A Systematic Review and Meta-analysis: Paternal Anxiety and the Emotional and Behavioral Outcomes in Their Offspring.

OBJECTIVE: Anxiety disorders are highly prevalent worldwide; however, the literature lacks a meta-analytic quantification of the risk posed by fathers' anxiety for offspring development. This systematic review and meta-analysis aimed to provide a comprehensive estimate of the magnitude of the association between paternal anxiety and emotional and behavioral problems of offspring. METHOD: In February 2022, Web of Science, Ovid (Embase, MEDLINE, PsycINFO), Trip Database, and ProQuest were searched to identify all quantitative studies that measured anxiety in fathers and emotional and/or behavioral outcomes in offspring. No limits were set for offspring age, publication language, or publication year. Summary estimates were extracted from the primary studies. Meta-analytic random-effects 3-level models were used to calculate correlation coefficients. Quality was assessed using the Newcastle-Ottawa Scale. The study protocol was preregistered with PROSPERO (CRD42022311501) and adhered to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) reporting guidelines. RESULTS: Of 11,746 records identified, 98 were included in the meta-analysis. Small but significant associations were found between paternal anxiety and offspring emotional and behavioral problems overall (r = 0.16, 95% CI [0.13, 0.19]) and behavioral (r = 0.19, 95% CI [0.13, 0.24]), emotional (r = 0.15, 95% CI [0.12, 0.18]), anxiety (r = 0.13, 95% CI [0.11, 0.16]), and depression (r = 0.13, 95% CI [0.03, 0.23]) problems. Some significant moderators were identified. CONCLUSION: Paternal mental health is associated with offspring development, and the offspring of fathers with anxiety symptoms or disorders are at increased risk of negative emotional and behavioral outcomes, in line with the principles of multifinality and pleiotropy. The substantial heterogeneity among studies and the overrepresentation of White European American groups in this literature highlight the need for further research. DIVERSITY & INCLUSION STATEMENT: While citing references scientifically relevant for this work, we also actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our reference list.

Intergenerational consequences of racism in the United Kingdom: a qualitative investigation into parents' exposure to racism and offspring mental health and well-being.

BACKGROUND: Experiences of racism are linked to negative physical and mental health outcomes among those exposed. According to quantitative research derived mainly from the United States, these negative outcomes can have cascading effects in families, when parents' experiences of racism indirectly impact offspring. New research is warranted for families in the United Kingdom, informed by a qualitative approach to canvassing community knowledge and perspectives, exploring how existing findings relate to lived experiences. METHOD: We conducted four online focus groups with 14 parents of school-aged children and 14 adolescents who had experienced racism in the United Kingdom. Participants were asked what children know of parents' experiences of racism, and how these experiences can impact parent-child interactions, mental health and well-being. Focus group recordings were transcribed, data coded and analysed through iterative categorisation. RESULTS: Analyses drew four themes from participants' insights. Together, themes illuminated the pervasive nature of racism experienced by some families in the United Kingdom. Parent and child experiences of racism were connected and co-occurring, with indirect effects impacting mental health and well-being in both generations. These experiences were linked to both positive and negative changes in parenting behaviour and parent-child relationships, which could be moderated by intersecting identities such as the parent's generational status for immigration to the United Kingdom. Social cohesion, safe spaces and education programmes were highlighted for future intervention. CONCLUSIONS: Findings corroborate existing literature, while further emphasising a broader bidirectional picture, requiring a family system and intersectional approach to understanding the mental health impact of racism in families. Avenues for future research are discussed to support development of equitable intervention and support strategies to prevent racism and support those affected.

Assessing aetiological overlap between child and adult attention-deficit hyperactivity disorder symptoms in an extended family design.

BACKGROUND: Several longitudinal studies have cast doubt on the aetiological overlap between child and adult attention-deficit hyperactivity disorder (ADHD). However, a lack of genetically sensitive data following children across adulthood precludes direct evaluation of aetiological overlap between child and adult ADHD. AIMS: We circumvent the existing gap in longitudinal data by exploring genetic overlap between maternal (adult) and offspring (child) ADHD and comorbid symptoms in an extended family cohort. METHOD: Data were drawn from the Norwegian Mother, Father and Child Cohort Study, a Norwegian birth registry cohort of 114 500 children and their parents. Medical Birth Registry of Norway data were used to link extended families. Mothers self-reported their own ADHD symptoms when children were aged 3 years; reported children's ADHD symptoms at age 5 years; and children's ADHD, oppositional defiant disorder (ODD), conduct disorder, anxiety and depression symptoms at age 8 years. Genetic correlations were derived from Multiple-Children-of-Twins-and-Siblings and extended bivariate twin models. RESULTS: Phenotypic correlations between adult ADHD symptoms and child ADHD, ODD, conduct disorder, anxiety and depression symptoms at age 8 years were underpinned by medium-to-large genetic correlations (child ADHD: rG = 0.55, 95% CI 0.43-0.93; ODD: rG = 0.80, 95% CI 0.46-1; conduct disorder: rG = 0.44, 95% CI 0.28-1; anxiety: rG = 0.72, 95% CI 0.48-1; depression: rG = 1, 95% CI 0.66-1). These cross-generational adult-child genetic correlations were of a comparable magnitude to equivalent child-child genetic correlations with ADHD symptoms at age 5 years. CONCLUSIONS: Our findings provide genetically sensitive evidence that ADHD symptoms in adulthood share a common genetic architecture with symptoms of ADHD and four comorbid disorders at age 8 years. These findings suggest that in the majority of cases, ADHD symptoms in adulthood are not aetiologically distinct from in childhood.

A meta-analysis of genetic effects associated with neurodevelopmental disorders and co-occurring conditions.

A systematic understanding of the aetiology of neurodevelopmental disorders (NDDs) and their co-occurrence with other conditions during childhood and adolescence remains incomplete. In the current meta-analysis, we synthesized the literature on (1) the contribution of genetic and environmental factors to NDDs, (2) the genetic and environmental overlap between different NDDs, and (3) the co-occurrence between NDDs and disruptive, impulse control and conduct disorders (DICCs). Searches were conducted across three platforms: Web of Science, Ovid Medline and Ovid Embase. Studies were included only if 75% or more of the sample consisted of children and/or adolescents and the studies had measured the aetiology of NDDs and DICCs using single-generation family designs or genomic methods. Studies that had selected participants on the basis of unrelated diagnoses or injuries were excluded. We performed multilevel, random-effects meta-analyses on 296 independent studies, including over four million (partly overlapping) individuals. We further explored developmental trajectories and the moderating roles of gender, measurement, geography and ancestry. We found all NDDs to be substantially heritable (family-based heritability, 0.66 (s.e. = 0.03); SNP heritability, 0.19 (s.e. = 0.03)). Meta-analytic genetic correlations between NDDs were moderate (grand family-based genetic correlation, 0.36 (s.e. = 0.12); grand SNP-based genetic correlation, 0.39 (s.e. = 0.19)) but differed substantially between pairs of disorders. The genetic overlap between NDDs and DICCs was strong (grand family-based genetic correlation, 0.62 (s.e. = 0.20)). While our work provides evidence to inform and potentially guide clinical and educational diagnostic procedures and practice, it also highlights the imbalance in the research effort that has characterized developmental genetics research.

Annual Research Review: Towards a deeper understanding of nature and nurture: combining family-based quasi-experimental methods with genomic data.

Distinguishing between the effects of nature and nurture constitutes a major research goal for those interested in understanding human development. It is known, for example, that many parent traits predict mental health outcomes in children, but the causal processes underlying such associations are often unclear. Family-based quasi-experimental designs such as sibling comparison, adoption and extended family studies have been used for decades to distinguish the genetic transmission of risk from the environmental effects family members potentially have on one another. Recently, these designs have been combined with genomic data, and this combination is fuelling a range of exciting methodological advances. In this review we explore these advances - highlighting the ways in which they have been applied to date and considering what they are likely to teach us in the coming years about the aetiology and intergenerational transmission of psychopathology.

Using twin-pairs to assess potential bias in polygenic prediction of externalising behaviours across development.

Prediction from polygenic scores may be confounded sources of passive gene-environment correlation (rGE; e.g. population stratification, assortative mating, and environmentally mediated effects of parental genotype on child phenotype). Using genomic data from 10,000 twin pairs, we asked whether polygenic scores from the recent externalising genome-wide association study predicted conduct problems, ADHD symptomology and callous-unemotional traits, and whether these predictions are biased by rGE. We ran regression models including within-family and between-family polygenic scores, to separate the direct genetic influence on a trait from environmental influences that correlate with genes (indirect genetic effects). Findings suggested that this externalising polygenic score is a good index of direct genetic influence on conduct and ADHD-related symptoms across development, with minimal bias from rGE, although the polygenic score predicted less variance in CU traits. Post-hoc analyses showed some indirect genetic effects acting on a common factor indexing stability of conduct problems across time and contexts.

Parental criticism and adolescent internalising symptoms: using a Children-of-Twins design with power calculations to account for genetic influence.

BACKGROUND: Parental criticism is correlated with internalising symptoms in adolescent offspring. This correlation could in part reflect their genetic relatedness, if the same genes influence behaviours in both parents and offspring. We use a Children-of-Twins design to assess whether parent-reported criticism and offspring internalising symptoms remain associated after controlling for shared genes. To aid interpretation of our results and those of previous Children-of-Twins studies, we examine statistical power for the detection of genetic effects and explore the direction of possible causal effects between generations. METHODS: Data were drawn from two Swedish twin samples, comprising 876 adult twin pairs with adolescent offspring and 1,030 adolescent twin pairs with parents. Parent reports of criticism towards their offspring were collected concurrently with parent and offspring reports of adolescent internalising symptoms. Children-of-Twins structural equation models were used to control for genetic influence on the intergenerational association between parental criticism and adolescent internalising. RESULTS: Parental criticism was associated with adolescent internalising symptoms after controlling for genetic influence. No significant role was found for shared genes influencing phenotypes in both generations, although power analyses suggested that some genetic effects may have gone undetected. Models could not distinguish directionality for nongenetic, causal effects between generations. CONCLUSIONS: Parental criticism may be involved in psychosocial family processes in the context of adolescent internalising. Future studies should seek to identify these processes and provide clarity on the direction of potential causal effects.

Systematic Review and Meta-analysis of Genetically Informed Research: Associations Between Parent Anxiety and Offspring Internalizing Problems.

OBJECTIVE: Parent anxiety is associated with offspring internalizing problems (emotional problems related to anxiety and depression). This may reflect causal processes, whereby exposure to parent anxiety directly influences offspring internalizing (and/or vice versa). However, parent-offspring associations could also be attributable to their genetic relatedness. A systematic review and meta-analysis were conducted to investigate whether exposure to parent anxiety is associated with offspring internalizing after controlling for genetic relatedness. METHOD: A literature search across 5 databases identified 429 unique records. Publications were retained if they used a quasi-experimental design in a general population sample to control for participant relatedness in associations between parent anxiety and offspring internalizing outcomes. Publications were excluded if they involved an experimental exposure or intervention. Studies of prenatal and postnatal anxiety exposure were meta-analyzed separately. Pearson's correlation coefficient estimates (r) were pooled using multilevel random-effects models. RESULTS: Eight publications were retained. Data were drawn from 4 population cohorts, each unique to a quasi-experimental design: adoption, sibling-comparison, children-of-twins or in vitro fertilization. Cohorts were located in northern Europe or America. Families were predominantly of European ancestry. Three publications (Nfamilies >11,700; offspring age range, 0.5-10 years) showed no association between prenatal anxiety exposure and offspring internalizing outcomes after accounting for participant relatedness (r = .04; 95% CI: -.07, .14). Six publications (Nfamilies >12,700; offspring age range, 0.75-22 years) showed a small but significant association between concurrent symptoms in parents and offspring after accounting for participant relatedness (r = .13; 95% CI: .04, .21). CONCLUSION: Initial literature, derived from homogeneous populations, suggests that prenatal anxiety exposure does not cause offspring internalizing outcomes. However, postnatal anxiety exposure may be causally associated with concurrent offspring internalizing via nongenetic pathways. Longitudinal stability, child-to-parent effects, and the role of moderators and methodological biases require attention.

How important are parents in the development of child anxiety and depression? A genomic analysis of parent-offspring trios in the Norwegian Mother Father and Child Cohort Study (MoBa).

BACKGROUND: Many studies detect associations between parent behaviour and child symptoms of anxiety and depression. Despite knowledge that anxiety and depression are influenced by a complex interplay of genetic and environmental risk factors, most studies do not account for shared familial genetic risk. Quantitative genetic designs provide a means of controlling for shared genetics, but rely on observed putative exposure variables, and require data from highly specific family structures. METHODS: The intergenerational genomic method, Relatedness Disequilibrium Regression (RDR), indexes environmental effects of parents on child traits using measured genotypes. RDR estimates how much the parent genome influences the child indirectly via the environment, over and above effects of genetic factors acting directly in the child. This 'genetic nurture' effect is agnostic to parent phenotype and captures unmeasured heritable parent behaviours. We applied RDR in a sample of 11,598 parent-offspring trios from the Norwegian Mother, Father and Child Cohort Study (MoBa) to estimate parental genetic nurture separately from direct child genetic effects on anxiety and depression symptoms at age 8. We tested for mediation of genetic nurture via maternal anxiety and depression symptoms. Results were compared to a complementary non-genomic pedigree model. RESULTS: Parental genetic nurture explained 14% of the variance in depression symptoms at age 8. Subsequent analyses suggested that maternal anxiety and depression partially mediated this effect. The genetic nurture effect was mirrored by the finding of family environmental influence in our pedigree model. In contrast, variance in anxiety symptoms was not significantly influenced by common genetic variation in children or parents, despite a moderate pedigree heritability. CONCLUSIONS: Genomic methods like RDR represent new opportunities for genetically sensitive family research on complex human traits, which until now has been largely confined to adoption, twin and other pedigree designs. Our results are relevant to debates about the role of parents in the development of anxiety and depression in children, and possibly where to intervene to reduce problems.

Children of the Twins Early Development Study (CoTEDS): A Children-of-Twins Study.

The Children of the Twins Early Development Study (CoTEDS) is a new prospective children-of-twins study in the UK, designed to investigate intergenerational associations across child developmental stages. CoTEDS will enable research on genetic and environmental factors that underpin parent-child associations, with a focus on mental health and cognitive-related traits. Through CoTEDS, we will have a new lens to examine the roles that parents play in influencing child development, as well as the genetic and environmental factors that shape parenting behavior and experiences. Recruitment is ongoing from the sample of approximately 20,000 contactable adult twins who have been enrolled in the Twins Early Development Study (TEDS) since infancy. TEDS twins are invited to register all offspring to CoTEDS at birth, with 554 children registered as of May 2019. By recruiting the second generation of TEDS participants, CoTEDS will include information on adult twins and their offspring from infancy. Parent questionnaire-based data collection is now underway for 1- and 2-year-old CoTEDS infants, with further waves of data collection planned. Current data collection includes the following primary constructs: child mental health, temperament, language and cognitive development; parent mental health and social relationships; parenting behaviors and feelings; and other socioecological factors. Measurement tools have been selected with reference to existing genetically informative cohort studies to ensure overlap in phenotypes measured at corresponding stages of development. This built-in study overlap is intended to enable replication and triangulation of future analyses across samples and research designs. Here, we summarize study protocols and measurement procedures and describe future plans.

Anxiety in the family: a genetically informed analysis of transactional associations between mother, father and child anxiety symptoms.

BACKGROUND: Anxiety in parents is associated with anxiety in offspring, although little is known about the mechanisms underpinning these intergenerational associations. We conducted the first genetically sensitive study to simultaneously examine the effects of mother, father and child anxiety symptoms on each other over time. METHOD: Adoptive parent and child symptoms were measured at child ages 6, 7 and 8 years from 305 families involved in the Early Growth and Development Study, using a prospective adoption design. Children were adopted at birth to nonrelatives, and composite data on internalising problems within birth families were used as a proxy measure of offspring inherited risk for anxiety. Structural equation models were fitted to the data to examine prospective associations between adoptive mother, father and child symptoms, whilst accounting for individuals' symptom stability over time. RESULTS: Child anxiety symptoms at age 7 predicted adoptive mothers' anxiety symptoms at age 8. No mother-to-child or child-to-father effects were observed. These results were consistent in sensitivity analyses using only paternal offspring reports and using a second measure of child anxiety symptoms. Fathers' anxiety symptoms at child age 6 prospectively predicted child symptoms, but only when paternal offspring reports were included in the model. Composite data on birth family internalising problems were not associated with child anxiety symptoms. CONCLUSIONS: Results show environmentally mediated associations between parent and child anxiety symptoms. Results support developmental theories suggesting that child anxiety symptoms can exert influence on caregivers, and mothers and fathers may play unique roles during the development of child symptoms. Further research is needed on the role of genetic transmission associated with anxiety symptoms in biologically related families. In the meantime, researchers and clinicians should strive to include fathers in assessments and consider the effects of child symptoms on caregivers.