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Intergenerational effects--a review of environmentally oriented studies concerning the relationship between parental alcohol problems and family disharmony in the genesis of alcohol and other problems. I: The intergenerational effects of alcohol problems.

This paper is the first in a two-part series. In this paper the literature on the intergenerational transmission of alcohol problems is reviewed from an environmental perspective. It is concluded that there are effects of problem drinking on children, but that the long-term effects of parental problem drinking on the offspring once they reach adulthood are not so well documented. It is suggested that whether or not intergenerational continuities are found depends largely upon the source of the sample, that very little is known about adulthood outcomes other than drinking status, and that there is a striking sex bias in the literature, with most research examining the effects of problem-drinking fathers upon their male offspring. Possible mechanisms whereby parental problem drinking could affect adjustment are outlined and discussed. The notion of disturbed family relationships acting as a possible mediator for the transmission of problems is raised.

Adolescent

Intergenerational effects--a review of environmentally oriented studies concerning the relationship between parental alcohol problems and family disharmony in the genesis of alcohol and other problems. II: The intergenerational effects of family disharmony.

This paper is the second in a two-part series. In this paper the literature on the intergenerational transmission of family disharmony is reviewed from an environmental perspective. It is concluded that there is considerable evidence that children who grow up in a home which has a discordant atmosphere are at higher risk of developing a number of childhood problems and disorders than are comparison children. It is also clear that particularly likely outcomes for boys are antisocial behavior patterns and conduct disorder. The evidence also suggests that adults raised in a discordant atmosphere are still at high risk of developing a variety of problems once they reach adulthood. It is suggested that the negative effects of having a problem-drinking parent are mediated via family disharmony, and that in the absence of such disharmony the offspring will not be damaged. Suggestions are made for further research.

Adolescent

Intergenerational effects of the Holocaust: patterns of engagement in the mother-daughter relationship.

The present study explored the quality of engagement between mothers and adult daughters. Daughters of Holocaust survivors, European immigrants, and nonimmigrants were compared on mothers' protectiveness and care during their daughters' first 16 years, and on daughters' individuation from the family of origin. The survivor group perceived themselves as less individuated from both their parents than the other two groups. However, daughters in the three groups reported feeling equally intimate with their parents. There were no significant group differences found on intergenerational intimidation or competing loyalties. There was a tendency for mothers in the survivor group to be perceived as more indulgently protective. These findings suggest that the relationship between survivor mothers and their daughters may be characterized by a lower degree of individuation, though not at the cost of intimacy.

Adaptation, Psychological

Mediators of the Association Between a Parent's Experience of Trauma and Their Children's Well-Being: A Systematic Review.

At present, our understanding of trauma's complexity is underdeveloped, particularly with regard to intergenerational effects. In this paper, we review peer-reviewed literature on parental trauma and child well-being, focusing on mediating factors. We conducted a global systematic review of longitudinal, observational studies assessing mediators between a parent's traumatic exposure and their children's well-being. The primary outcome of the review was quantitative measures of child well-being (physical and psycho-social) assessed when the child was 18 years or under. We considered the following experiences as trauma exposures: intimate partner violence, rape, sexual assault, victimization during violent crime, childhood abuse, and exposure to direct, immediate threats to personal survival during war, political unrest, natural disasters, and sudden, critical injury/illness. Thirty-two studies met our inclusion criteria. The two most common mediator categories were caregiver mental health (n = 13) and parenting behavior (n = 10). Other studies measured aspects of the parent-child relationship (n = 9), maternal stress factors (n = 5), parental physical health (n = 2), and child-level factors (n = 6) as mediators. Almost all included studies (n = 28) detected a mediation effect. The majority of studies (n = 21) cited robust theoretical frameworks to support their mediator and outcome choices. Studies varied in quality, but most used appropriate, formal mediation analyses. Several study designs could be enhanced by methods to improve precision and reduce bias. Currently, there is little consistency in how similar constructs are measured between mediation studies. We did not locate any studies in low-income countries, and few studies examined aspects of family dynamics, physical health, environmental characteristics, or paternal factors.

Humans

The effects of intergenerational experiences on adolescents and older adults.

We evaluated an intergenerational program bringing together older people and adolescents to examine assumptions underlying intergenerational programming and determine if either generation changed its attitudes toward the other. Program components allowed older people and adolescents to act as either intergenerational helpers or recipients of help. The amount of intergenerational contact prior to participating in the program was examined. Only one group's attitudes changed following participation in the program: adolescents who helped older people showed more enjoyment in being with older people, decreased social distance, and a more positive perception of older people's attitudes toward the young.

Adolescent

The contrasting effects of parental birthweight and gestational age on the birthweight of offspring.

Investigations on intergenerational effects on birthweight have been carried out using the data of the 1958 British National Birthday Trust Fund cohort and its follow-up to 23 years, the National Child Development Study (NCDS-4), which included information on all births to cohort members by that age. This report is directed particularly at ascertaining the independent effect of parental gestational age on babies' birthweight. The two main findings are a direct association between parental and offspring birthweight (significant for both mothers and fathers after allowing for confounding factors), but an inverse association with parental gestational age (significant only for the mothers). It is postulated that at least part of this effect is mediated through the association between maternal fetal growth rate and their babies' birthweight; the faster the rate the shorter the gestational age for a given birthweight. It was not possible to ascertain what part genetic factors played in this relationship. Larger and more informative intergenerational studies are needed to further knowledge on this question.

Adult

Parental height: childhood environment and subsequent adult height in a national birth cohort.

Low parental social class was associated with shorter adult stature in offspring in a national birth cohort. Since short adult stature is a risk factor for serious illness, particularly heart disease, origins of the observed class differences were sought in the childhood environment and in combined genetic and environmental factors represented by midparent height and birthweight. In addition to social class the childhood environmental factors of birth order, number of surviving younger siblings, overcrowding and mother's education were found to be significant and independent predictors of adult height, even after adjusting for parental heights and birthweight, and had therefore a long-term intragenerational effect. Both midparent height and birthweight constitute a combination of environmental and genetic influences, and therefore to some extent are an intergenerational effect. Improvements in environmental factors are thus likely to reduce social variation in adult height for both intra and intergenerational reasons.

Body Height

Cardiovascular risk factors in a French Canadian population: resolution of genetic and familial environmental effects on blood pressure using twins, adoptees, and extensive information on environmental correlates.

Genetic and environmental influences on systolic (SBP), diastolic (DBP), and mean arterial (MBP) blood pressure were examined using an expanded version of a path model in which parents and their singleton, twin, and adopted offspring were incorporated, and which also included an environmental index as an estimate of the underlying familial environmental component. Estimates of genetic heritability are lower in parents (10-15%) than in offspring (40-50%). Cultural heritability was significant for SBP (0.31) and MBP (0.40), and an intergenerational effect was found for DBP, with higher estimates in parents (0.42) than in offspring (0.21). Marital resemblance was significant, and no support was found for differential maternal and paternal cultural transmission. Two novel results arising from this study are 1) gender-specific sibling effects, with greater female than male resemblance for SBP and MBP and the opposite pattern for DBP, and 2) the suggestion of extra twin resemblance arising on account of additional shared environments and resulting in greater like-sex than opposite-sex twin resemblance. The major conclusions drawn from this study are that 1) parameter estimates are stable with or without the use of extensive environmental indices, and 2) the addition of twins and adoptees did not significantly impact the results, with the exception of a possible influence of the adoptees in estimates of cultural heritability for DBP. Combining both these features (i.e., extended relatives and environmental indices) enables testing for additional sources of familial aggregation, which is not possible using the traditional nuclear family approach and results in a more accurate assessment of the relative roles of heredity and environment on blood pressure than has been previously possible.

Adolescent

Resolution of genetic and cultural inheritance in twin families by path analysis: application to HDL-cholesterol.

A path model and associated statistical method for the analysis of data on twin families are introduced and applied to high density lipoprotein cholesterol (HDL-c) observations in the Swedish Twin Family Study. The proposed path model incorporates both genetic and environmental sources of familial resemblance, maternal environmental effects, intergenerational differences in heritabilities, marital resemblance due to either primary or secondary phenotypic homogamy, and twin residual environmental correlations. Application of the model to HDL-c levels resulted in parameter estimates consistent with those reported in earlier reviews and in the analysis of nuclear family and twin data. Genetic heritability was estimated as h2 = .363 +/- .243, cultural heritability as c2 = .187 +/- .082, and the proportion of phenotypic variance due to residual environmental effects as r2 = .450 +/- .207. Although the parameter estimates were comparable, the statistical tests of hypotheses were, relative to other designs, of low statistical power. It appears that environmental indices are necessary for powerful tests of hypotheses.

Analysis of Variance

Contribution of the Brain-Gut-Microbiome Axis to Intergenerational Abnormalities in a Rat Model of Perioperative Neurocognitive Disorder.

BACKGROUND: The brain-gut-microbiome (BGM) axis is a communication network through which the brain and gastrointestinal microbiota interact via neural, hormonal, immune, and gene expression mechanisms. Gut microbiota dysbiosis is thought to contribute to neurocognitive disorders, including perioperative neurocognitive disorder, and to various metabolic abnormalities. Recently, the authors reported that sevoflurane induces neurocognitive deficits in exposed rats as well as their future offspring, with male offspring being particularly affected (intergenerational perioperative neurocognitive disorder). In this study, the authors examined in the same animals whether the intergenerational effects of sevoflurane involve abnormalities in the BGM axis, and whether they are mitigated by paternal pretreatment with either the Na + -K + -Cl - (NKCC1) Cl - transporter inhibitor bumetanide or the glucocorticoid receptor inhibitor RU486, as previously demonstrated for neurocognitive deficits. METHODS: Male Sprague-Dawley rats (F0 generation) were exposed to 2.1% sevoflurane for 3 h on postnatal days 56, 58, and 60 (F0M_S group). Before each sevoflurane exposure, distinct experimental groups of F0 males received bumetanide (F0M_BS group) or RU486 (F0M_RS group). These males were mated on postnatal day 90 to produce offspring (F1 generation). Gut microbiota were profiled using 16S rRNA gene sequencing, and brain changes analyzed via RNA sequencing of hippocampal samples. RESULTS: F1 male offspring of F0M_S sires exhibited heightened corticosterone responses to stress, increased inflammatory markers, altered hippocampal transcriptomes, gut microbiota dysbiosis, elevated serum low-density lipoprotein cholesterol levels, and increased body weight. The only abnormality observed in F1 females was a shift in microbial diversity. F0M_S displayed profound alterations in hippocampal transcriptome, while microbial diversity was the only parameter affected in their gut microbiota. Bumetanide or RU486 mitigated most abnormalities, except increased body weight in F1 males. CONCLUSIONS: Paternal sevoflurane exposure in rats induces BGM axis abnormalities, particularly in male offspring, despite the absence of direct anesthetic exposure. Pretreatment with bumetanide or RU486 showed therapeutic efficacy.

Animals

Family structure and dependency: early transitions to female household headship.

This article looks at the intergenerational effects of family structure on family formation and economic dependency. Three explanations are examined: the economic-deprivation, socialization, and family-stress hypotheses. Daughters living in single-parent families at some point during adolescence are more likely to become household heads and to go on welfare than offspring of two-parent families. Differences in the incomes of one- and two-parent families can account for up to 25 percent of the difference in offspring behaviors. None of the hypotheses, however, provides a complete explanation of family structure effects. The analysis is based on data from the Panel Study of Income Dynamics and uses event-history analysis to estimate transitions into female headship and economic dependence.

Adolescent

Social mobility and hypertension among blacks.

This paper considers the role of social mobility to hypertension among blacks. Using a nationally representative sample of the adult black population, this research finds no effects of intergenerational socioeconomic mobility. Minimal effects are found for geographic mobility; geographic moves bears a small positive relationship to hypertension. The implications for a theory of mobility effects on black health are discussed.

Adult

Family size in successive generations: the effects of birth order, intergenerational change in lifestyle, and familial satisfaction.

Studies of family size in successive generations have found a small but persistently positive effect of size of family of orientation. Recent work has suggested that this relationship may be influenced by birth order, intergenerational change in lifestyle, and familial satisfaction. Data from a 24-year longitudinal study of women in Pennsylvania indicate that number of siblings does influence size of family of procreation. More important, this relationship is stronger among women who were first-born that later-born, stronger for those not experiencing intergenerational change than for those who changed, and stronger among those who at age 16 were satisfied with their parental family than for those who were dissatisfied.

Adult

Home orientation in nursling rats: the effects of rehabilitation following intergenerational malnutrition.

Rat pups with histories of intergenerational malnutrition were rehabilitated by cross-fostering at birth to well-nourished females. These pups weighed slightly less than well-nourished controls but significantly more than pups reared by malnourished females. Rehabilitated and control pups were both more active than malnourished pups reared by malnourished females. However, the percentage of nest returns by pups displaced to other parts of the cage was low among rehabilitated pups as compared with controls, but did not differ from that of pups with histories of intergenerational malnutrition reared by malnourished females. These data suggest that, although activity is a product of postnatal condition, home-orienting behavior is affected by a history of intergenerational malnutrition regardless of rehabilitation.

Animal Population Groups

Genetic and environmental determinants of periodontal disease.

Reanalysis of data on periodontal disease in 241 families [Chung et al, 1977b], based on an extended and more satisfactory path model [Rao et al, 1979], failed to detect significant heritability, and concluded in favor of cultural inheritance only, without maternal effects or intergenerational differences. The most parsimonious hypothesis yields a relative variance component of 0.338 +/- 0.024 due to indexed environment for both children and adults, the remainder (1.0--0.338 = 0.662) being due to residual nongenetic factors.

Culture

Paternal exposure to polystyrene nanoplastics induces inter- and transgenerational bronchopulmonary dysplasia-like damage in male offspring by FtMt hypermethylation-mediated ferroptosis.

Bronchopulmonary dysplasia (BPD) is a major cause of chronic lung disease in both preterm infants and adults, but its etiology remains incompletely understood. In this study, F0 generation mice were exposed to polystyrene nanoplastics (PS-NPs), and F1 to F3 generations were obtained by breeding. Multi-omics sequencing including whole genome methylation sequencing, single cell transcriptome sequencing and transcriptome sequencing was performed on the lungs of offspring. The levels of Fe2+, lipid peroxidation products and key gene expression were determined. Male mice exposed to PS-NPs at environmentally relevant doses produced offspring (F1 and F2) that exhibited a typical BPD-like phenotype. Meanwhile, the F0 males showed diminished sperm motility, demonstrating that paternal PS-NPs exposure constituted an etiological factor for BPD in descendants. Mechanistic studies showed that PS-NPs exposure upregulated the expression of DNA methyltransferase Dnmt3a, leading to global hypermethylation of the sperm genome. Importantly, the hypermethylated promoter signature of the mitochondrial ferritin (FtMt) gene partially resisted epigenetic reprogramming and was transmitted to the lungs of offspring, resulting in persistently low FtMt expression in F1 and F2 lungs. This led to increased intracellular Fe2+ levels, subsequently triggered ferroptosis in alveolar epithelial cells, and ultimately impaired alveolarization. Knockdown of FtMt confirmed that FtMt deficiency was sufficient to induce ferroptosis and BPD-like lung injury both in vitro and in vivo. Furthermore, using in vitro fertilization of F0 sperm combined with Dnmt3a siRNA microinjection, we directly demonstrated that Dnmt3a is a key driver for FtMt to escape reprogramming and maintain its hypermethylation. In summary, this study reveals for the first time that paternal PS-NPs exposure causes BPD through a Dnmt3a-FtMt hypermethylation intergenerational and transgenerational axis, providing an epigenetic basis for understanding paternal derived chronic lung disease and potential targets for early intervention.

Animals

Heterogeneity in the familial aggregation of fasting plasma glucose in five North American populations: the Lipid Research Clinics Family Study.

Heterogeneity in the familial aggregation of plasma glucose in five samples of the Lipid Research Clinics Family Study (LRC) was investigated using path analysis. This study was deemed appropriate since recent investigations reported a wide range of estimates for genetic and cultural factors. The path model incorporated a measured index of the familial environment in order to separate the effects of genes and environments in the nuclear family design, genetic and environmental heritabilities, spouse resemblance, sibling environmental effects, and parental cultural transmission. The methodology was completely general in allowing sample-specific, as well as pooled-sample, estimation of all or any subset of the model parameters. Genetic heritability estimates were heterogeneous, ranging from zero to 33% across the clinics. Environmental heritability (7%), spouse resemblance, non-transmitted sibling environmental effects, and parental cultural transmission were homogeneous across samples. No support was found for specific maternal effects, nor for intergenerational differences in cultural or genetic heritability. We conclude that the genetic and environmental heritabilities for plasma glucose in the LRC are consistent with the diverse reports by earlier investigators. In addition, we were able to exclude methodological differences as a cause of this heterogeneity. Furthermore, formal hypothesis tests suggest that the aetiology of this heterogeneity is genetic (and not cultural), taking the form of two distinct homogeneous patterns (one for no genetic effect, and one for a moderate genetic effect). Only formal heterogeneity tests of the type described here can detect these effects, and allow pooling of separate studies in order to obtain more precise estimates of the parameters of interest.

Adult