Maternal history of maltreatment and offspring's emotional and behavioral problems in adolescence: Do family factors contribute to the intergenerational risk transmission?

BACKGROUND: A history of childhood maltreatment often has a negative and long-lasting impact across different domains in life. A childhood maltreatment experience in parents may even affect the next generation. So far, the effects of family factors have been considered in the intergenerational transmission of adversity across the childhood years, but whether the effects remain until adolescence is less clear. OBJECTIVE: Using data from a large population-based study in the Netherlands, including both mother and child reports, we examined whether maternal childhood maltreatment history is associated with increased mental health problems in offspring and the role of family functioning and harsh parenting as a potential pathway. PARTICIPANTS: 4912 adolescents (aged 13 years) and their mothers were recruited in the Generation R study. METHODS: Mothers reported childhood maltreatment experiences using the Childhood Trauma Questionnaire (CTQ), and adolescents reported on their mental health using the Youth Self Report (YSR). Structural equation modeling (SEM) was used to test the association of maternal childhood maltreatment on mental health problems in offspring and family functioning and harsh parenting as mechanisms to explain this association. RESULTS: Adolescents of mothers with a history of maltreatment had greater internalizing (ß = 0.07, p < .01) and externalizing problems (ß = 0.08, p < .01). Moreover, we found an indirect effect via family functioning over time and harsh parenting at ages 3 and 8 years which mediated this association. CONCLUSION: We concluded an intergenerational effect of maternal childhood maltreatment on adolescents internalizing and externalizing problems. The findings might enable earlier intervention within the family context to mitigate the consequences of maternal childhood maltreatment.

Gender Diversity and Brain Morphology Among Adolescents.

Importance: Gender-diverse youths have higher rates of mental health problems compared with the general population, as shown in both clinical and nonclinical populations. Brain correlates of gender diversity, however, have been reported only among youths with gender dysphoria or in transgender individuals. Objective: To examine brain morphologic correlates of gender diversity among adolescents from a general pediatric population who were assigned male or female at birth, separately. Design, Setting, and Participants: This cross-sectional study was embedded in Generation R, a multiethnic population-based study conducted in Rotterdam, the Netherlands. Adolescents who were born between April 1, 2002, and January 31, 2006, and had information on self-reported or parent-reported gender diversity and structural neuroimaging at ages 13 to 15 years were included. Data analysis was performed from April 1 to July 31, 2022. Exposures: Gender-diverse experiences among adolescents were measured with selected items from the Achenbach System of Empirically Based Assessment forms and the Gender Identity/Gender Dysphoria Questionnaire for Adolescents and Adults, as reported by adolescents and/or their parents. Main Outcomes and Measures: High-resolution structural neuroimaging data were collected using a 3-T magnetic resonance imaging scanner (at a single site). We used linear regression models to examine differences in global brain volumetric measures between adolescents who reported gender diversity and those who did not. Results: This study included 2165 participants, with a mean (SD) age of 13.8 (0.6) years at scanning. A total of 1159 participants (53.5%) were assigned female at birth and 1006 (46.5%) were assigned male at birth. With regard to maternal country of origin, 1217 mothers (57.6%) were from the Netherlands and 896 (42.4%) were from outside the Netherlands. Adolescents who reported gender diversity did not differ in global brain volumetric measures from adolescents who did not report gender diversity. In whole-brain, vertexwise analyses among adolescents assigned male at birth, thicker cortices in the left inferior temporal gyrus were observed among youths who reported gender diversity compared with those who did not. No associations were observed between gender diversity and surface area in vertexwise analyses. Conclusions and Relevance: The findings of this cross-sectional study suggest that global brain volumetric measures did not differ between adolescents who reported gender diversity and those who did not. However, these findings further suggest that gender diversity in the general population correlates with specific brain morphologic features in the inferior temporal gyrus among youths who are assigned male at birth. Replication of these findings is necessary to elucidate the potential neurobiological basis of gender diversity in the general population. Future longitudinal studies should also investigate the directionality of these associations.

Long-term associations between early-life family functioning and preadolescent white matter microstructure.

BACKGROUND: Causes of childhood behavior problems remain poorly understood. Enriched family environments and corresponding brain development may reduce the risk of their onset, but research investigating white matter neurodevelopmental pathways explaining associations between the family environment and behavior remains limited. We hypothesized that more positive prenatal and mid-childhood family functioning - a measure of a family's problem solving and supportive capacity - would be associated with two markers of preadolescent white matter neurodevelopment related to reduced behavior problems: higher global fractional anisotropy (FA) and lower global mean diffusivity (MD). METHODS: Data are from 2727 families in the Generation R Study, the Netherlands. Mothers reported family functioning (McMaster Family Assessment Device, range 1-4, higher scores indicate healthier functioning) prenatally and in mid-childhood (mean age 6.1 years). In preadolescence (mean age 10.1), the study collected diffusion-weighted scans. We computed standardized global MD and FA values by averaging metrics from 27 white matter tracts, and we fit linear models adjusting for possible confounders to examine global and tract-specific outcomes. RESULTS: Prenatal and mid-childhood family functioning scores were moderately correlated, r = 0.38. However, only prenatal family functioning - and not mid-childhood functioning - was associated with higher global FA and lower global MD in preadolescence in fully adjusted models: ßglobal FA = 0.11 (95% CI 0.00, 0.21) and ßglobal MD = -0.15 (95% CI -0.28, -0.03) per one-unit increase in functioning score. Sensitivity and tract-specific analyses supported these global findings. CONCLUSIONS: These results suggest high-functioning prenatal or perinatal family environments may confer lasting white matter neurodevelopmental benefits into preadolescence.

Childhood loneliness as a specific risk factor for adult psychiatric disorders.

BACKGROUND: Loneliness is a major risk factor for both psychological disturbance and poor health outcomes in adults. This study aimed to assess whether childhood loneliness is associated with a long-term disruption in mental health that extends into adulthood. METHODS: This study is based on the longitudinal, community-representative Great Smoky Mountains Study of 1420 participants. Participants were assessed with the structured Child and Adolescent Psychiatric Assessment interview up to eight times in childhood (ages 9-16; 6674 observations; 1993-2000) for childhood loneliness, associated psychiatric comorbidities and childhood adversities. Participants were followed up four times in adulthood (ages 19, 21, 25, and 30; 4556 observations of 1334 participants; 1999-2015) with the structured Young Adult Psychiatric Assessment Interview for psychiatric anxiety, depression, and substance use outcomes. RESULTS: Both self and parent-reported childhood loneliness were associated with adult self-reported anxiety and depressive outcomes. The associations remained significant when childhood adversities and psychiatric comorbidities were accounted for. There was no evidence for an association of childhood loneliness with adult substance use disorders. More associations were found between childhood loneliness and adult psychiatric symptoms than with adult diagnostic status. CONCLUSION: Childhood loneliness is associated with anxiety and depressive disorders in young adults, suggesting that loneliness - even in childhood - might have long-term costs in terms of mental health. This study underscores the importance of intervening early to prevent loneliness and its sequelae over time.

Double advantage of parental education for child educational achievement: the role of parenting and child intelligence.

BACKGROUND: Parental education is one of the best predictors of child school achievement. Higher parental education is not only associated with higher child intelligence, but children from highly educated parents also perform better in school due to other family related factors. This study evaluates the relation between parental education, child non-verbal intelligence and parenting practices with child school achievement. METHODS: Longitudinal data from a large population-based, multi-ethnic cohort of children in the Netherlands (63% Dutch origin) followed from birth to age 13 years (3547 children; 52.3% girls) were analyzed. School achievement was measured at the end of primary school (12 years of age) with a national Dutch academic test score. Parental education was assessed at age 3 years. The non-verbal intelligence of the child was measured at age 6 years and a full intelligence was measured at age 13 years. Maternal and paternal family routines, harsh parenting and corporal punishment were assessed in early and mid-childhood. Mediation analysis was performed with the G-formula and Structural Equation Models. RESULTS: Child intelligence partially mediated [B indirect effect =0.54 95% CI (0.46, 0.62) P < 0.001] the association between parental education and child school achievement. Independent of intelligence, family routines [B indirect effect =0.04 95% CI (0.01, 0.07) P < 0.01], but not harsh parenting mediated this association. CONCLUSIONS: Higher parental education was associated with better school achievement through two independent mechanisms, through higher intelligence of the child and parenting practices.

Association of Poor Family Functioning From Pregnancy Onward With Preadolescent Behavior and Subcortical Brain Development.

Importance: The association of poor family functioning, a potent stressor, with child behavior is potentially long term and relevant for a person's well-being later in life. Whether changes in brain development underlie the associations with preadolescent behavior and help identify periods of vulnerability is unclear. Objective: To assess the associations of poor family functioning from pregnancy onward with cortical, white matter, and subcortical volumes, and to examine the extent to which, in particular, hippocampal volume mediates the association of prenatal parental environmental exposures with child problem behavior in preadolescence. Design, Setting, and Participants: This population-based cohort study, conducted from April 2002 to January 2006, was embedded in Generation R, a multiethnic population-based cohort from fetal life onward. All pregnant women living in Rotterdam, the Netherlands, with an expected delivery date between April 2002 and January 2006 were invited to participate. Of the 8879 pregnant women enrolled during pregnancy, 1266 mothers with no partner data and 490 with missing family functioning data were excluded, as well as 1 sibling of 32 twin pairs. After excluding an additional 657 children with poor imaging data quality or incidental findings, the final sample consisted of 2583 mother-child pairs. Data analysis was performed from March 1, 2019, to June 28, 2019. Exposures: Mother- and father-rated poor family functioning was repeatedly measured by the General Functioning subscale of the Family Assessment Device. Main Outcomes and Measures: Our primary hypothesis, formulated after data collection but before analysis, was that poor prenatal family functioning would be associated with smaller hippocampal and amygdala volumes in late childhood. High-resolution structural neuroimaging data of children aged 10 years were collected with a single 3-T magnetic resonance imaging system. Child emotional and behavioral problems were assessed with the Child Behavior Checklist. Results: Data were available for 2583 children (mean [SD] age, 10.1 [0.6] years; 1315 girls [50.9%]). Data for parents included 2583 mothers (mean [SD] age, 31.1 [4.7] years; 1617 Dutch race/ethnicity [62.6%]) and 1788 fathers (mean [SD] age, 33.5 [5.3] years; 1239 Dutch race/ethnicity [69.3%]). Children exposed to prenatal maternal-reported poor family functioning had smaller hippocampal (B = -0.08; 95% CI, -0.13 to -0.02) and occipital lobe (B = -0.70; 95% CI, -1.19 to -0.21) volumes in preadolescence. There was no evidence for an association of exposure to poor family functioning at mid- or late childhood with brain morphology. Hippocampal volumes partially mediated the association of prenatal maternal-reported poor family functioning with preadolescent problem behavior (B = 0.08; 95% CI, 0.03-0.13), even after adjusting for prior child problems at age 1.5 years. Analyses of combined maternal and paternal family functioning ratings showed similar results, but associations were largely driven by maternal family functioning reports. Conclusions and Relevance: In this population-based cohort study, prenatal maternal-reported poor family functioning was associated with a smaller hippocampus in preadolescents. This difference in brain structure may underlie behavioral problems and is a possible neurodevelopmental manifestation of the long-term consequences of poor family functioning for the child.

From Parent to Child to Parent: Associations Between Parent and Offspring Psychopathology.

Parental psychopathology can affect child functioning, and vice versa. We examined bidirectional associations between parent and offspring psychopathology in 5,536 children and their parents. We asked three questions: (a) are parent-to-child associations stronger than child-to-parent associations? (b) are mother-to-child associations stronger than father-to-child associations? and (c) do within- and between-person effects contribute to bidirectional associations between parent and offspring psychopathology? Our findings suggest that only within-rater bidirectional associations of parent and offspring psychopathology can be consistently detected, with no difference between mothers and fathers. Child psychopathology was hardly associated with parental psychopathology. No evidence for cross-rater child-to-parent associations was found suggesting that the within-rater child-to-parent associations reflect shared method variance. Moreover, within-person change accounted for a part of the variance observed.

The Complex Role of Parental Separation in the Association between Family Conflict and Child Problem Behavior.

Parental separation is a major adverse childhood experience. Parental separation is generally preceded by conflict, which is itself a risk factor for child problem behavior. Whether parental separation independent of conflict has negative effects on child problem behavior is unclear. This study was embedded in Generation R, a population-based cohort followed from fetal life until age 9 years. Information on family conflict was obtained from 5,808 mothers and fathers. The 4-way decomposition method was used to apportion the effects of prenatal family conflict and parental separation on child problem behavior into 4 nonoverlapping components. Structural equation modeling was used to test bidirectional effects of child problem behavior and family conflict over time. Family conflict from pregnancy onward and parental separation each strongly predicted child problem behavior up to preadolescence according to maternal and paternal ratings. Using the 4-way decomposition method, we found evidence for a strong direct effect of prenatal family conflict on child problem behavior, for reference interaction, and for mediated interaction. The evidence for interaction implies that prenatal family conflict increased the children's vulnerability to the harmful effect of parental separation. There was no evidence of a pure indirect effect of parental separation on child problem behavior. Overall, results indicated that if parental separation occurs in families with low levels of conflict, parental separation does not predict more child problem behavior. Moreover, the bidirectional pattern suggested that child problem behavior influences the persistence of family conflict.

Polygenic Risk Scores for Developmental Disorders, Neuromotor Functioning During Infancy, and Autistic Traits in Childhood.

BACKGROUND: Impaired neuromotor development is often one of the earliest observations in children with autism spectrum disorder (ASD). We investigated whether a genetic predisposition to developmental disorders was associated with nonoptimal neuromotor development during infancy and examined the genetic correlation between nonoptimal neuromotor development and autistic traits in the general population. METHODS: In a population-based cohort in The Netherlands (2002-2006), we calculated polygenic risk scores (PRSs) for ASD and attention-deficit/hyperactivity disorder (ADHD) using genome-wide association study summary statistics. In 1921 children with genetic data, parents rated autistic traits at 6 years of age. Among them, 1174 children (61.1%) underwent neuromotor examinations (tone, responses, senses, and other observations) during infancy (9-20 weeks of age). We used linear regressions to examine associations of PRSs with neuromotor scores and autistic traits. We performed a bivariate genome-based restricted maximum likelihood analysis to explore whether genetic susceptibility underlies the association between neuromotor development and autistic traits. RESULTS: Higher PRSs for ASD were associated with less optimal overall infant neuromotor development, in particular low muscle tone. Higher PRSs for ADHD were associated with less optimal senses. PRSs for ASD and those for ADHD both were associated with autistic traits. The single nucleotide polymorphism-based heritability of overall motor development was 20% (SE = .21) and of autistic traits was 68% (SE = .26). The genetic correlation between overall motor development and autistic traits was .35 (SE = .21, p < .001). CONCLUSIONS: We found that genetic liabilities for ASD and ADHD covary with neuromotor development during infancy. Shared genetic liability might partly explain the association between nonoptimal neuromotor development during infancy and autistic traits in childhood.