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. We assessed their performance within the domains of neurocognition, motor function, language, social cognition, social behavior, psychopathology, and home environment. RESULTS: FHR-SZ boys compared with FHR-SZ girls had a higher proportion of disruptive behavior and attention-deficit hyperactivity disorder (ADHD) and exhibited lower performance in manual dexterity, balance, and emotion recognition. No sex differences were found between boys and girls within FHR-BP group. Compared with controls, both FHR-SZ boys and FHR-SZ girls showed impaired processing speed and working memory, had lower levels of global functioning, and were more likely to live in an inadequate home environment. Compared with control boys, FHR-SZ boys showed impaired manual dexterity, social behavior, and social responsiveness, and had a higher proportion of ADHD and disruptive behavior disorder diagnoses. Stress and adjustment disorders were more common in FHR-BP boys compared with control boys. We found no differences between FHR-BP girls and control girls. CONCLUSIONS: Impairment within neurodevelopmental domains associated within FHR-SZ boys v. FHR-SZ girls was most evident among boys, whereas no sex differences were found within the FHR-BP group (FHR-BP boys v. FHR-BP girls). FHR-SZ boys exhibited the highest proportion of early developmental impairments.

Home environment of 11-year-old children born to parents with schizophrenia or bipolar disorder - a controlled, 4-year follow-up study: The Danish High Risk and Resilience Study - VIA 11.

BACKGROUND: The home environment has a major impact on child development. Parental severe mental illness can pose a challenge to the home environment of a child. We aimed to examine the home environment of children of parents with schizophrenia or bipolar disorder and controls longitudinally through at-home assessments. METHODS: Assessments were conducted within The Danish High Risk and Resilience Study, a nationwide multi-center cohort study of children of parents with schizophrenia or bipolar disorder and population-based controls. The level of at-home stimulation and support was measured at age 7 (N = 508 children) and age 11 (N = 430 children) with the semi-structured HOME Inventory. Results from the 11-year follow-up study were analyzed and compared with 7-year baseline results to examine change across groups. RESULTS: At age 11, children of parents with schizophrenia and bipolar disorder had lower levels of stimulation and support than controls (mean (s.d.) = 46.16 (5.56), 46.87 (5.34) and 49.25 (4.37) respectively, p < 0.001). A higher proportion of children with parental schizophrenia or bipolar disorder lived in inadequate home environments at age 11, compared with controls (N (%) = 24 (15.0), 12 (12.2) and 6 (3.5) respectively, p < 0.003). The changes in home environment scores did not differ across groups from age 7 to age 11. CONCLUSIONS: Assessed longitudinally from the children's age of 7 to 11, children of parents with schizophrenia or bipolar disorder had lower levels of stimulation and support in their homes than controls. Integrated support which can target practical, economic, social and health issues to improve the home environment is indicated.

Examining selection bias in a population-based cohort study of 522 children with familial high risk of schizophrenia or bipolar disorder, and controls: The Danish High Risk and Resilience Study VIA 7.

PURPOSE: Knowledge about representativity of familial high-risk studies of schizophrenia and bipolar disorder is essential to generalize study conclusions. The Danish High Risk and Resilience Study (VIA 7), a population-based case-control familial high-risk study, creates a unique opportunity for combining assessment and register data to examine cohort representativity. METHODS: Through national registers, we identified the population of 11,959 children of parents with schizophrenia (FHR-SZ) or bipolar disorder (FHR-BP) and controls from which the 522 children participating in The VIA 7 Study (202 FHR-SZ, 120 FHR-BP and 200 controls) were selected. Socio-economic and health data were obtained to compare high-risk groups and controls, and participants versus non-participants. Selection bias impact on results was analyzed through inverse probability weights. RESULTS: In the total sample of 11,959 children, FHR-SZ and FHR-BP children had more socio-economic and health disadvantages than controls (p < 0.001 for most). VIA 7 non-participants had a poorer function, e.g. more paternal somatic and mental illness (p = 0.02 and p = 0.04 for FHR-SZ), notifications of concern (FHR-BP and PBC p < 0.001), placements out of home (p = 0.03 for FHR-SZ), and lower level of education (p ≤ 0.01 for maternal FHR-SZ and FHR-BP, p = 0.001 for paternal FHR-BP). Inverse probability weighted analyses of results generated from the VIA Study showed minor changes in study findings after adjustment for the found selection bias. CONCLUSIONS: Familial high-risk families have multiple socio-economic and health disadvantages. In The VIA 7 Study, although comparable regarding mental illness severity after their child's birth, socioeconomic and health disadvantages are more profound amongst non-participants than amongst participants.

Intergenerational transmission of suicide attempt in a cohort of 4.4 million children.

BACKGROUND: The association between suicide attempts (SAs) in parents and children is unclear, and risk indicators for intergenerational transmission remain undocumented. We aimed to assess this association, considering the child's developmental period at the time of parents' attempted suicide, and the parental relation. METHODS: Using a prospective cohort design, nationwide population data were linked to the Psychiatric Central Register and National Patient Register for all individuals aged 10 years or older living in Denmark between 1980 and 2016. We assessed incidence rate ratios (IRRs) and cumulative hazards for children's first SA. RESULTS: In a cohort of 4 419 651 children, 163 056 (3.7%) had experienced a parental SA. An SA was recorded among 6996 (4.3%) of the exposed children as opposed to 70112 (1.6%) in unexposed individuals. Higher rates were noted when a parental SA occurred during early childhood (0 ⩽ age < 2) [IRR, 4.7; 95% confidence interval (CI) 4.2-5.4] v. late childhood (6 ⩽ age < 13) (IRR, 3.6; 95% CI 3.4-3.8) when compared to those unexposed. Children exposed prior to age 2 had the highest rates of all sub-groups when reaching age 13-17 (IRR, 6.5; 95% CI 6.0-7.1) and 18-25 years (IRR, 6.8; 95% CI 6.2-7.4). Maternal SA (IRR, 3.4; 95% CI 3.2-3.5) was associated with higher rates than paternal (IRR, 2.8; 95% CI 2.7-2.9). CONCLUSION: Parental SA was associated with children's own SA. Exposure during early developmental stages was associated with the highest rates. Early preventive efforts are warranted as is monitoring of suicide risk in the children from age 13.

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). We identified 48 genome-wide significant associations across several traits, of which 3 also survived our strict study-wide quality criteria. We additionally performed a functional annotation of implicated genes, as most of the 48 associations were with variants within protein-coding genes. In total, our study highlighted associations with five genes (TGM3, CACNB4, ANKS1B, CSMD1 and SYNE1) associated with measures of working memory, processing speed and social behavior. Our results thus identify novel associations, including previously unreported parent-of-origin associations with relevant genes, and our top results illustrate new potential gene → endophenotype → disorder pathways.

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.

Heterogeneity of social cognitive and language functions in children at familial high-risk of severe mental illness; The Danish High Risk and Resilience Study VIA 7.

Cognitive heterogeneity characterizes individuals with schizophrenia and bipolar disorder; however, little is known of cognitive heterogeneity within young children at familial high-risk of schizophrenia or bipolar disorder. This study aimed to investigate heterogeneity across social cognitive and language functions in children at familial high-risk of schizophrenia or bipolar disorder, i.e. severe mental illness (FHR-SMI). This may help designate subgroups in need of intervention initiatives. A data-driven, hierarchical cluster analysis was applied across a sample of 322 children at FHR-SMI (FHR-SZ, n = 200; FHR-BP, n = 120) on measures of Theory of Mind, facial emotion recognition, social cognitive processing speed, receptive and pragmatic language. We examined differences between subgroups as well as differences between subgroups and a control group. Exploratively, the subgroups were compared in terms of social responsiveness and global functioning. A Typical-High Functioning Subgroup with intact social cognitive and language functioning (34.5%), a Mildly Impaired Subgroup with selective impairments in explicit Theory of Mind and language functioning (58.7%), and a Significantly Impaired Subgroup with social cognitive and language functioning impairments (6.8%) were identified. The subgroups differed significantly from each other and overall compares to the controls. The Significantly and Mildly Impaired Subgroups presented with poorer social responsiveness and global functioning than the Typical-High Functioning Subgroup. In young children with FHR-SMI, three subgroups with relatively homogeneous social cognitive and language functioning profiles were observed. Only a small proportion of children at FHR-SMI displayed large social cognitive and language functioning impairments in middle childhood.

Parental mental illness, attendance at preventive child healthcare and dental caries in the offspring: a nation-wide population-based cohort study.

PURPOSE: Severe mental illness (SMI) may interfere with parental caregiving practices and offspring development. Adhering to preventive well-child visits and maintaining good oral hygiene during early childhood requires parental involvement. Whether these activities are affected by parental SMI is unclear. The purpose of the present study was to determine whether children exposed to parental SMI are at increased risk of non-attendance to preventive well-child visits and vaccinations at age 0-5 years and of child dental caries experience at age 5 years. Furthermore, interactions between maternal psychiatric and sociodemographic variables in relation to an adverse child outcome were assessed. METHODS: Data were obtained from national Danish health registers. All children born in Denmark between January 1997 and December 2010 were followed from birth until their 6th birthday. RESULTS: 679,339 children were included in the study (51% male). Of these, 49,059 children (7.8%) had at least one parent with a lifetime SMI diagnosis. Children of parents with SMI had elevated odds of missing well-child visits and vaccinations (OR 1.41; 95% CI 1.39-1.44, p < 0.0001), and of child dental caries (OR 1.58; 95% CI 1.55-1.62, p < 0.0001). In the presence of maternal SMI, low socioeconomic classification and single-mother status added more to the elevated risk than specific maternal diagnosis or timing of last psychiatric contact. CONCLUSION: Parents with SMI are less compliant with preventive child healthcare activities than parents without SMI. This indicates a need for practical support to these families in order to prevent inequality in health among their offspring.

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.

Quantitative genome-wide association analyses of receptive language in the Danish High Risk and Resilience Study.

BACKGROUND: One of the most basic human traits is language. Linguistic ability, and disability, have been shown to have a strong genetic component in family and twin studies, but molecular genetic studies of language phenotypes are scarce, relative to studies of other cognitive traits and neurodevelopmental phenotypes. Moreover, most genetic studies examining such phenotypes do not incorporate parent-of-origin effects, which could account for some of the heritability of the investigated trait. We performed a genome-wide association study of receptive language, examining both child genetic effects and parent-of-origin effects. RESULTS: Using a family-based cohort with 400 children with receptive language scores, we found a genome-wide significant paternal parent-of-origin effect with a SNP, rs11787922, on chromosome 9q21.31, whereby the T allele reduced the mean receptive language score by ~ 23, constituting a reduction of more than 1.5 times the population SD (P = 1.04 × 10-8). We further confirmed that this association was not driven by broader neurodevelopmental diagnoses in the child or a family history of psychiatric diagnoses by incorporating covariates for the above and repeating the analysis. CONCLUSIONS: Our study reports a genome-wide significant association for receptive language skills; to our knowledge, this is the first documented genome-wide significant association for this phenotype. Furthermore, our study illustrates the importance of considering parent-of-origin effects in association studies, particularly in the case of cognitive or neurodevelopmental traits, in which parental genetic data are not always incorporated.

Quality of life and self-esteem in 7-year-old children with familial high risk of schizophrenia or bipolar disorder: the Danish High Risk and Resilience Study-VIA 7-a population-based cohort study.

It is well established that children with familial high risk of schizophrenia (FHR-SZ) or bipolar disorder (FHR-BP) have a higher risk of developing mental disorders, however, little is known of to what degree the genetic and environmental vulnerabilities affect the quality of life and self-esteem of these children. We aimed to compare the quality of life and self-esteem between children with FHR-SZ or FHR-BP and controls. We used Danish nationwide registers to retrieve a cohort of 522 7-year-old children with FHR-SZ or FHR-BP and controls. Quality of life was assessed with the 'Health-related Quality of Life Screening Instrument', KIDSCREEN-27, and the scale 'Social Acceptance (Bullying)' from the KIDSCREEN-52. Self-esteem was assessed with the self-report scale 'I think I am'. Assessors were blind to familial risk status of the children. Children with FHR-SZ displayed lower levels of the general quality of life, as well as lower scores on the 'Psychological Well-being' scale and the 'School Environment' scale of the KIDSCREEN-27 compared with controls. Both children with FHR-SZ and FHR-BP reported more bullying victimization compared with controls. Children with FHR-SZ reported lower self-esteem on the total scale of 'I think I am', as well as on the 'Skills and talents', the 'Psychological well-being', and the 'Relationships with others' subscales compared with controls. The findings of lower quality of life and self-esteem in children with FHR-SZ together with more bullying victimization in both familial high-risk groups call for studies on low risk, early intervention strategies towards this group of vulnerable 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.

Post-traumatic Stress Disorder in School-age Children: A Nationwide Prospective Birth Cohort Study.

Traumatic childhood events are some of the few identifiable and to some extent preventable causes of psychiatric illness. Children exposed to severely stressful events may react with post-traumatic stress disorder (PTSD) and this may impact their level of function in daily life, their future development and mental health. The traumatic stress model suggests that traumatic stress in the family, community violence, and other traumas are regarded as additive environmental factors that can outweigh protective compensatory factors and thus interact with individual vulnerabilities. This study is based on prospective panel data including the whole population of children born in Denmark from 1984 to 1994, who are followed from age 7 to age 18 (N = 679,000) in the window between 2001 and 2012. Risk factors for first-time diagnose with PTSD are analyzed by the discrete time log-odd model. We found a lifetime prevalence of 2.3% PTSD in school-age children (n = 15,636). In accordance with the model, indicators of traumatic stress in the family, family disintegration, community violence, and individual vulnerabilities predicted later diagnose with PTSD. Individual neurodevelopmental disorder - especially autism (adjusted Odds Ratio (OR 7.1) and ADHD (OR 10.7) - were predicative of PTSD. The results cooperated the traumatic stress model. Some results were inconsistent with the traumatic stress model e.g., parental substance abuse were associated with less than expected PTSD in school-age children when adjusted for other risk factors. This indicates that PTSD may be underestimated in these groups. PTSD diagnoses in administrative records underestimate the prevalence, systematically. Efforts to increase PTSD screening may allow for better management.

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). We investigated the relationships between linguistic ability and motor function using correlation and regression analyses, focusing on developmental coordination disorder (DCD) and specific language impairment (SLI) and their potential associations with the three risk groups. RESULTS: We found significant correlations between most measures of language and motor function and significant associations of DCD and SLI with language and movement measures, respectively, the largest effect being that of DCD on receptive language, with a significant interaction effect: DCD was associated with poorer performance in children from schizophrenia families compared to bipolar disorder and control families. Both disorders showed higher prevalence among children with familial high risk of mental illness. We did not find significant evidence of genetic overlap between DCD and SLI. CONCLUSIONS: Our results suggest strong links between the domains of motor function and linguistic ability. Children of parents with schizophrenia are at high risk of comorbid language and movement disorders.

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. A population-based cohort of 522 children (parental SZ, n = 202; parental BP, n = 120; controls, n = 200) and their parents underwent the same assessment battery covering a wide range of cognitive functions. We used Bayesian statistics to model performance. We found that performance on non-verbal tests was better in offspring than parents with SZ or BP, using the controls as reference. However, for verbal tests, there was little to no evidence for this pattern or even some evidence for the opposite in the BP group: relatively better performance in parents than offspring. The findings suggest that the offspring of parents with SZ or BP may be particularly disadvantaged in verbal abilities. Future studies will show whether this pattern persists throughout development.

Family-based preventive intervention for children of parents with severe mental illness: A randomized clinical trial.

Background: Children of parents with a severe mental illness have an increased risk of developing a lifetime mental illness. We aimed to compare the effects of a preventive family-based intervention, VIA Family, with treatment as usual (TAU) on these children's global functioning. Methods: Between 2017 and 2021, we conducted a pragmatic, rater-blinded, two-arm parallel-group superiority trial in Denmark. Families with at least one child aged 6-12 years and at least one biological parent with schizophrenia spectrum disorder, bipolar disorder, or recurrent major or moderate depression were included. We randomly allocated 95 families with their 113 children to VIA Family or TAU (ratio 1:1). VIA Family was individually tailored and based on case management. The intervention included options for psychoeducation, parental support, and treatment for emerging child psychiatric symptoms. Blinded raters assessed children and their families at baseline and after 18 months. The primary outcome was the difference in change between groups at end-of-treatment in daily global functioning measured with the Children's Global Assessment Scale. Secondary outcomes were emotional and behavioral problems and days absent from school. We analyzed data blinded to allocation. Results: At post-intervention, differences in mean change from baseline between VIA Family and TAU were non-significant (CGAS: -1.20, 95% CI = -6.61; 4.21, p = 0.66), as were the differences on the secondary and exploratory outcomes. Conclusion: Contrary to our hypothesis, we did not find a superior effect of VIA Family compared with TAU. The short follow-up period and large sample heterogeneity might explain the null findings. Therefore, a possible long-term, preventive treatment effect has yet to be explored.

A study protocol for the randomized controlled trial SAFIR FAMILY TALK: a selective primary preventive intervention vs. service as usual for children of parents with mental illness.

BACKGROUND: Children of parents with mental illness have an increased risk of developing mental illness themselves throughout their lifespan. This is due to genetic factors but also environmental disadvantages during childhood associated with parental mental illness. Selective primary preventive interventions for the children are recommended to mitigate risk factors and strengthen protective factors, but large-scale, longitudinal studies are needed. This study aims to investigate the effect of the Family Talk Preventive Intervention in a cohort of children and their parents with mental illness. METHODS: The study is a randomized controlled trial with 286 planned families with at least one parent with any mental illness and at least one child aged 7 to 17 years. It will be carried out in the mental healthcare system in the Capital Region of Denmark. Families will be referred from hospitals and municipalities. The children and parents will be assessed at baseline and then randomized and allocated to either the Family Talk Preventive Intervention or service as usual. The intervention group will be assigned to Family Talk Preventive Intervention, a manualized programme consisting of ~ seven sessions for the family, including psychoeducation about parental mental illness and resilience in children, stimulating dialogue between family members and creating a common family narrative. The study period for both groups will be 12 months. Follow-up assessments will be conducted after 4 months and 12 months. The primary outcomes are the children's level of functioning, parental sense of competence and family functioning. DISCUSSION: Given the prevalence of transgenerational transmission of mental illness, a systematic approach to prevention is needed in the mental healthcare setting. This study provides valuable knowledge on the Family Talk Preventive Intervention with a large sample size, inclusion of any parental mental illness and examination of the primary outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT05615324. Registered on 26 October 2022. Retrospectively registered.

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.

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.

The Strengths and Difficulties Questionnaire Is of Clinical Significance Regarding Emotional and Behavioral Problems in 7-Year-Old Children With Familial Risk of Schizophrenia or Bipolar Disorder and Population-Based Controls the Danish High Risk and Resilience Study-VIA 7; A Population-Based Cohort Study.

Background: Children born to parents with severe mental illness are at increased risk of mental and behavioral difficulties during childhood. We aimed to investigate the occurrence of clinically significant behavioral difficulties in 7-year-old children of parents diagnosed with schizophrenia or bipolar disorder as well as in control children by using the Strengths and Difficulties Questionnaire (SDQ). Further, we aimed to determine if the SDQ could function as a screening instrument for clinically relevant behavioral problems of children at high risk of these severe mental illnesses. Methods: By means of the Danish National Registers, we established a cohort of 522 7-year old children stratified by familial high risk for schizophrenia spectrum disorder (N = 202), bipolar disorder (N =120), and controls (N = 200). The child's primary caregiver completed the SDQ parent version and the Child Behavior Checklist (CBCL) while the schoolteacher completed the SDQ teacher version and the CBCL teacher equivalent; the Teachers Report Form (TRF). Finally, global functioning was assessed with the Children's Global Assessment Scale (CGAS). Results: Children with familial high risk of schizophrenia spectrum disorder or bipolar disorder have a significantly increased risk (OR = 3.8 and 2.3) of suffering clinically significant behavioral difficulties at age 7-years according to SDQ parent ratings. The SDQ discriminates with moderate to high sensitivity and high specificity between familial high-risk children with and without a psychiatric diagnosis and has overall compelling discriminatory abilities in line with the more time consuming CBCL/TRF.Conclusions Familial high-risk children have more behavioral difficulties and more frequently at a level indicative of mental illness compared to control children as measured by the SDQ. The SDQ works well as a screening instrument for clinically relevant behavioral problems in high-risk children.