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. Of these 172 children had familial risk for schizophrenia, 109 children had familial risk for bipolar disorder, and 190 were population-based controls. As part of a comprehensive battery, all participants were assessed with the Middle Childhood-Home Observation for Measurement of the Environment Inventory (MC-HOME Inventory) measuring the quality of the home environment. RESULTS: When analyzing all families together, we found that having a parent diagnosed with schizophrenia would have a negative impact on the home environment (ß = -1.08; 95% CI (-2.16;-0.01); p = 0.05), while familial risk for bipolar disorder did not show significant predictive value. Being a single caregiver and child having experienced severe life events from ages 4 to 7 showed significant negative impact, while child having a mental illness diagnosis did not. Being a female caregiver, good social functioning of the caregiver, high child IQ and not being a single caregiver were found to predict positive values for the home environment. We found similar results when analyzing caregivers with and without a diagnosis separately. CONCLUSIONS: Knowledge of what predicts good home environment should be used to inform development of early interventions for families at risk.

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. Investigations of emotion regulation in children at familial high risk of severe mental illness are sparse. METHODS: We applied an instrument for assessing emotion regulation, the Tangram Emotion Coding Manual (TEC-M), to a population-based cohort of 522 7-year-old children born to parents diagnosed with either schizophrenia or bipolar disorder and matched controls. The TEC-M is an ecologically valid, clinician-rated observational test measure of spontaneous emotion regulation. We aimed to compare emotion regulation between risk groups and to investigate associations between emotion regulation and psychopathology and daily life functioning, and between emotion regulation and an acknowledged questionnaire-based dysregulation profile. RESULTS: In this early developmental phase, we found no between group differences in emotion regulation. We found a significant but weak negative association between emotion regulation and both child psychopathology and the presence of a dysregulation profile on the Child Behavior Checklist and a weak positive association between emotion regulation and current level of functioning. CONCLUSIONS: These findings contribute to the understanding of emotion regulation in familial high-risk children and further studies of emotion regulation in children at familial high risk of severe mental illness are warranted.

Executive functions in 7-year-old children of parents with schizophrenia or bipolar disorder compared with controls: The Danish High Risk and Resilience Study-VIA 7, a population-based cohort study.

Cognitive impairments are strongly associated with schizophrenia (SZ) and bipolar disorder (BP) with executive functions (EF) impairments as a likely key feature. Studies of everyday behavior rated EF in young children at familial high risk of SZ (FHR-SZ) are scarce and, to our knowledge, non-existent in young children at familial high risk of BP (FHR-BP). We aimed to compare everyday behavior-rated EF of FHR-SZ, FHR-BP, and control children. A nationwide population-based cohort of 522 7-year-old children with parents diagnosed with either SZ (N = 202) or BP (N = 120) and matched controls (N = 200) were recruited using the Danish national registries. The children's EF were assessed with the Behavior Rating Inventory of Executive Functions questionnaire rated by primary caregivers and teachers. According to primary caregiver assessments, FHR-SZ children displayed widespread EF impairments and had an odds ratio of 3.7 (2.0-6.9) of having clinically significant global EF impairments compared to controls. FHR-BP children were most severely impaired regarding EF related to emotional control and had an odds ratio of 2.5 (1.2-5.1) of clinically significant global EF impairments compared to controls. Teacher assessments were overall comparable to primary caregiver assessments but teachers rated more difficulties in the FHR-SZ group than primary caregivers. Already at age 7, children with a parental history of SZ or BP displayed significant impairments of EF in everyday-life situations. FHR-SZ children displayed widespread significant impairments of EF, whereas FHR-BP children were most severely impaired on emotional control. Clinicians should be aware of potential EF impairments in FHR children.

The Danish High Risk and Resilience Study--VIA 7--a cohort study of 520 7-year-old children born of parents diagnosed with either schizophrenia, bipolar disorder or neither of these two mental disorders.

BACKGROUND: Severe mental illnesses like schizophrenia and bipolar disorder are known to be diseases that to some extent, but not entirely can be understood genetically. The dominating hypothesis is that these disorders should be understood in a neurodevelopmental perspective where genes and environment as well as gene-environment-interactions contribute to the risk of developing the disease. We aim to analyse the influences of genetic risk and environmental factors in a population of 520 7-year-old children with either 0, 1 or 2 parents diagnosed with schizophrenia spectrum psychosis or bipolar disorder on mental health and level of functioning. We hypothesize that a larger proportion of children growing up with an ill parent will display abnormal or delayed development, behavioural problems or psychiatric symptoms compared to the healthy controls. METHODS/DESIGN: We are establishing a cohort of 5207 year old children and both their parents for a comprehensive investigation with main outcome measures being neurocognition, behaviour, psychopathology and neuromotor development of the child. Parents and children are examined with a comprehensive battery of instruments and are asked for genetic material (saliva or blood) for genetic analyses. The participants are recruited via Danish registers to ensure representativity. Data from registers concerning social status, birth complications, somatic illnesses and hospitalization are included in the database. Psychological and relational factors like emotional climate in the family, degree of stimulation and support in the home and attachment style are also investigated. DISCUSSION: Data collection started January 1, 2013, and is successfully ongoing. By Aug 2015 424 families are included. About 20% of the invited families decline to participate, equal for all groups.

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. The Danish High Risk and Resilience Study - VIA 7 is a population-based cohort study. This study focuses on parents diagnosed with schizophrenia (n = 148), their co-parents (n = 157), parents with bipolar disorder (n = 98), their co-parents (n = 89) and control parents (n = 359). The Affective Lability Scale - short form (ALS-SF) was used to measure affective lability. We found significantly higher levels of affective lability in parents with schizophrenia and bipolar disorder compared with controls, but no significant differences between bipolar disorder and schizophrenia. Co-parents to parents with schizophrenia had significantly higher levels of affective lability compared to controls. Our results add to the existing knowledge concerning underlying transdiagnostic factors and nonrandom mating in schizophrenia and bipolar disorder and highlight the need for studies of parental affective lability as a potential risk factor for offspring in families with parental schizophrenia or bipolar disorder.

Development of social functioning in preadolescent children at familial high-risk of schizophrenia or bipolar disorder - a 4-year follow-up study from age 7 to 11.

Social functioning is a major indicator of psychosis risk and evidence is lacking regarding social functioning development during preadolescence in children at familial high risk of schizophrenia (FHR-SZ) or bipolar disorder (FHR-BP). We aimed to investigate development of social functioning from age 7 to 11 in children at FHR-SZ or FHR-BP compared with population-based controls. At 4-year follow-up, 179 children at FHR-SZ (mean age 12.0 y, SD 0.3), 105 children at FHR-BP (mean age 11.9 y, SD 0.2), and 181 controls (mean age 11.9 y, SD 0.2) participated. We used the Vineland-II to measure social functioning. Development of social functioning was non-significantly different across groups on the Socialization Composite score as well as the subscales Interpersonal Relations, Play and Leisure, and Coping Skills. At 4-year follow-up, children at FHR-SZ demonstrated impaired social functioning, whereas children at FHR-BP displayed social functioning comparable to controls except from impaired coping skills. From age 7 to 11, the maturational pace of social functioning in children at FHR-SZ and FHR-BP is parallel to that of controls. Children at FHR-SZ show stable social functioning deficits, whereas children at FHR-BP show normal social functioning except from emergence of discretely impaired coping skills at age 11.

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. The neurocognitive assessment covered intelligence, processing speed, attention, visuospatial and verbal memory, working memory, and set-shifting. Psychotic experiences were assessed through face-to-face interviews with the primary caregiver and the child. STUDY RESULTS: Set-shifting impairments at age 7 were associated with greater risk of psychotic experiences from age 7 to 11 in children at FHR-SZ. Children at FHR-BP and PBC showed no differential associations. Working memory and visuospatial memory impairments were related to increased risk of psychotic experiences across the cohort. However, adjusting for concurrent psychopathology attenuated these findings. CONCLUSIONS: Early childhood neurocognitive impairments are risk markers of middle childhood psychotic experiences, of which impaired set-shifting appears to further increase the risk of psychotic experiences in children at FHR-SZ. More research is needed to examine longitudinal associations between neurocognitive impairments and psychotic experiences in FHR samples.

A study of the genetic architecture of social responsiveness in families with parental schizophrenia or bipolar disorder and population-based controls.

Twin-studies of social responsiveness have reported moderate to high heritabilities, but studies using parent-child data are lacking. Additionally, social impairments have been suggested as a vulnerability marker for schizophrenia and bipolar disorder, but the heritability of social responsiveness in this context is unknown. This study is part of the Danish High Risk and Resilience Study - VIA, comprising families with one parent with schizophrenia (n = 202) or bipolar disorder (n = 120) and population-based controls (PBC, n = 200). Social responsiveness was assessed with The Social Responsiveness Scale, Second Edition (SRS-2). Heritability was estimated from variance components, and a polygenic risk score (PRS) for autism spectrum disorder (ASD) was calculated to assess the genetic relationship between ASD and SRS-2. SRS-2 heritability was moderate to high and significantly different from zero in all groups when the children were rated by the primary caregiver. With teacher ratings, the heritability was lower and only significant in the full cohort and PBC. We found no significant association between SRS-2 and PRS for ASD. Our study confirms that social responsiveness is heritable, but that heritability estimates are affected by the child-respondent relation and familial risk of mental illness. This has implications for clinical practice and research using SRS-2 and provides insight on the familial transmission of mental illness.

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. The cohort consists of 11-year-old children with at least one parent with schizophrenia (n = 179) or bipolar disorder (n = 105) and population-based controls (PBC, n = 181). Children and parents were assessed with The Social Responsiveness Scale, Second Edition. Duration of time each parent and child have lived together was ascertained through interviews. Parents with schizophrenia and parents with bipolar disorder exhibited poorer social responsiveness compared with PBC parents. Parents with schizophrenia displayed poorer social responsiveness compared with parents with bipolar disorder. Schizophrenia co-parents exhibited poorer social responsiveness compared with bipolar co-parents and PBC co-parents. We found significant positive associations between parents' and children's social responsiveness, with no interaction effect of duration of time living together. Considering that social impairments are suggested as a vulnerability marker, this knowledge calls for increased attention towards vulnerable families, particularly those where both parents have social impairments.

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. STUDY DESIGN: Latent profile analysis was used to identify subgroups at two assessments (age 7 and 11) based on the performance of 320 children at FHR-SZ or FHR-BP across eight neurocognitive functions. Temporal stability in subgroup membership was evaluated with latent profile transition analysis. Population-based controls (age 7, n = 199; age 11, n = 178) were included as a reference group. Children transitioning to a more impaired subgroup were compared with nontransitioning children on sex, FHR-status, global functioning, and psychopathology. STUDY RESULTS: At both assessment points, we identified three subgroups based on neurocognitive performance: a moderately-severely impaired, a mildly impaired, and an above-average subgroup. A total of 12.8% of children transitioned to a different subgroup, of which the majority (85.2%) moved to a more impaired subgroup. Parental diagnosis of schizophrenia, but neither parental diagnosis of bipolar disorder, global functioning at age 7, psychopathology, nor sex significantly differentiated children transitioning to a more impaired subgroup from nontransitioning children. CONCLUSIONS: During pre-adolescence, neurocognitive developmental lag is associated with being at FHR-SZ. Close attention to these children's neurocognitive development is indicated.

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. STUDY RESULTS: We included 85 (44% female) FHR-SZ, 63 (52% female) FHR-BP and 98 (50% female) PBC in the analyses. Executive control effects, caused by the spatial visuomotor conflict, showed no differences between groups. Bayesian ANOVA of reaction time (RT) variability, quantified by the coefficient of variation (CVRT), revealed a group effect with similarly higher CVRT in FHR-BP and FHR-SZ compared to PBC (BF10 = 6.82). The fMRI analyses revealed no evidence for between-group differences in task-related brain activation. Post hoc analyses excluding children with psychiatric illness yielded same results. CONCLUSION: FHR-SZ and FHR-BP at age 11-12 show intact ability to resolve a spatial visuomotor conflict and neural efficacy. The increased variability in RT may reflect difficulties in maintaining sustained attention. Since variability in RT was independent of existing psychiatric illness, it may reflect a potential endophenotypic marker of risk.

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. Methods: Self-reported Tanner stage (mean age 11.9, range 10.87-12.67), sex hormone levels, home environment, placement out of home, and problem behavior including psychiatric diagnoses of children at familial high-risk (FHR) of schizophrenia (FHR-SZ), bipolar disorder (FHR-BP) and population-based controls (PBC) were assessed. Results: A total of 465 children participated in the study (Tanner assessment N = 417, sex hormones N = 293). Assessed with self-reported Tanner, no difference in pubertal timing was found between groups (p = 0.09). Hormone levels did not differ between groups except for inhibin B (mean (SD) = 55.86 (29.13) pg/mL for FHR-SZ girls vs 84.98 (47.98) pg/mL) for PBC girls (p < 0.001)) and for follicle stimulating hormone (FSH) (mean (SD) = 5.82 (1.45) U/L for FHR-BP girls vs 4.54 (1.68) U/L for PBC girls (p < 0.001)). FHR children who were placed out of home (17 children, 3.8% of participants) had higher Tanner stages than those living at home (p < 0.001). Timing was not associated with level of problem behavior or psychiatric diagnoses. Conclusions: FHR children did not differ from controls in pubertal timing. Early life adversity assessed as placement out of home may be associated with accelerated pubertal timing among children of parents with schizophrenia or bipolar disorder.

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). Social responsiveness was measured with the Social Responsiveness Scale (SRS-2), completed by teachers and primary caregivers. ToM was measured using The Animated Triangles Task (ATT). Both SRS-2 and ATT were applied at age 7 and 11. A total of 520 children participated (FHR-SZ, n = 201; FHR-BP, n = 119; PBC, n = 200). Results showed no significant time by group interactions. At follow-up, children at FHR-SZ exhibited impaired social responsiveness compared with PBC regardless of the informant. At both timepoints, a higher proportion of children at FHR-SZ were rated at a clinically significant level, implying inference in everyday social interactions. Compared with PBC, primary caregivers reported impairments in social responsiveness in children at FHR-BP at follow-up. The three groups did not differ in ToM at follow-up. Social responsiveness and ToM do not develop differently in children at FHR-SZ, FHR-BP and PBC from age 7 to 11, but impairments in social responsiveness remain stable and may constitute a vulnerability marker particularly in children at FHR-SZ, but also FHR-BP. ToM abilities seem to improve and remain intact, but ToM development and ToM task properties should be taken into consideration.

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. Method: The Danish High Risk and Resilience Study VIA 7 is a population-based cohort study of children of parents diagnosed with schizophrenia (N = 202), bipolar disorder (N = 120) and controls (N = 200). We conducted a semi-structured anamnestic interview with the child's primary caregiver to assess early risk factors from pregnancy to age four. We used the Children's Global Assessment Scale to measure level of functioning at age seven. Results: 13 out of 17 risk factors were more prevalent in children at familial high risk for schizophrenia and 7 out of 17 risk factors were more prevalent in children at familial high risk for bipolar disorder compared to controls. Level of functioning decreased 2.7 (95% CI, 2.2; 3.3)-points per risk factor, but the association was not significantly different across the three groups (p = 0.09). Conclusions: Our results showed that children at age seven with familial high risk for schizophrenia or bipolar disorder experience a greater number of early risk factors. A higher number of early risk factors were associated with lower level of functioning at age seven. However, the association is not different for children with familial high risk or controls.

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. Here, we investigated whether partner resemblance for schizophrenia and bipolar disorder is influenced by assortative mating using polygenic risk scores (PRSs). METHODS: PRSs from The Danish High-Risk and Resilience Study-VIA 7 were compared between parents in three subsamples: population-based control parent pairs (N=198), parent pairs where at least one parent had schizophrenia (N=193), and parent pairs where at least one parent had bipolar disorder (N=115). RESULTS: The PRS for schizophrenia was predictive of schizophrenia in the full sample and showed a significant correlation between parent pairs (r=0.121, p=0.0440), indicative of assortative mating. The PRS for bipolar disorder was also correlated between parent pairs (r=0.162, p=0.0067), but it was not predictive of bipolar disorder in the full sample, limiting the interpretation. CONCLUSIONS: Our study provides genetic evidence for assortative mating for schizophrenia, with important implications for our understanding of the genetics of schizophrenia.

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. RESULTS: Three neurocognitive subgroups were derived: A Mildly Impaired (30%), Typical (51%), and Above Average subgroup (19%). The Mildly Impaired subgroup significantly underperformed controls (Cohen d = 0.11-1.45; Ps < 0.001) except in set-shifting (P = .84). FHR-SZ children were significantly more prevalent in the Mildly Impaired subgroup; FHR-BP children were more so in the Above Average subgroup (X2 (2, N = 315) = 9.64, P < .01). 79.7% FHR-BP and 64.6% FHR-SZ children demonstrated typical or above average neurocognitive functions. Neurocognitive heterogeneity related significantly to concurrent functioning, psychopathology severity, home environment adequacy, and polygenic scores for schizophrenia (Ps <. 01). Compared with controls, FHR-SZ and FHR-BP children had a 93% (RR, 1.93; 95% CI, 1.40-2.64) and 8% (RR, 1.08; 95% CI, 0.71-1.66) increased risk of Mildly Impaired subgroup membership. LIMITATIONS: Limitations include the cross-sectional design and smaller FHR-BP sample size. CONCLUSIONS: Identification of neurocognitive heterogeneity in preadolescent children at FHR-BP or FHR-SZ may ease stigma and enable pre-emptive interventions to enhance neurocognitive functioning and resilience to mental illness in the impaired sub-population.

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). Children and both parents were assessed using identical, age-relevant neurocognitive tests of intelligence, verbal working memory, and processing speed. RESULTS: In multiple regression analyses children's intelligence, verbal working memory, and processing speed scores were significantly associated with the corresponding parental cognitive function score. All associations from parents to offspring across functions were non-significant. No significant parental cognitive function by group interaction was observed. CONCLUSION: Transmissions of intelligence, processing speed, and verbal working memory from parents to offspring are function specific. The structure of transmission is comparable between families with schizophrenia, families with bipolar disorder and families without these disorders.

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. Design, Setting, and Participants: The Danish High Risk and Resilience Study is a prospective, longitudinal, cohort study that collected data from January 1, 2013, to January 31, 2016 (phase 1), and from March 1, 2017, to June 30, 2020 (phase 2). Data were collected at 2 university hospitals in Denmark, and participants included 520 children at FHR of schizophrenia or bipolar disorder along with a PBC group matched with the group of children at FHR of schizophrenia by age, sex, and municipality. Exposures: Parental schizophrenia, bipolar disorder, or neither. Main Outcomes and Measures: Neurocognitive functioning was assessed with validated tests of intelligence, processing speed, attention, memory, verbal fluency, and executive functioning. Multilevel mixed-effects linear regression models with maximum likelihood estimation were used to estimate neurocognitive development from age 7 to 11 years. Results: At 4-year follow-up, a total of 451 children (mean [SD] age; 11.9 [0.2] years; 208 girls [46.1%]) underwent neurocognitive testing. There were a total of 170 children at FHR of schizophrenia (mean [SD] age, 12.0 [0.3]; 81 girls [47.7%]), 103 children at FHR of bipolar disorder (mean [SD] age, 11.9 [0.2] years; 45 girls [43.7%]), and 178 children in the PBC group (mean [SD] age, 11.9 [0.2] years; 82 girls [46.1%]). At either age 7 or 11 years or at both assessments, 520 children participated in the neurocognitive assessment and were therefore included in the analyses. When correcting for multiple comparisons, no statistically significant time × group interactions were observed across the 3 groups. Compared with the PBC group at 4-year follow-up, children at FHR of schizophrenia showed significant neurocognitive impairment in 7 of 24 neurocognitive measures (29.2%; Cohen d range, 0.29-0.37). Compared with children at FHR of bipolar disorder, children at FHR of schizophrenia had significant neurocognitive impairment in 5 of 24 measures (20.8%; Cohen d range, 0.29-0.38). Children at FHR of bipolar disorder and those in the PBC group did not differ significantly. Conclusions and Relevance: In this cohort study, findings suggest that neurocognitive maturation was comparable across groups of children at FHR of schizophrenia or bipolar disorder compared with PBCs from age 7 to 11 years. Compared with the PBC group, children at FHR of schizophrenia demonstrated widespread, stable, neurocognitive impairments during this period, whereas children at FHR of bipolar disorder showed no neurocognitive impairments, which may indicate distinct neurodevelopmental pathways in children at FHR of schizophrenia and bipolar disorder.

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. METHODS: In a longitudinal population-based cohort study children at FHR-SZ (N=170), FHR-BP (N=103), and the control group (N=174) were assessed for psychotic experiences and axis I disorders with face-to-face interviews in early and middle childhood (at 7 and 11 years of age). RESULTS: Psychotic experiences were more prevalent in children at FHR-SZ (31.8%, odds ratio 2.1, 95% CI 1.3-3.4) than in the control group (18.4%) in middle childhood. Early childhood psychotic experiences predicted mental disorders in middle childhood after adjusting for early childhood disorders and familial risk (odds ratio 2.0, 95% CI 1.2-3.1). Having three or more psychotic experiences increased odds the most (odds ratio 2.5, 95% CI 1.1-5.7). Persistent psychotic experiences were associated with increased odds of middle childhood disorders (odds ratio 4.1, 95% CI 2.1-8.4). Psychotic experiences were nondifferentially associated with mental disorders across the three familial risk groups. CONCLUSIONS: Early childhood psychotic experiences predict mental disorders in middle childhood. Psychotic experiences index vulnerability for psychopathology nondifferentially in children at familial high risk and the control group. Psychotic experiences should be included in mental health screenings including children at familial high risk.

The Danish High-Risk and Resilience Study-VIA 15 - A Study Protocol for the Third Clinical Assessment of a Cohort of 522 Children Born to Parents Diagnosed With Schizophrenia or Bipolar Disorder and Population-Based Controls.

Background: Children born to parents with severe mental illness have gained more attention during the last decades because of increasing evidence documenting that these children constitute a population with an increased risk of developing mental illness and other negative life outcomes. Because of high-quality research with cohorts of offspring with familial risk and increased knowledge about gene-environment interactions, early interventions and preventive strategies are now being developed all over the world. Adolescence is a period characterized by massive changes, both in terms of physical, neurologic, psychological, social, and behavioral aspects. It is also the period of life with the highest risk of experiencing onset of a mental disorder. Therefore, investigating the impact of various risk and resilience factors in adolescence is important. Methods: The Danish High-Risk and Resilience Study started data collection in 2012, where 522 7-year-old children were enrolled in the first wave of the study, the VIA 7 study. The cohort was identified through Danish registers based on diagnoses of the parents. A total of 202 children had a parent diagnosed with schizophrenia, 120 children had a parent diagnosed with bipolar disorder, and 200 children had parents without these diagnoses. At age 11 years, all children were assessed for the second time in the VIA 11 study, with a follow-up retention rate of 89%. A comprehensive assessment battery covering domains of psychopathology, neurocognition, social cognition and behavior, motor development and physical health, genetic analyses, attachment, stress, parental functioning, and home environment was carried out at each wave. Magnetic resonance imaging scans of the brain and electroencephalograms were included from age 11 years. This study protocol describes the third wave of assessment, the VIA 15 study, participants being 15 years of age and the full, 3-day-long assessment battery this time including also risk behavior, magnetoencephalography, sleep, and a white noise paradigm. Data collection started on May 1, 2021. Discussion: We will discuss the importance of longitudinal studies and cross-sectional data collection and how studies like this may inform us about unmet needs and windows of opportunity for future preventive interventions, early illness identification, and treatment in the future.