Language, Motor Ability and Related Deficits in Children at Familial Risk of Schizophrenia or Bipolar Disorder.

Background: It is known that impairments in linguistic ability and motor function tend to co-occur in children, and that children from families with parental mental illness such as schizophrenia tend to perform poorly in both domains, but the exact nature of these links has not yet been fully elucidated.

Design: In this study, we leveraged the first wave of the Danish High Risk and Resilience Study (VIA 7), which includes both genetic data and measures covering multiple developmental domains. The VIA 7 cohort comprises 522 7-year-old children born to parents with schizophrenia (N = 202), bipolar disorder (N = 120) or neither (N = 200).

Brain Activation and Aberrant Effective Connectivity in the Mentalizing Network of Preadolescent Children at Familial High Risk of Schizophrenia or Bipolar Disorder.

Background: Schizophrenia and bipolar disorder are characterized by social cognitive impairments, and recent research has identified alterations of the social brain. However, it is unknown whether familial high risk (FHR) of these disorders is associated with neurobiological alterations already present in childhood.

Methods: As part of the Danish High Risk and Resilience Study-VIA 11, we examined children at FHR of schizophrenia (n = 121, 50% female) or bipolar disorder (n = 75, 47% female) and population-based control children (PBCs) (n = 128, 48% female).

Comparing cognition in parents with schizophrenia or bipolar disorder and their 7-year-old offspring.

Individuals with schizophrenia (SZ) or bipolar disorder (BP) display cognitive impairments, while their first-degree relatives perform at an intermediate level between the patient groups and controls. However, the environmental impact of having an ill relative likely varies with the type of kinship and some studies suggest that offspring may be particularly disadvantaged. The present study aimed to investigate the relationship between parent and child cognition in parents with SZ or BD and their 7-year-old offspring.

Executive Control and Associated Brain Activity in Children With Familial High-Risk of Schizophrenia or Bipolar Disorder: A Danish Register-based Study.

Background And Hypotheses: Impaired executive control is a potential prognostic and endophenotypic marker of schizophrenia (SZ) and bipolar disorder (BP). Assessing children with familial high-risk (FHR) of SZ or BP enables characterization of early risk markers and we hypothesize that they express impaired executive control as well as aberrant brain activation compared to population-based control (PBC) children.

Study Design: Using a flanker task, we examined executive control together with functional magnetic resonance imaging (fMRI) in 11- to 12-year-old children with FHR of SZ (FHR-SZ) or FHR of BP (FHR-BP) and PBC children as part of a register-based, prospective cohort-study; The Danish High Risk and Resilience study-VIA 11.

Pubertal timing, sex hormone levels, and associations between early life adversity and accelerated development amongst 11-year-old children of parents with schizophrenia or bipolar disorder and controls: The Danish high risk and Resilience study via 11.

Background: Children of parents with severe mental illness have several known risk factors for altered pubertal timing. Pubertal timing is important for children's physical and emotional development. We aimed to examine pubertal timing and associations between pubertal timing, early life adversity and child problem behavior including psychiatric diagnoses among children of parents with schizophrenia or bipolar disorder and controls.

Social responsiveness in families with parental schizophrenia or bipolar disorder-The Danish High Risk and Resilience Study.

Schizophrenia and bipolar disorder are highly heritable severe mental disorders associated with social impairments. Moreover, partners to individuals with one of these disorders display poorer functioning and more psychopathology, but their social skills and the transgenerational transmission remains uninvestigated. Therefore, we aimed to examine social responsiveness in families with parental schizophrenia or bipolar disorder.

Affective lability in parents with schizophrenia or bipolar disorder and their co-parents - The Danish High Risk and Resilience Study VIA 7.

In bipolar disorder, dysregulation of affect is a core feature while knowledge on affective lability in schizophrenia is sparse. Research on affective lability in partners to individuals with schizophrenia or bipolar disorder is also lacking. The objective of this study was to investigate affective lability in parents with schizophrenia or bipolar disorder, and their co-parents without these disorders.

Early Childhood Neurocognition in Relation to Middle Childhood Psychotic Experiences in Children at Familial High Risk of Schizophrenia or Bipolar Disorder and Population-Based Controls: The Danish High Risk and Resilience Study.

Background And Hypothesis: Familial high-risk (FHR) studies examining longitudinal associations between neurocognition and psychotic experiences are currently lacking. We hypothesized neurocognitive impairments at age 7 to be associated with increased risk of psychotic experiences from age 7 to 11 in children at familial high risk of schizophrenia (FHR-SZ) or bipolar disorder (FHR-BP) and population-based controls (PBC), and further, impaired functioning in some neurocognitive functions to be associated with greater risk of psychotic experiences in children at FHR-SZ or FHR-BP relative to PBC.

Study Design: Neurocognition was assessed at age 7 (early childhood) and psychotic experiences from age 7 to 11 (middle childhood) in 449 children from the Danish High Risk and Resilience Study.

A family-based study of genetic and epigenetic effects across multiple neurocognitive, motor, social-cognitive and social-behavioral functions.

Many psychiatric and neurodevelopmental disorders are known to be heritable, but studies trying to elucidate the genetic architecture of such traits often lag behind studies of somatic traits and diseases. The reasons as to why relatively few genome-wide significant associations have been reported for such traits have to do with the sample sizes needed for the detection of small effects, the difficulty in defining and characterizing the phenotypes, partially due to overlaps in affected underlying domains (which is especially true for cognitive phenotypes), and the complex genetic architectures of the phenotypes, which are not wholly captured in traditional case-control GWAS designs. We aimed to tackle the last two issues by performing GWASs of eight quantitative neurocognitive, motor, social-cognitive and social-behavioral traits, which may be considered endophenotypes for a variety of psychiatric and neurodevelopmental conditions, and for which we employed models capturing both general genetic association and parent-of-origin effects, in a family-based sample comprising 402 children and their parents (mostly family trios).

Association Between Early Risk Factors and Level of Functioning at Age Seven in Children at Familial Risk for Schizophrenia Or Bipolar Disorder - the Danish High Risk and Resilience Study VIA 7.

Background: Facing multiple risk factors, relative to single risk factor exposure early in life can have great implications for negative child development.

Objective: We aim to examine whether the prevalence of early risk factors is higher among children with familial high risk for schizophrenia or bipolar disorder compared to controls. Further, to investigate the association between number of early risk factors and level of functioning at age seven, and whether this possible association is different in children with familial high risk compared to controls.

Neurocognitive Subgroups in Children at Familial High-risk of Schizophrenia or Bipolar disorder: Subgroup Membership Stability or Change From Age 7 to 11-The Danish High Risk and Resilience Study.

Background And Hypothesis: Subgroups with distinct levels of neurocognitive functioning exist in children of parents with schizophrenia or bipolar disorder. However, studies investigating the temporal stability of subgroup membership are currently lacking. We hypothesized that a minority of children at familial high-risk of schizophrenia (FHR-SZ) or bipolar disorder (FHR-BP) would transition to a different neurocognitive subgroup from age 7 to 11 and that most transitions would be to a more impaired subgroup.

Developmental Pathways and Clinical Outcomes of Early Childhood Psychotic Experiences in Preadolescent Children at Familial High Risk of Schizophrenia or Bipolar Disorder: A Prospective, Longitudinal Cohort Study - The Danish High Risk and Resilience Study, VIA 11.

Objective: Psychotic experiences are common in children and adolescents and are associated with concurrent and subsequent psychopathology. Most findings originate from general population studies, whereas little is known of the clinical outcomes of psychotic experiences in children and adolescents at familial high risk of psychosis. We examined the prevalence of psychotic experiences in middle childhood and whether early childhood psychotic experiences and developmental pathways of psychotic experiences predicted mental disorders in middle childhood in children at familial high risk of schizophrenia (FHR-SZ), bipolar disorder (FHR-BP), and a population-based control group.

Emotion regulation in 7-year-old children with familial high risk for schizophrenia or bipolar disorder compared to controls - The Danish High Risk and Resilience Study - VIA 7, a population-based cohort study.

Objectives: Emotion regulation is a predictor of overall life outcome. Problems of emotion regulation are associated with multiple psychiatric disorders and could be a potential treatment target for improving well-being and functioning. Children at familial high risk of severe mental illness have a markedly increased risk of various psychopathology and constitute a group at significant risk of emotion regulation problems.

Genetic assortative mating for schizophrenia and bipolar disorder.

Background: Psychiatric disorders are highly polygenic and show patterns of partner resemblance. Partner resemblance has direct population-level genetic implications if it is caused by assortative mating, but not if it is caused by convergence or social homogamy. Using genetics may help distinguish these different mechanisms.

Transmission of intelligence, working memory, and processing speed from parents to their seven-year-old offspring is function specific in families with schizophrenia or bipolar disorder.

Background: Prior studies have shown high heritability estimates regarding within-function transmission of neurocognition, both in healthy families and in families with schizophrenia but it remains an open question whether transmission from parents to offspring is function specific and whether the pattern is the same in healthy families and families with schizophrenia or bipolar disorder. We aimed to characterize the transmission of intelligence, processing speed, and verbal working memory functions from both biological parents to their 7-year-old offspring in families with parental schizophrenia, bipolar disorder, and population-based control parents.

Methods: The population-based cohort consists of 7-year-old children with one parent diagnosed with schizophrenia (n = 186), bipolar disorder (n = 114), and of parents without schizophrenia or bipolar disorder (n = 192).

Neurocognitive Development in Children at Familial High Risk of Schizophrenia or Bipolar Disorder.

Importance: Neurocognitive impairments exist in children at familial high risk (FHR) of schizophrenia and bipolar disorder. Studies on preadolescent developmental courses of neurocognition are important to describe shared and distinct neurodevelopmental pathways in these groups.

Objective: To assess the development in specific neurocognitive functions from age 7 to 11 years in children at FHR of schizophrenia or bipolar disorder compared with children in a population-based control (PBC) group.

Development of social responsiveness and theory of mind in children of parents with schizophrenia or bipolar disorder.

Social impairments are suggested as vulnerability markers for schizophrenia and bipolar disorder. Therefore, we investigated the development of social responsiveness and theory of mind (ToM) in children at familial high-risk of schizophrenia (FHR-SZ) or bipolar disorder (FHR-BP). This study is part of The Danish High Risk and Resilience Study, a longitudinal cohort study of children at FHR-SZ or FHR-BP and population-based controls (PBC).

Sex differences across developmental domains among children with a familial risk of severe mental disorders.

Background: Sex differences in brain structure and neurodevelopment occur in non-clinical populations. We investigated whether sex had a similar effect on developmental domains amongst boys and girls with a familial risk of schizophrenia (FHR-SZ), bipolar disorder (FHR-BP), and controls.

Methods: Through Danish registries, we identified 522 7-year-old children (242 girls) with FHR-SZ, FHR-BP, and controls.

Exploring protective and risk factors in the home environment in high-risk families - results from the Danish High Risk and Resilience Study-VIA 7.

Background: Exposure to inadequate home environment may put the healthy development of familial high-risk children at risk. This study aimed to investigate associations between risk factors and an adequate home environment of children having a parent diagnosed with schizophrenia or bipolar disorder.

Methods: From a cohort of 522 children, data from 463 7-year-old children was included.

Neurocognitive heterogeneity in 7-year-old children at familial high risk of schizophrenia or bipolar disorder: The Danish high risk and resilience study - VIA 7.

Background: Studies of neurocognitive heterogeneity in young children at familial high-risk of bipolar disorder (FHR-BP) or schizophrenia (FHR-SZ) are important to investigate inter-individual neurocognitive differences. We aimed to identify neurocognitive subgroups, describe prevalence of FHR-BP or FHR-SZ children herein, and examine risk ratios (RR) compared with controls.

Methods: In a population-based cohort of 514 7-year-old children (197 FHR-SZ, 118 FHR-BP, and 199 matched controls) we used hierarchical cluster analyses to identify subgroups across 14 neurocognitive indices.

A Nationwide Cohort Study of Nonrandom Mating in Schizophrenia and Bipolar Disorder.

Nonrandom mating in parents with schizophrenia or bipolar disorder increases the population-level genetic variance among the offspring generation and creates familial (risk) environments likely to be shaped by specific conditions. The objective of this study was to investigate the occurrence of mental disorder and levels of cognitive and social functioning in individuals who have children by partners with schizophrenia or bipolar disorder compared to controls. The Danish High Risk and Resilience Study VIA 7 is a population-based cohort study conducted in Denmark between 2013 and 2016.

Decision making and its associations to neurocognitive functions, psychopathology, and the home environment in seven-year-old children at familial high risk of schizophrenia or bipolar disorder: The Danish High Risk and Resilience Study VIA 7.

Background: Slower and suboptimal decision making has been identified in adults with schizophrenia and bipolar disorder. Owing to the limited evidence on decision making in first-degree relatives, we aimed to investigate, whether alterations in decision making are present in young children at familial high risk of bipolar disorder or schizophrenia.

Methods: In this population-based cohort study we assessed decision making in 197 children at familial high risk of schizophrenia (FHR-SZ), 115 children at familial high risk of bipolar disorder (FHR-BP), and 190 controls aged seven using the Cambridge Gambling Task.