The pernicious role of stress on intergenerational continuity of psychopathology.

Development and Psychopathology has been a premier resource for understanding stressful childhood experiences and the intergenerational continuity of psychopathology. Building on that tradition, we examined the unique and joint influences of maternal stress on children's effortful control (age 7) and externalizing behavior (age 11) as transmitted via genetics, the prenatal environment, and the postnatal environment. The sample included N = 561 adopted children and their biological and adoptive parents. Path models identified a direct effect of biological mother life stress on children's effortful control (ß = -.08) and an indirect effect of her life stress on child externalizing behavior via effortful control (ß = .52), but no main or indirect effects of biological parent psychopathology, prenatal stress, or adoptive mother adverse childhood experiences (ACES). Adoptive mother ACES amplified the association between biological mother life stress and child effortful control (ß = -.08), externalizing behavior (ß = 1.41), and the indirect effect via effortful control, strengthening associations when adoptive mothers reported average or high ACES during their own childhoods. Results suggest that novel study designs are needed to enhance the understanding of how life stress gets "under the skin" to affect psychopathology in the offspring of adults who have experienced stress.

Caregiver Perceived Stress and Child Sleep Health: An Item-Level Individual Participant Data Meta-Analysis.

Up to 50% of children and adolescents in the United States (U.S.) experience sleep problems. While existing research suggests that perceived stress in caregivers is associated with poorer sleep outcomes in children, research on this relationship is often limited to infant and early childhood populations; therefore, we investigated this association in school-age children and adolescents. We used cross-sectional caregiver-reported surveys and applied item response theory (IRT) followed by meta-analysis to assess the relationship between caregiver perceived stress and child sleep disturbance, and moderation of this relationship by child age and the presence of a child mental or physical health condition. We analyzed data from the National Institutes of Health (NIH) Environmental influences on Child Health Outcomes (ECHO) Program, a collaboration of existing pediatric longitudinal cohort studies that collectively contribute a diverse and large sample size ideal for addressing questions related to children's health and consolidating results across population studies. Participants included caregivers of children ages 8 to 16 years from four ECHO cohorts. Caregiver perceived stress was measured using the Perceived Stress Scale (PSS), and child sleep disturbance was assessed using five sleep-related items from the School-Age version of the Child Behavior Checklist (CBCL). Increases in caregiver perceived stress and child mental or physical health condition were independently associated with greater sleep disturbance among children. The findings reinforce the importance of accounting for, and potentially intervening on, the broader family context and children's mental and physical health in the interest of improving sleep health.

Using genetic designs to identify likely causal environmental contributions to psychopathology.

The multifactorial nature of psychopathology, whereby both genetic and environmental factors contribute risk, has long been established. In this paper, we provide an update on genetically informative designs that are utilized to disentangle genetic and environmental contributions to psychopathology. We provide a brief reminder of quantitative behavioral genetic research designs that have been used to identify potentially causal environmental processes, accounting for genetic contributions. We also provide an overview of recent molecular genetic approaches that utilize genome-wide association study data which are increasingly being applied to questions relevant to psychopathology research. While genetically informative designs typically have been applied to investigate the origins of psychopathology, we highlight how these approaches can also be used to elucidate potential causal environmental processes that contribute to developmental course and outcomes. We highlight the need to use genetically sensitive designs that align with intervention and prevention science efforts, by considering strengths-based environments to investigate how positive environments can mitigate risk and promote children's strengths.

Genetic Liabilities Differentiating Bipolar Disorder, Schizophrenia, and Major Depressive Disorder, and Phenotypic Heterogeneity in Bipolar Disorder.

Importance: Understanding the origins of clinical heterogeneity in bipolar disorder (BD) will inform new approaches to stratification and studies of underlying mechanisms. Objective: To identify components of genetic liability that are shared between BD, schizophrenia, and major depressive disorder (MDD) and those that differentiate each disorder from the others and to examine associations between heterogeneity for key BD symptoms and each component. Design, Setting, and Participants: Using data from the Bipolar Disorder Research Network in the United Kingdom, components of liability were identified by applying genomic structural equation modeling to genome-wide association studies of schizophrenia, BD, and MDD. Polygenic risk scores (PRS) representing each component were tested for association with symptoms in an independent BD data set. Adults with DSM-IV BD or schizoaffective disorder, bipolar type, were included. Data were collected from January 2000 to December 2013, and data were analyzed from June 2020 to February 2022. Main Outcomes and Measures: PRS representing the components of liability were tested for association with mania and depression, psychosis, and mood incongruence of psychosis in participants with BD, measured using the Bipolar Affective Disorder Dimensional Scale. Results: Of 4429 included participants, 3012 (68.0%) were female, and the mean (SD) age was 46.2 (12.3) years. Mania and psychosis were associated with the shared liability component (mania ß = 0.29; 95% CI, 0.23-0.34; P = 3.04 × 10-25; psychosis ß = 0.05; 95% CI, 0.04-0.07; P = 2.33 × 10-13) and the components that differentiate each of schizophrenia (mania ß = 0.08; 95% CI, 0.03-0.14; P = .002; psychosis ß = 0.03; 95% CI, 0.01-0.04; P = 1.0 × 10-4) and BD (mania ß = 0.14; 95% CI, 0.09-0.20; P = 1.99 × 10-7; psychosis ß = 0.02; 95% CI, 0.01-0.03; P = .006) from the other disorders. The BD differentiating component was associated with mania independently of effects on psychosis (ß = 0.14; 95% CI, 0.08-0.20; P = 4.32 × 10-6) but not with psychosis independently of mania. Conversely, the schizophrenia differentiating component was associated with psychosis independently of effects on mania (ß = 0.01; 95% CI, 0.003-0.03; P = .02), but not with mania independently of psychosis. Mood incongruence of psychosis was associated only with the schizophrenia differentiating component (ß = 0.03; 95% CI, 0.01-0.05; P = .005). Depression was associated with higher MDD differentiating component (ß = 0.07; 95% CI, 0.01-0.12; P = .01) but lower BD differentiating component (ß = -0.11; 95% CI, -0.17 to -0.06; P = 7.06 × 10-5). Conclusions and Relevance: In this study of BD, clinical heterogeneity reflected the burden of liability to BD and the contribution of alleles that have differentiating effects on risk for other disorders; mania, psychosis, and depression were associated with the components of genetic liability differentiating BD, MDD, and schizophrenia, respectively. Understanding the basis of this etiological heterogeneity will be critical for identifying the different pathophysiological processes underlying BD, stratifying patients, and developing precision therapeutics.

Developmental profiles of child behavior problems from 18 months to 8 years: The protective effects of structured parenting vary by genetic risk.

Some children are more affected by specific family environments than others, as a function of differences in their genetic make-up. However, longitudinal studies of genetic moderation of parenting effects during early childhood have not been conducted. We examined developmental profiles of child behavior problems between 18 months and age 8 in a longitudinal parent-offspring sample of 361 adopted children. In toddlerhood (18 months), observed structured parenting indexed parental guidance in service of task goals. Biological parent psychopathology served as an index of genetic influences on children's behavior problems. Four profiles of child behavior problems were identified: low stable (11%), average stable (50%), higher stable (29%), and high increasing (11%). A multinominal logistic regression analysis indicated a genetically moderated effect of structured parenting, such that for children whose biological mother had higher psychopathology, the odds of the child being in the low stable group increased as structured parenting increased. Conversely, for children whose biological mother had lower psychopathology, the odds of being in the low stable group was reduced when structured parenting increased. Results suggest that increasing structured parenting is an effective strategy for children at higher genetic risk for psychopathology, but may be detrimental for those at lower genetic risk.

The Potential of Children's Rearing Environment to Overcome Genetic Propensity for Low Reading Achievement.

Genetic studies show that children's reading achievement is in part genetically influenced, and intervention studies show that reading achievement can be increased by environmental interventions. However, correlational and mean-level analytic strategies are rarely integrated into achievement research, potentially leading to misinterpretation of results. The parent-offspring adoption design offers a novel opportunity to examine the independent and joint roles of genetic and rearing environmental contributions. The sample included 344 adopted children in first grade and their biological and adoptive parents. Results indicated that adoptees' reading scores were correlated with their biological parents' scores, but not with their adoptive parents' scores, suggesting genetic influences. In addition, examination of mean scores indicated that adoptees' scores were significantly greater than their biological parents' (p's < .001) for all subtests, suggesting promotive effects of the rearing environment. This pattern was present even when biological parents scored >1 standard deviation below the biological parent mean on achievement.

Preventive digital mental health interventions for children and young people: a review of the design and reporting of research.

Digital health interventions (DHIs) have frequently been highlighted as one way to respond to increasing levels of mental health problems in children and young people. Whilst many are developed to address existing mental health problems, there is also potential for DHIs to address prevention and early intervention. However, there are currently limitations in the design and reporting of the development, evaluation and implementation of preventive DHIs that can limit their adoption into real-world practice. This scoping review aimed to examine existing evidence-based DHI interventions and review how well the research literature described factors that researchers need to include in their study designs and reports to support real-world implementation. A search was conducted for relevant publications published from 2013 onwards. Twenty-one different interventions were identified from 30 publications, which took a universal (n = 12), selective (n = 3) and indicative (n = 15) approach to preventing poor mental health. Most interventions targeted adolescents, with only two studies including children aged ≤10 years. There was limited reporting of user co-design involvement in intervention development. Barriers and facilitators to implementation varied across the delivery settings, and only a minority reported financial costs involved in delivering the intervention. This review found that while there are continued attempts to design and evaluate DHIs for children and young people, there are several points of concern. More research is needed with younger children and those from poorer and underserved backgrounds. Co-design processes with children and young people should be recognised and reported as a necessary component within DHI research as they are an important factor in the design and development of interventions, and underpin successful adoption and implementation. Reporting the type and level of human support provided as part of the intervention is also important in enabling the sustained use and implementation of DHIs.

Examining the Role of Genetic Risk and Longitudinal Transmission Processes Underlying Maternal Parenting and Psychopathology and Children's ADHD Symptoms and Aggression: Utilizing the Advantages of a Prospective Adoption Design.

Although genetic factors may contribute to initial liability for ADHD onset, there is growing evidence of the potential importance of the rearing environment on the developmental course of ADHD symptomatology. However, associations between family-level variables (maternal hostility, maternal depressive symptoms) and child behaviors (developmental course of ADHD and aggression) may be explained by genes that are shared by biologically related parents and children. Furthermore, ADHD symptoms and aggression commonly co-occur: it is important to consider both simultaneously to have a better understanding of processes underlying the developmental course of ADHD and aggression. To addresses these issues, we employed a longitudinal genetically sensitive parent-offspring adoption design. Analyses were conducted using Cohort I (n = 340) of the Early Growth and Development Study with cross-validation analyses conducted with Cohort II (n = 178). Adoptive mother hostility, but not depression, was associated with later child ADHD symptoms and aggression. Mothers and their adopted children were genetically unrelated, removing passive rGE as a possible explanation. Early child impulsivity/activation was associated with later ADHD symptoms and aggression. Child impulsivity/activation was also associated with maternal hostility, with some evidence for evocative gene-environment correlation processes on adoptive mother depressive symptoms. This study provides novel insights into family-based environmental influences on child ADHD and aggression symptoms, independent of shared parental genetic factors, implications of which are further explicated in the discussion.

Maternal and paternal influences on childhood anxiety symptoms: A genetically sensitive comparison.

This study tested the theory that anxious fathers pose a quantitatively different environmental influence on childhood anxiety than anxious mothers. The analysed sample contained 502 linked adoption units from the Early Growth and Development Study (EGDS), a longitudinal multisite study that follows 561 adopted children (57.2% boys) and their adoptive and birth parents, who were recruited through US adoption agencies. A Bayesian latent growth model predicted child anxiety symptoms between 18 months and 4.5 years from inherited (birth parent anxiety) and rearing parent anxiety. This model revealed little evidence for a difference in the influence of maternal and paternal rearing parent anxiety on child anxiety symptoms. Contrary to theoretical predictions, anxiety in the rearing father is likely to have an equivalent influence to that of the mother on both child anxiety symptoms at 18 months old and their developmental trajectory over the preschool years.

Longitudinal examination of pathways to peer problems in middle childhood: A siblings-reared-apart design.

To advance research from Dishion and others on associations between parenting and peer problems across childhood, we used a sample of 177 sibling pairs reared apart since birth (because of adoption of one of the siblings) to examine associations between parental hostility and children's peer problems when children were ages 7 and 9.5 years (n = 329 children). We extended conventional cross-lagged parent-peer models by incorporating child inhibitory control as an additional predictor and examining genetic contributions via birth mother psychopathology. Path models indicated a cross-lagged association from parental hostility to later peer problems. When child inhibitory control was included, birth mother internalizing symptoms were associated with poorer child inhibitory control, which was associated with more parental hostility and peer problems. The cross-lagged paths from parental hostility to peer problems were no longer significant in the full model. Multigroup analyses revealed that the path from birth mother internalizing symptoms to child inhibitory control was significantly higher for birth parent-reared children, indicating the possible contribution of passive gene-environment correlation to this association. Exploratory analyses suggested that each child's unique rearing context contributed to his or her inhibitory control and peer behavior. Implications for the development of evidence-based interventions are discussed.

Siblings reared apart: A sibling comparison study on rearing environment differences.

A plethora of studies with parents and children who are biologically related has shown that the family environment plays an important role in child development. However, scientists have long known that a rigorous examination of environmental effects requires research designs that go beyond studies of genetically linked family members. Harnessing the principles of sibling comparison and animal cross-fostering designs, we introduce a novel approach: the siblings-reared-apart design. Supplementing the traditional adoption design of adopted child and adoptive parents with a sample of the adopted children's birth parents who raised their biological child(ren) at home (i.e., biological siblings of adoptees), this design provides opportunities to evaluate the role of specific rearing environments. In this proof of concept approach, we tested whether rearing environments differed between adoptive and birth families. Using data from 118 sets of adoption-linked families, each consisting of an adoptive family and the adoptee's birth family, both of whom are raising at least a child in each home, we found that compared with families in the birth homes, (a) adoptive families had higher household incomes and maternal educational attainment; (b) adoptive mothers displayed more guiding parenting, less harsh parenting, and less maternal depression; and (c) socioeconomic differences between the two homes did not account for the behavioral differences in mothers. We discuss the potential of the sibling-reared-apart design to advance developmental science. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Associations between schizophrenia genetic risk, anxiety disorders and manic/hypomanic episode in a longitudinal population cohort study.

BACKGROUND: Studies involving clinically recruited samples show that genetic liability to schizophrenia overlaps with that for several psychiatric disorders including bipolar disorder, major depression and, in a population study, anxiety disorder and negative symptoms in adolescence.AimsWe examined whether, at a population level, association between schizophrenia liability and anxiety disorders continues into adulthood, for specific anxiety disorders and as a group. We explored in an epidemiologically based cohort the nature of adult psychopathology sharing liability to schizophrenia. METHOD: Schizophrenia polygenic risk scores (PRSs) were calculated for 590 European-descent individuals from the Christchurch Health and Development Study. Logistic regression was used to examine associations between schizophrenia PRS and four anxiety disorders (social phobia, specific phobia, panic disorder and generalised anxiety disorder), schizophrenia/schizophreniform disorder, manic/hypomanic episode, alcohol dependence, major depression, and - using linear regression - total number of anxiety disorders. A novel population-level association with hypomania was tested in a UK birth cohort (Avon Longitudinal Study of Parents and Children). RESULTS: Schizophrenia PRS was associated with total number of anxiety disorders and with generalised anxiety disorder and panic disorder. We show a novel population-level association between schizophrenia PRS and manic/hypomanic episode. CONCLUSIONS: The relationship between schizophrenia liability and anxiety disorders is not restricted to psychopathology in adolescence but is present in adulthood and specifically linked to generalised anxiety disorder and panic disorder. We suggest that the association between schizophrenia liability and hypomanic/manic episodes found in clinical samples may not be due to bias.Declarations of interestNone.

Resilience in high-risk adolescents of mothers with recurrent depressive disorder: The contribution of fathers.

This study examines the role of paternal emotional support as a resilience promoter in offspring of mothers with depression by considering the role of fathers' mental health and the quality of the couple relationship. Two hundred and sixty-five mothers with recurrent unipolar depression, partners and adolescents from Wales were assessed. Paternal emotional support, couple relationship quality, and paternal depression were assessed at baseline; adolescent mental health symptoms were assessed using the Child and Adolescent Psychiatric Assessment at follow-up. Results showed evidence of an indirect pathway whereby couple relationship quality predicted paternal emotional support (ß = -.21, 95% CI [-.34, -.08]; p = .002) which in turn predicted adolescent depression (ß = -.18, 95% CI [-.33, -.04]; p = .02), but not disruptive behaviours (ß = -.08, 95% CI [-.22, .07]; p = .30), after controlling for relevant confounders. The findings highlight that fathers and the broader family system play an important role in enhancing resilience to depression symptoms in at-risk adolescents.

Annual Research Review: Interparental conflict and youth psychopathology: an evidence review and practice focused update.

The quality of the interparental relationship is recognized as an important influence on child and adolescent psychopathology. Historically, clinically oriented research on this topic has focused on the impacts of parental divorce and domestic violence as primary interparental relationship influences on child outcomes, to the relative neglect of dimensional or qualitative features of the couple/interparental relationship for youth (child and adolescent) psychopathology. Recent research has highlighted that children are affected by attributes of interparental conflict, specifically how parents express and manage conflicts in their relationship, across a continuum of expressed severity and negativity - ranging from silence to violence. Furthermore, new evidence highlights that children's emotional, behavioral, social, academic outcomes, and future interpersonal relationships are adversely affected by conflict between parents/carers whether adults are living together or not (i.e. married or separated), or where children are or are not genetically related to their rearing parents (e.g. adoption). We review evidence and present an integrated theoretical model, highlighting how children are affected by interparental conflict and what this evidence base means for effective intervention and prevention program development, as well as the development of possible cost-benefit models. Additionally, we review policy implications of this research and highlight some very recent examples of UK-based policy focusing on addressing the interparental relationship and its impact on youth psychopathology.

Naturalistic Experimental Designs as Tools for Understanding the Role of Genes and the Environment in Prevention Research.

Before genetic approaches were applied in experimental studies with human populations, they were used by animal and plant breeders to observe, and experimentally manipulate, the role of genes and environment on specific phenotypic or behavioral outcomes. For obvious ethical reasons, the same level of experimental control is not possible in human populations. Nonetheless, there are natural experimental designs in human populations that can serve as logical extensions of the rigorous quantitative genetic experimental designs used by animal and plant researchers. Applying concepts such as cross-fostering and common garden rearing approaches from the life science discipline, we describe human designs that can serve as naturalistic proxies for the controlled quantitative genetic experiments facilitated in life sciences research. We present the prevention relevance of three such human designs: (1) children adopted at birth by parents to whom they are not genetically related (common garden approach); (2) sibling designs where one sibling is reared from birth with unrelated adoptive parents and the other sibling is reared from birth by the biological mother of the sibling pair (cross-fostering approach); and (3) in vitro fertilization designs, including egg donation, sperm donation, embryo donation, and surrogacy (prenatal cross-fostering approach). Each of these designs allows for differentiation of the effects of the prenatal and/or postnatal rearing environment from effects of genes shared between parent and child in naturalistic ways that can inform prevention efforts. Example findings from each design type are provided and conclusions drawn about the relevance of naturalistic genetic designs to prevention science.

Using an adoption-biological family design to examine associations between maternal trauma, maternal depressive symptoms, and child internalizing and externalizing behaviors.

Maternal trauma is a complex risk factor that has been linked to adverse child outcomes, yet the mechanisms underlying this association are not well understood. This study, which included adoptive and biological families, examined the heritable and environmental mechanisms by which maternal trauma and associated depressive symptoms are linked to child internalizing and externalizing behaviors. Path analyses were used to analyze data from 541 adoptive mother-adopted child (AM-AC) dyads and 126 biological mother-biological child (BM-BC) dyads; the two family types were linked through the same biological mother. Rearing mother's trauma was associated with child internalizing and externalizing behaviors in AM-AC and BM-BC dyads, and this association was mediated by rearing mothers' depressive symptoms, with the exception of biological child externalizing behavior, for which biological mother trauma had a direct influence only. Significant associations between maternal trauma and child behavior in dyads that share only environment (i.e., AM-AC dyads) suggest an environmental mechanism of influence for maternal trauma. Significant associations were also observed between maternal depressive symptoms and child internalizing and externalizing behavior in dyads that were only genetically related, with no shared environment (i.e., BM-AC dyads), suggesting a heritable pathway of influence via maternal depressive symptoms.

How Can Genetically Informed Research Help Inform the Next Generation of Interparental and Parenting Interventions?

There is robust evidence that the interparental relationship and parenting behaviors each have a significant influence on children's risk for emotional (internalizing) and behavioral (externalizing) problems. Indeed, interventions targeting the interparental relationship and parenting processes show significant intervention-related reductions in child internalizing and externalizing problems. However, most evidence-based parenting- and couple-focused interventions result in small to medium effects on children's emotional and behavior problems. It is proposed that there is opportunity to improve upon these interventions through incorporation of knowledge from quantitative genetic research. Three core recommendations are provided for practitioners engaging in intervention work with children and families. These recommendations are contextualized relative to what quantitative genetic studies can tell us about the role of the interparental relationship and parenting behaviors on child outcomes.