, strictness, monitoring) and adolescent positive and negative affect. These family-specific networks were estimated for 129 adolescents (Mage = 13.3, SDage = 1.2, 64% female, 87% Dutch), who reported each day on parenting and their affect for 100 consecutive days. The findings of S-GIMME did not identify data-driven subgroups sharing similar parenting-affect associations. Instead, each family displayed a unique pattern of temporal associations between the different practices and adolescent affect. Thus, the ways in which parenting practices were related to adolescents' affect in everyday life were family specific.

Effects of oxytocin and vasopressin administration on human fathers' sensitive and challenging parenting: A randomized within-subject controlled trial.

This randomized, double-blind, placebo-controlled within-subject study examined the effects of intranasal administration of oxytocin and vasopressin on fathers' sensitive and challenging parenting behaviors. Furthermore, we examined the moderating role of fathers' early childhood experiences. The sample consisted of 70 fathers with their 2- to 12-month-old infants. All fathers were assigned to each of the three experimental sessions (oxytocin, vasopressin, and placebo), on three separate days, with random order and intervening periods of one to two weeks. Sensitive and challenging parenting behaviors (CPB) were observed during a 10-minute free play task. Results showed no effects of vasopressin administration on paternal sensitivity. Fathers in the oxytocin condition were less sensitive than fathers in the placebo condition, and this effect was moderated by fathers' own childhood experiences: Fathers who reported higher levels of experienced parental love withdrawal were less sensitive in the oxytocin condition as compared to the placebo condition, whereas fathers with less experienced parental love withdrawal showed no difference in sensitivity between the oxytocin and placebo condition. No effects were found of oxytocin and vasopressin administration on fathers' CPB. Our results, although partly unexpected, are largely in line with previous literature showing that oxytocin administration can exert negative effects in individuals with adverse childhood experiences.

Maternal environmental risk factors and the development of internalizing and externalizing problems in childhood: The complex role of genetic factors.

The development of problem behavior in children is associated with exposure to environmental factors, including the maternal environment. Both are influenced by genetic factors, which may also be correlated, that is, environmental risk and problem behavior in children might be influenced by partly the same genetic factors. In addition, environmental and genetic factors could interact with each other increasing the risk of problem behavior in children. To date, limited research investigated these mechanisms in a genome-wide approach. Therefore, the goal of this study was to investigate the association between genetic risk for psychiatric and related traits, as indicated by polygenetic risk scores (PRSs), exposure to previously identified maternal risk factors, and problem behavior in a sample of 1,154 children from the Amsterdam Born Children and their Development study at ages 5-6 and 11-12 years old. The PRSs were derived from genome-wide association studies (GWASs) on schizophrenia, major depressive disorder, neuroticism, and wellbeing. Regression analysis showed that the PRSs were associated with exposure to multiple environmental risk factors, suggesting passive gene-environment correlation. In addition, the PRS based on the schizophrenia GWAS was associated with externalizing behavior problems in children at age 5-6. We did not find any association with problem behavior for the other PRSs. Our results indicate that genetic predispositions for psychiatric disorders and wellbeing are associated with early environmental risk factors for children's problem behavior.

The impact of childhood trauma and psychophysiological reactivity on at-risk women's adjustment to parenthood.

Adverse childhood experiences (ACEs) have an impact on women's adaptation to parenthood, but mechanisms are poorly understood. Autonomic nervous system reactivity was tested as a potential mediating mechanism in a sample of 193 at-risk primiparous women. ACEs were measured retrospectively during pregnancy. A baby cry-response task was administered during pregnancy while indicators of sympathetic reactivity (pre-ejection period; PEP) and parasympathetic reactivity (respiratory sinus arrhythmia; RSA) were recorded. Parenting self-efficacy, anxiety, and depressive symptoms were measured during pregnancy and 1 year after giving birth. Harsh discipline was measured 2 years after giving birth. Structural equation modeling was employed to test whether baseline PEP and RSA and reactivity mediated links between ACEs and postnatal outcomes, adjusted for prenatal variables. High ACEs predicted less RSA reactivity (p = .02), which subsequently predicted increases in depressive symptoms (p = .03). The indirect effect was not significant (p = .06). There was no indirect link between high ACEs and harsh parenting through PEP nor RSA (n = 98). The parasympathetic nervous system may be involved in negative affective responses in the transition to parenthood among women exposed to childhood trauma.

An Extended Twin-Pedigree Study of Neuroticism in the Netherlands Twin Register.

For the participants in the Netherlands Twin Register (NTR) we constructed the extended pedigrees which specify all relations among nuclear and larger twin families in the register. A total of 253,015 subjects from 58,645 families were linked to each other, to the degree that we had information on the relations among participants. We describe the algorithm that was applied to construct the pedigrees. For > 30,000 adolescent and adult NTR participants data were available on harmonized neuroticism scores. We analyzed these data in the Mendel software package (Lange et al., Bioinformatics 29(12):1568-1570, 2013) to estimate the contributions of additive and non-additive genetic factors. In contrast to much of the earlier work based on twin data rather than on extended pedigrees, we could also estimate the contribution of shared household effects in the presence of non-additive genetic factors. The estimated broad-sense heritability of neuroticism was 47%, with almost equal contributions of additive and non-additive (dominance) genetic factors. A shared household effect explained 13% and unique environmental factors explained the remaining 40% of the variance in neuroticism.

Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium.

Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion.

The genetics of alcohol dependence: Twin and SNP-based heritability, and genome-wide association study based on AUDIT scores.

Alcohol dependence (AD) is among the most common and costly public health problems contributing to morbidity and mortality throughout the world. In this study, we investigate the genetic basis of AD in a Dutch population using data from the Netherlands Twin Register (NTR) and the Netherlands Study of Depression and Anxiety (NESDA). The presence of AD was ascertained via the Alcohol Use Disorders Identification Test (AUDIT) applying cut-offs with good specificity and sensitivity in identifying those at risk for AD. Twin-based heritability of AD-AUDIT was estimated using structural equation modeling of data in 7,694 MZ and DZ twin pairs. Variance in AD-AUDIT explained by all SNPs was estimated with genome-wide complex trait analysis (GCTA). A genome-wide association study (GWAS) was performed in 7,842 subjects. GWAS SNP effect concordance analysis was performed between our GWAS and a recent AD GWAS using DSM-IV diagnosis. The twin-based heritability of AD-AUDIT was estimated at 60% (55-69%). GCTA showed that common SNPs jointly capture 33% (SE = 0.12, P = 0.002) of this heritability. In the GWAS, the top hits were positioned within four regions (4q31.1, 2p16.1, 6q25.1, 7p14.1) with the strongest association detected for rs55768019 (P = 7.58 × 10(-7) ). This first GWAS of AD using the AUDIT measure found results consistent with previous genetic studies using DSM diagnosis: concordance in heritability estimates and direction of SNPs effect and overlap with top hits from previous GWAS. Thus, the use of appropriate questionnaires may represent cost-effective strategies to phenotype samples in large-scale biobanks or other population-based datasets.

Loci affecting gamma-glutamyl transferase in adults and adolescents show age × SNP interaction and cardiometabolic disease associations.

Serum gamma-glutamyl transferase (GGT) activity is a marker of liver disease which is also prospectively associated with the risk of all-cause mortality, cardiovascular disease, type 2 diabetes and cancers. We have discovered novel loci affecting GGT in a genome-wide association study (rs1497406 in an intergenic region of chromosome 1, P = 3.9 × 10(-8); rs944002 in C14orf73 on chromosome 14, P = 4.7 × 10(-13); rs340005 in RORA on chromosome 15, P = 2.4 × 10(-8)), and a highly significant heterogeneity between adult and adolescent results at the GGT1 locus on chromosome 22 (maximum P(HET) = 5.6 × 10(-12) at rs6519520). Pathway analysis of significant and suggestive single-nucleotide polymorphism associations showed significant overlap between genes affecting GGT and those affecting common metabolic and inflammatory diseases, and identified the hepatic nuclear factor (HNF) family as controllers of a network of genes affecting GGT. Our results reinforce the disease associations of GGT and demonstrate that control by the GGT1 locus varies with age.

A twin-sibling study on the relationship between exercise attitudes and exercise behavior.

Social cognitive models of health behavior propose that individual differences in leisure time exercise behavior are influenced by the attitudes towards exercise. At the same time, large scale twin-family studies show a significant influence of genetic factors on regular exercise behavior. This twin-sibling study aimed to unite these findings by demonstrating that exercise attitudes can be heritable themselves. Secondly, the genetic and environmental cross-trait correlations and the monozygotic (MZ) twin intrapair differences model were used to test whether the association between exercise attitudes and exercise behavior can be causal. Survey data were obtained from 5,095 twins and siblings (18-50 years). A genetic contribution was found for exercise behavior (50 % in males, 43 % in females) and for the six exercise attitude components derived from principal component analysis: perceived benefits (21, 27 %), lack of skills, support and/or resources (45, 48 %), time constraints (25, 30 %), lack of energy (34, 44 %), lack of enjoyment (47, 44 %), and embarrassment (42, 49 %). These components were predictive of leisure time exercise behavior (R(2) = 28 %). Bivariate modeling further showed that all the genetic (0.36 < |rA| < 0.80) and all but two unique environmental (0.00 < |rE| < 0.27) correlations between exercise attitudes and exercise behavior were significantly different from zero, which is a necessary condition for the existence of a causal effect driving the association. The correlations between the MZ twins' difference scores were in line with this finding. It is concluded that exercise attitudes and exercise behavior are heritable, that attitudes and behavior are partly correlated through pleiotropic genetic effects, but that the data are compatible with a causal association between exercise attitudes and behavior.

Harmonization of Neuroticism and Extraversion phenotypes across inventories and cohorts in the Genetics of Personality Consortium: an application of Item Response Theory.

Mega- or meta-analytic studies (e.g. genome-wide association studies) are increasingly used in behavior genetics. An issue in such studies is that phenotypes are often measured by different instruments across study cohorts, requiring harmonization of measures so that more powerful fixed effect meta-analyses can be employed. Within the Genetics of Personality Consortium, we demonstrate for two clinically relevant personality traits, Neuroticism and Extraversion, how Item-Response Theory (IRT) can be applied to map item data from different inventories to the same underlying constructs. Personality item data were analyzed in >160,000 individuals from 23 cohorts across Europe, USA and Australia in which Neuroticism and Extraversion were assessed by nine different personality inventories. Results showed that harmonization was very successful for most personality inventories and moderately successful for some. Neuroticism and Extraversion inventories were largely measurement invariant across cohorts, in particular when comparing cohorts from countries where the same language is spoken. The IRT-based scores for Neuroticism and Extraversion were heritable (48 and 49 %, respectively, based on a meta-analysis of six twin cohorts, total N = 29,496 and 29,501 twin pairs, respectively) with a significant part of the heritability due to non-additive genetic factors. For Extraversion, these genetic factors qualitatively differ across sexes. We showed that our IRT method can lead to a large increase in sample size and therefore statistical power. The IRT approach may be applied to any mega- or meta-analytic study in which item-based behavioral measures need to be harmonized.

The genetic architecture of liver enzyme levels: GGT, ALT and AST.

High levels of liver enzymes GGT, ALT and AST are predictive of disease and all-cause mortality and can reflect liver injury, fatty liver and/or oxidative stress. Variation in GGT, ALT and AST levels is heritable. Moderation of the heritability of these liver enzymes by age and sex has not often been explored, and it is not clear to what extent non-additive genetic and shared environmental factors may play a role. To examine the genetic architecture of GGT, ALT and AST, plasma levels were assessed in a large sample of twins, their siblings, parents and spouses (N = 8,371; age range 18-90). For GGT and ALT, but not for AST, genetic structural equation modeling showed evidence for quantitative sex differences in the genetic architecture. There was no evidence for qualitative sex differences, i.e. the same genes were expressed in males and females. Both additive and non-additive genetic factors were important for GGT in females (total heritability h(2) 60 %) and AST in both sexes (total h(2) 43 %). The heritability of GGT in males and ALT for both sexes was due to additive effects only (GGT males 30 %; ALT males 40 %, females 22 %). Evidence emerged for shared environmental factors influencing GGT in the male offspring generation (variance explained 28 %). Thus, the same genes influence liver enzyme levels across sex and age, but their relative contribution to the variation in GGT and ALT differs in males and females and for GGT across age. Given adequate sample sizes these results suggest that genome-wide association studies may result in the detection of new susceptibility loci for liver enzyme levels when pooling results over sex and age.

The Adult Netherlands Twin Register: twenty-five years of survey and biological data collection.

Over the past 25 years, the Adult Netherlands Twin Register (ANTR) has collected a wealth of information on physical and mental health, lifestyle, and personality in adolescents and adults. This article provides an overview of the sources of information available, the main research findings, and an outlook for the future. Between 1991 and 2012, longitudinal surveys were completed by twins, their parents, siblings, spouses, and offspring. Data are available for 33,957 participants, with most individuals having completed two or more surveys. Smaller projects provided in-depth phenotyping, including measurements of the autonomic nervous system, neurocognitive function, and brain imaging. For 46% of the ANTR participants, DNA samples are available and whole genome scans have been obtained in more than 11,000 individuals. These data have resulted in numerous studies on heritability, gene x environment interactions, and causality, as well as gene finding studies. In the future, these studies will continue with collection of additional phenotypes, such as metabolomic and telomere length data, and detailed genetic information provided by DNA and RNA sequencing. Record linkage to national registers will allow the study of morbidity and mortality, thus providing insight into the development of health, lifestyle, and behavior across the lifespan.

Corrigendum: Longitudinal relations between parenting stress and child internalizing and externalizing behaviors: testing within-person changes, bidirectionality and mediating mechanisms.

[This corrects the article DOI: 10.3389/fnbeh.2022.942363.].

Thought problems from adolescence to adulthood: measurement invariance and longitudinal heritability.

This study investigates the longitudinal heritability in Thought Problems (TP) as measured with ten items from the Adult Self Report (ASR). There were ~9,000 twins, ~2,000 siblings and ~3,000 additional family members who participated in the study and who are registered at the Netherlands Twin Register. First an exploratory factor analysis was conducted to examine the underlying factor structure of the TP-scale. Then the TP-scale was tested for measurement invariance (MI) across age and sex. Next, genetic and environmental influences were modeled on the longitudinal development of TP across three age groups (12-18, 19-27 and 28-59 year olds) based on the twin and sibling relationships in the data. An exploratory factor analysis yielded a one-factor solution, and MI analyses indicated that the same TP-construct is assessed across age and sex. Two additive genetic components influenced TP across age: the first influencing TP throughout all age groups, while the second arises during young adulthood and stays significant throughout adulthood. The additive genetic components explained 37% of the variation across all age groups. The remaining variance (63%) was explained by unique environmental influences. The longitudinal phenotypic correlation between these age groups was entirely explained by the additive genetic components. We conclude that the TP-scale measures a single underlying construct across sex and different ages. These symptoms are significantly influenced by additive genetic factors from adolescence to late adulthood.

Stable genetic effects on symptoms of alcohol abuse and dependence from adolescence into early adulthood.

Relatively little is known about how genetic influences on alcohol abuse and dependence (AAD) change with age. We examined the change in influence of genetic and environmental factors which explain symptoms of AAD from adolescence into early adulthood. Symptoms of AAD were assessed using the four AAD screening questions of the CAGE inventory. Data were obtained up to six times by self-report questionnaires for 8,398 twins from the Netherlands Twin Register aged between 15 and 32 years. Longitudinal genetic simplex modeling was performed with Mx. Results showed that shared environmental influences were present for age 15-17 (57%) and age 18-20 (18%). Unique environmental influences gained importance over time, contributing 15% of the variance at age 15-17 and 48% at age 30-32. At younger ages, unique environmental influences were largely age-specific, while at later ages, age-specific influences became less important. Genetic influences on AAD symptoms over age could be accounted for by one factor, with the relative influence of this factor differing across ages. Genetic influences increased from 28% at age 15-17 to 58% at age 21-23 and remained high in magnitude thereafter. These results are in line with a developmentally stable hypothesis that predicts that a single set of genetic risk factors acts on symptoms of AAD from adolescence into young adulthood.

Longevity candidate genes and their association with personality traits in the elderly.

Human longevity and personality traits are both heritable and are consistently linked at the phenotypic level. We test the hypothesis that candidate genes influencing longevity in lower organisms are associated with variance in the five major dimensions of human personality (measured by the NEO-FFI and IPIP inventories) plus related mood states of anxiety and depression. Seventy single nucleotide polymorphisms (SNPs) in six brain expressed, longevity candidate genes (AFG3L2, FRAP1, MAT1A, MAT2A, SYNJ1, and SYNJ2) were typed in over 1,000 70-year old participants from the Lothian Birth Cohort of 1936 (LBC1936). No SNPs were associated with the personality and psychological distress traits at a Bonferroni corrected level of significance (P < 0.0002), but there was an over-representation of nominally significant (P < 0.05) SNPs in the synaptojanin-2 (SYNJ2) gene associated with agreeableness and symptoms of depression. Eight SNPs which showed nominally significant association across personality measurement instruments were tested in an extremely large replication sample of 17,106 participants. SNP rs350292, in SYNJ2, was significant: the minor allele was associated with an average decrease in NEO agreeableness scale scores of 0.25 points, and 0.67 points in the restricted analysis of elderly cohorts (most aged >60 years). Because we selected a specific set of longevity genes based on functional genomics findings, further research on other longevity gene candidates is warranted to discover whether they are relevant candidates for personality and psychological distress traits.

Longitudinal relations between parenting stress and child internalizing and externalizing behaviors: Testing within-person changes, bidirectionality and mediating mechanisms.

Introduction: Parenthood can be experienced as a pleasant but challenging period for parents, possibly accompanied by parenting stress. Early parenthood in particular is a vulnerable period as many parents experience biological and psychosocial changes related to new parenthood. Previous studies have shown that parenting stress is related to child behavior problems, but few studies have investigated the transactional relations across time between parenting stress and child internalizing and externalizing outcomes separately, examining within-person changes. The first aim of this study was to examine the transactional within-person associations of parenting stress and child internalizing and externalizing behavior problems across childhood from age 9 months to 9 years. As a second aim, we examined parenting as a possible underlying mechanism of the transactional associations by testing whether parental warmth and hostility mediate within-person associations of parenting stress and child behavior across time. Method: Data were analyzed from the Growing Up in Ireland longitudinal child cohort study including 7,208 caregiver-child dyads at wave 1 (child's age 9 months), who were followed at child's age three (wave 2), five (wave 3), and 9 years (wave 5). Primary caregiver's and child's age and gender, household income, occupational status, educational status, partner status, and cultural background were covariates assessed at all waves. Data were analyzed using a random intercept cross-lagged panel model (CLPM) in R-lavaan. Results: Bidirectional relations between parenting stress and child behavior were found for both internalizing and externalizing behavior from age 5 to 9, but not for earlier time points. Discussion: Our results did not indicate mediating effects of parental warmth or parental hostility in the associations between parenting stress and child behavior problems. Therefore, we conclude that parenting stress and child internalizing as well as parenting stress and child externalizing behaviors have transactional associations from child's age 5 to 9 years. Future research examining transactional associations of parenting stress and child behaviors should investigate possible other mediations taking a within-person approach by utilizing the RI-CLPM.

The effects of oxytocin and vasopressin administration on fathers' neural responses to infant crying: A randomized controlled within-subject study.

In a randomized double-blind within-subject control study we investigated the effects of oxytocin and vasopressin administration on neural reactivity to infant cry sounds in 70 first-time fathers in the first year of fatherhood. Additionally, we examined whether effects of oxytocin and vasopressin administration on neural reactivity were moderated by fathers' early childhood experiences. Neural reactivity to infant cry sounds (versus control sounds) was measured using functional magnetic resonance imaging (fMRI). Furthermore, participants reported on their childhood experiences of parental harsh discipline and parental love withdrawal. Whole brain analyses revealed no significant effect of vasopressin or oxytocin administration on neural activation in response to infant cry sounds. Region of interest analyses showed decreased amygdala activation in both the oxytocin condition and the vasopressin condition as compared to placebo. We found no moderating effects of fathers' early childhood experiences. Our findings suggest that oxytocin administration may decrease feelings of anxiety or aversion to a crying infant. Whether decreased amygdala activation after vasopressin administration might be explained by contextual factors (e.g., absence of high levels of threat, unfamiliarity of the infant) or represents an affiliative response to infant distress warrants further investigation. Findings of the present study showed that oxytocin and vasopressin are important hormones implicated in neural models of infant cry perception in fatherhood.

Exercise participation in adolescents and their parents: evidence for genetic and generation specific environmental effects.

Individual differences in adolescent exercise behavior are to a large extent explained by shared environmental factors. The aim of this study was to explore to what extent this shared environment represents effects of cultural transmission of parents to their offspring, generation specific environmental effects or assortative mating. Survey data on leisure-time exercise behavior were available from 3,525 adolescent twins and their siblings (13-18 years) and 3,138 parents from 1,736 families registered at the Netherlands Twin Registry. Data were also available from 5,471 adult twins, their siblings and spouses similar in age to the parents. Exercise participation (No/Yes, using a cut-off criterion of 4 metabolic equivalents and 60 min weekly) was based on questions on type, frequency and duration of exercise. A model to analyze dichotomous data from twins, siblings and parents including differences in variance decomposition across sex and generation was developed. Data from adult twins and their spouses were used to investigate the causes of assortative mating (correlation between spouses = 0.41, due to phenotypic assortment). The heritability of exercise in the adult generation was estimated at 42%. The shared environment for exercise behavior in adolescents mainly represents generation specific shared environmental influences that seem somewhat more important in explaining familial clustering in girls than in boys (52 versus 41%). A small effect of vertical cultural transmission was found for boys only (3%). The remaining familial clustering for exercise behavior was explained by additive genetic factors (42% in boys and 36% in girls). Future studies on adolescent exercise behavior should focus on identification of the generation specific environmental factors.

Variance components models for physical activity with age as modifier: a comparative twin study in seven countries.

Physical activity is influenced by genetic factors whose expression may change with age. We employed an extension to the classical twin model that allows a modifier variable, age, to interact with the effects of the latent genetic and environmental factors. The model was applied to self-reported data from twins aged 19 to 50 from seven countries that collaborated in the GenomEUtwin project: Australia, Denmark, Finland, Norway, Netherlands, Sweden and United Kingdom. Results confirmed the importance of genetic influences on physical activity in all countries and showed an age-related decrease in heritability for 4 countries. In the other three countries age did not interact with heritability but those samples were smaller or had a more restricted age range. Effects of shared environment were absent, except in older Swedish participants. The study confirms the importance of taking age effects into account when exploring the genetic and environmental contribution to physical activity. It also suggests that the power of genome-wide association studies to identify the genetic variants contributing to physical activity may be larger in young adult cohorts.