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

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., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

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., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Background: Attachment quality may affect psychological functioning. However, evidence on attachment representations and their correlates in children born to parents with schizophrenia and bipolar disorder is sparse., Methods: We compared attachment representations in a Danish sample of 482 children aged 7 years at familial high risk of schizophrenia, bipolar disorder, and population-based controls and examined associations between attachment and mental disorders and daily functioning. Attachment representations were examined with the Story Stem Assessment Profile (SSAP). Mental disorders were ascertained in diagnostic interviews. Daily functioning was assessed with the Children's Global Assessment Scale., Results: We found no between-group differences in attachment. Higher levels of secure attachment were associated with decreased risk of concurrent mental disorders in the schizophrenia high-risk group. Higher levels of insecure and disorganized attachment were associated with increased risk of mental disorders across the cohort. Higher levels of secure and insecure attachment were associated with better and poorer daily functioning, respectively. In the current study, results regarding defensive avoidance could not be reported due to methodological limitations., Conclusion: Familial high risk of schizophrenia (FHR-SZ) or bipolar disorder is not associated with less secure or more insecure attachment at age 7. Insecure and disorganized attachment representations index risk of mental disorders and poorer functioning. Secure attachment may be a protective factor against mental disorders in children at FHR-SZ. Validation of the SSAP is needed., (© 2023 Scandinavian Psychological Associations and John Wiley & Sons Ltd.)

This study investigates indicators of disorganized caregiving among caregivers of children who have a familial predisposition of schizophrenia spectrum psychosis (SZ) or bipolar disorder (BP), and whether indicators of disorganized caregiving are associated with the caregivers' and children's level of functioning as well as the children's internalizing and externalizing behavior problems. Indicators of disorganized caregiving were assessed with the Caregiving Helplessness Questionnaire (CHQ). Level of functioning was evaluated using the Children's Global Assessment Scale and the Personal and Social Performance Scale, while dimensional psychopathology were measured with the Child Behavior Checklist. 185 caregivers belonging to a SZ combined group (i.e., SZ-I + SZ co-caregiver), 110 caregivers to a BP combined group (i.e., BP-I + BP co-caregiver), and 184 caregivers to a population-based control group provided data on CHQ. Having a history of SZ or BP or being a co-caregiver to a parent with SZ or BP was associated with higher levels of experiences of helplessness and fear. Higher scores on helplessness were associated with lower level of functioning among caregivers and children and with children having externalizing/internalizing behavior problems. These results emphasize the need for interventions addressing indicators of disorganized caregiving in families with SZ or BP.

Background: Dysregulation of the HPA-axis, perceived stress and interpersonal trauma are associated with an elevated risk for schizophrenia and bipolar disorder. Being at familial high-risk of these two mental disorders also constitutes an increased risk. In this study, we aimed to investigate hair cortisol concentrations and perceived stress among 7-year-old children at familial high-risk of schizophrenia (FHR-SZ), bipolar disorder (FHR-BP), and population-based controls (controls)., Methods: A total of 515 children (mean age 7.8, SD 0.2) from baseline assessment of the Danish High Risk and Resilience Study - VIA 7 participated in this study. Hair cortisol concentrations were analyzed among 322 children (FHR-SZ; N = 111, FHR-BP; N = 82, controls; N = 129). Perceived stress was assessed with the Daily Life Stressor Scale including 512 children (FHR-SZ; N = 195, FHR-BP; N = 118, controls; N = 199). Interpersonal trauma was measured with face-to-face interviews., Results: Seven-year-old children at FHR-SZ or FHR-BP did not have a higher level of hair cortisol concentrations compared with controls (FHR-SZ: mean: 5.10, 95%CI 3.69-6.52; FHR-BP: mean: 5.01, 95%CI 3.27-6.72; controls: mean: 4.51, 95%CI 3.61-5.40; p = 0.77). Self-reported perceived stress was higher among children at FHR-SZ and FHR-BP compared with controls (FHR-SZ: mean: 12.09, 95%CI 10.99-13.19; FHR-BP: mean: 10.69, 95%CI 9.38-11.99; controls: mean: 8.90, 95%CI 8.13-9.68; p < 0.001). There was no significant association between hair cortisol concentrations and perceived stress (p = 0.84). Exploratory analyses revealed that interpersonal trauma exposure was neither associated with elevated hair cortisol nor perceived stress., Conclusions: Children at FHR-SZ and FHR-BP did not exhibit higher levels of hair cortisol concentrations at age 7, while both FHR-groups had higher level of self-reported perceived stress compared with controls. Early attention to stress in children at FHR is crucial and these vulnerabilities should be targeted in future interventions studies., Competing Interests: Declaration of Competing Interest All authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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.

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., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

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., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

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., (© 2022. The Author(s).)

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., (© 2022 British Psychological Society.)

Objectives: Childhood trauma increases the risk of developing mental illness as does being born to parents with schizophrenia or bipolar disorder. We aimed to compare prevalence of lifetime childhood trauma among 11-year-old children at familial high risk of schizophrenia (FHR-SZ) or bipolar disorder (FHR-BP) compared with population-based controls (PBCs)., Design: The study is a longitudinal, prospective cohort study of children at FHR-SZ, FHR-BP, and PBCs., Methods: A cohort of 512 children at FHR-SZ (N = 199), FHR-BP (N = 118), and PBCs (N = 195) were examined at baseline (mean age 7.8, SD 0.2) and 451 children at FHR-SZ (N = 172), FHR-BP (N = 104), and PBCs (N = 175) were examined at four-year follow-up (mean age 11.9, SD 0.2, retention rate 87.3%). Childhood trauma was measured with a semi-structured interview., Results: Children at FHR-BP had an elevated risk of exposure to any lifetime trauma (age 0-11 years) compared with PBCs (OR 2.082, 95%CI 1.223-3.545, p = .007) measured with binary logistic regression. One-way ANOVA revealed that both FHR-groups had a higher lifetime prevalence of exposure to a greater number of types of trauma compared with PBCs (FHR-SZ: observed mean: 1.53, 95%CI 1.29-1.77; FHR-BP: observed mean: 1.56, 95%CI 1.26-1.85; PBCs: observed mean: 0.99, 95%CI 0.82-1.17; p < .001). Binary logistic regression showed that the lifetime risk of exposure to interpersonal trauma (age 0-11 years) was elevated for both FHR-groups (FHR-SZ: OR 3.773, 95%CI 2.122-6.710, p < .001; FHR-BP: OR 3.602, 95%CI 1.913-6.783, p < .001)., Conclusions: Children at FHR-SZ and FHR-BP are at increased risk for being exposed to childhood trauma compared with PBCs. This study underscores the need for early detection, support, and prevention of childhood trauma in children at FHR-SZ and FHR-BP., (© 2022 The British Psychological Society.)

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.

Background: Children at familial high-risk of schizophrenia and bipolar disorder have an elevated prevalence of mental disorders but studies of children within a narrow age range are lacking and there are few conjoint studies of these two groups. Knowledge on their mental health is important for prevention and early intervention., Methods: The authors examined mental disorders and global functioning in children at familial high-risk of schizophrenia (FHR-SZ) and bipolar disorder (FHR-BP) compared with population-based controls. In a longitudinal cohort study, 450 children (FHR-SZ, n = 171; FHR-BP, n = 104; controls, n = 175), were assessed for Axis I disorders at baseline and four-year follow-up (mean age 11.9, SD 0.2) with the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children and for global functioning with Children's Global Assessment Scale., Results: Cumulative incidence of Any Axis I disorder was elevated by age 11 in children at FHR-SZ (54.4%, OR 3.0, 95% CI 1.9-4.7, p < .001) and children at FHR-BP (52.9%, OR 2.8, 95% CI 1.7-4.7, p < .001) compared with controls (28.6%). Children at FHR-SZ and FHR-BP had higher rates of affective disorders (OR 4.4, 95% CI 1.4-13.5, p = .009; OR 5.1, 95% CI 1.6-16.4, p = .007), anxiety disorders (OR 2.1, 95% CI 1.1-4.0, p = .02; OR 3.0, 95% CI 1.5-6.1, p = .002), and stress and adjustment disorders (OR 3.3, 95% CI 1.4-7.5, p = .006; OR 5.3, 95% CI 2.2-12.4, p < .001). Disruptive behavior disorders (OR 2.8, 95% CI 1.0-7.3, p = .04) and ADHD (OR 2.9, 95% CI 1.6-5.3, p < .001) were elevated in children at FHR-SZ. Both FHR groups had lower global functioning than controls. Cumulative incidence of disorders increased equally across the three groups from early childhood to preadolescence and level of functioning did not change differentially., Conclusions: Children at FHR-SZ and FHR-BP have an elevated prevalence of mental disorders and poorer functioning than controls. Vulnerability in children at FHR manifests early and remains stable throughout childhood. Early attention toward their mental health and identification of those in need of intervention is warranted., (© 2021 Association for Child and Adolescent Mental Health.)

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.

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., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

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., (© 2021. Springer-Verlag GmbH, DE part of Springer Nature.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Spang, Thorup, Ellersgaard, Hemager, Christiani, Burton, Gantriis, Greve, Gregersen, Mors, Nordentoft, Jepsen, Obel and Plessen.)

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 (X 2 (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., (Copyright © 2022 Elsevier B.V. All rights reserved.)

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., (© 2022. The Author(s).)

Objective: Children with familial high-risk of schizophrenia (FHR-SZ) or bipolar disorder (FHR-BP) are frequently affected in a range of domains known to be precursors of severe mental illness. No previous studies have gathered known precursors to examine whether they distribute evenly across familial high risk (FHR) children or if they cluster among a smaller group. Since such examination holds the potential to identify high and low risk of severe mental illness groups, we aimed to cluster FHR and control children affected to various degrees., Method: In The Danish High Risk and Resilience Study VIA 7, a clinical cohort study, 514 7-year-old children with FHR-SZ or FHR-BP and matched controls were assessed in domains of motor function, neurocognition, emotional control, behavior, social cognition, self-perception, language, psychotic experiences, and psychopathology, and grouped using cluster analysis. Associations between clusters and parents' level of education, functioning, caregiver status, child's level of stimulation and support in the home, and polygenic risk scores were examined., Results: A total of four groups including one of broadly affected children were identified. The broadly affected group was represented 4-5-fold (18.1%) amongst FHR-SZ children and 2-3-fold (10.2%) amongst FHR-BP children, compared to controls (4.1%) ( P < .001), and the broadly affected group had lower levels of caregiver functioning ( P < .001) and stimulation and support at home ( P < .001)., Conclusion: Precursors of severe mental illness distribute unevenly among FHR children; while approximately half are not affected in any domains, the other half are affected to various degrees. Targeted support towards the affected groups is indicated., (© The Author(s) 2022. Published by Oxford University Press on behalf of the University of Maryland's school of medicine, Maryland Psychiatric Research Center.)

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., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

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. This study focus on parents diagnosed with schizophrenia (n = 150) or bipolar disorder (n = 100) and control parents (n = 182), as well as their partners without schizophrenia or bipolar disorder (n = 440). We used linear mixed-effect models, and main outcomes were mental disorders, intelligence, processing speed, verbal working memory, and social functioning. We found that parents having children by a partner with schizophrenia or bipolar disorder more often fulfilled the criteria for a mental disorder and had poorer social functioning compared to parents having children by a partner without schizophrenia or bipolar disorder. Furthermore, parents having children by a partner with schizophrenia performed poorer on processing speed compared to parents in the control group. The presence of nonrandom mating found in this study has implications for our understanding of familial transmission of these disorders and our findings should be considered in future investigations of potential risk factors for children with a parent with schizophrenia or bipolar disorder., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The cognitive control system matures gradually with age and shows age-related sex differences. To gain knowledge concerning error adaptation in familial high-risk groups, investigating error adaptation among the offspring of parents with severe mental disorders is important and may contribute to the understanding of cognitive functioning in at-risk individuals. We identified an observational cohort through Danish registries and measured error adaptation using an Eriksen flanker paradigm. We tested 497 7-year-old children with a familial high risk of schizophrenia (N = 192) or bipolar disorder (N = 116) for deficits in error adaptation compared with a control group (N = 189). We investigated whether error adaptation differed between high-risk groups compared with controls and sex differences in the adaptation to errors, irrespective of high-risk status. Overall, children exhibited post-error slowing (PES), but the slowing of responses did not translate to significant improvements in accuracy. No differences were detected between either high-risk group compared with the controls. Boys showed less PES and PES after incongruent trials than girls. Our results suggest that familial high risk of severe mental disorders does not influence error adaptation at this early stage of cognitive control development. Error adaptation behavior at age 7 years shows specific sex differences.

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. Potential associations to neurocognition, psychopathology, and the home environment were investigated., Results: Children at FHR-SZ or FHR-BP displayed intact decision making. Quality of decision making showed significant but weak cross-sectional associations to neurocognition and adequacy of the home environment. Associations to aspects of executive functions and the home environment differed across groups., Limitations: Due to the cross-sectional nature of this study, the predictive value of efficient and inefficient decision making remains to be investigated in planned follow-up studies of this cohort., Conclusions: Young children at FHR-SZ or FHR-BP do not differ from controls in decision making efficacy, which does not appear to be an early risk marker of bipolar disorder or schizophrenia. Decision making is weakly associated to neurocognition and the home environment, but not to general intelligence or psychopathology., (Copyright © 2020 Elsevier B.V. All rights reserved.)

We aimed to examine the prevalence of psychotic experiences (PEs) in children with familial high risk of schizophrenia (FHR-SZ) or bipolar disorder (FHR-BP) and, in exploratory analyses, to examine the possible associations between PEs and mental disorders as well as level of functioning. A cohort of seven-year-old children with FHR-SZ (N = 199), FHR-BP (N = 118) and controls (N = 196) was recruited through Danish nationwide registers. Lifetime PEs were assessed through interviews using the psychosis section of the 'Schedule for Affective Disorders and Schizophrenia for School-Age Children - Present and Lifetime Version' (K-SADS-PL). Lifetime DSM-IV diagnoses were ascertained through K-SADS-PL and the level of functioning of the children through 'Children's Global Assessment Scale'. Both children with FHR-SZ (OR = 2.9, 95% CI = 1.4-6.2, p = 0.005) and FHR-BP (OR = 2.9, 95% CI = 1.3-6.7, p = 0.011) had an increased risk of having experienced "severe" PEs compared with controls. In the overall cohort PEs were associated with any lifetime mental disorder, Attention-Deficit/Hyperactivity Disorder, anxiety disorders and a lower level of functioning. The findings of a higher proportion of high risk children reporting PEs could represent an early manifestation of later more severe psychopathology or simply an unspecific transitory symptom. Future follow-up studies of this cohort will explore the predictive value of the occurrence of PEs at age seven., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2020. Published by Elsevier B.V.)

Background: Children with familial high risk of schizophrenia (FHR-SZ) or bipolar disorder (FHR-BP) are at increased risk of developing similar disorders and show cognitive deficits during childhood. The aim of this paper is to investigate visual attention and its developmental trajectories in children with FHR-SZ and with FHR-BP to increase our knowledge about potential cognitive endophenotypes of these two disorders., Methods: We compared the performance of 89 children with FHR-SZ (N = 32), FHR-BP (N = 22), and population-based controls (PBC, N = 35) at age 7 to that at age 12 as well as including 133 12-year-old children with FHR-SZ (N = 50), FHR-BP (N = 43) and PBC (N = 40) to investigate visual attention, as part of the Danish High Risk and Resilience Study. We used the TVA-based whole report paradigm, based on the Bundesen's Theory of Visual Attention (TVA) to investigate visual attention., Results: Children with FHR-SZ that showed deficits in visual processing speed at age 7 improved to a level that was not significantly different from controls at age 12. All children improved over time. We found no attentional deficits in FHR children at age 12., Conclusions: On visual attention, children with FHR-SZ did not show developmental deficits or lags and, together with children with FHR-BP, they develop similarly to control children between age 7 to age 12. This emphasizes the potential of beneficial neuroplastic changes in cognitive deficits found at younger ages in children with FHR-SZ. It also highlights the importance of identifying and characterizing cognitive developmental trajectories of high-risk children and provides hope that visual attention may develop appropriately in these groups., Competing Interests: Declaration of competing interest HRS has received honoraria as speaker from Sanofi Genzyme, Denmark and Novartis, Denmark, as consultant from Sanofi Genzyme, Denmark and as senior editor (NeuroImage) and editor-in-chief (Neuroimage Clinical) from Elsevier Publishers, Amsterdam, The Netherlands. HRS has also received royalties as book editor from Springer Publishers, Stuttgart, Germany and Gyldendahl Publishers, Copenhagen, Denmark., (Copyright © 2021 Elsevier B.V. All rights reserved.)

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.

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.

Background: Odor identification deficits occur in individuals with schizophrenia and their unaffected first-degree relatives, while deficits are less pronounced in individuals with bipolar disorder. We hypothesized that children at familial high-risk for schizophrenia (FHR-SZ) show odor identification deficits compared to population-based controls and that children at familial high-risk for bipolar disorder (FHR-BP) perform intermediate., Methods: Odor identification was assessed at age 7 in 184 children with FHR-SZ, 106 children with FHR-BP, and 186 population-based controls with the Brief Smell Identification Test. Dimensional and predefined categorical outcomes were used in the analyses. Potential relationships with psychopathological, cognitive, and home environmental variables were conducted using hierarchical and logistic multiple regression analyses., Results: ANOVA revealed no between-group differences in odor identification. Using the recommended cut-off (below 5), we found a significantly greater proportion of boys at FHR-SZ than population-based boys with an abnormal odor identification (p = .013). However, a supplementary analysis using a Danish-based cut-off (below 4) did not support this. All children showed significant, positive associations of odor identification with female gender, social responsiveness, and verbal working memory. Lower social responsiveness predicted abnormal odor identification in boys at FHR-SZ, only using the recommended cut-off., Conclusions: Odor identification efficacy and risk status appear independent in this early developmental phase. Using the recommended threshold, abnormal odor identification is more frequent in young boys at FHR-SZ than in population-based boys and is linked to lower social responsiveness. The validity of these results is questioned by non-significant differences in the rates when using an exploratory Danish-based threshold., Competing Interests: Declaration of competing interest There are no conflicts of interest for any of the authors., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Attention deficits are found in children at familial high risk of schizophrenia (FHR-SZ) and bipolar disorder (FHR-BP) using assessment methods relying on motor-based response latency. This study compares visual attention functions in children at FHR-SZ or FHR-BP with controls using an unspeeded task unconfounded by motor components., Methods: Visual attention was assessed in 133 7-year-old children at FHR-SZ (N = 56) or FHR-BP (N = 32), and controls (N = 45) using the unspeeded paradigm, TVA-based whole report. We compared four parameters of visual attention: visual processing speed, visual short-term memory, threshold for visual perception, and error rate. Further, we investigated their potential relationships with severity of psychopathology, adequacy of the home environment, and neurocognitive measures., Results: Children at FHR-SZ displayed significant deficits in perceptual processing speed of visual attention compared with controls (p < .001; d = 0.75) as did children at FHR-BP (p < .05; d = 0.54). Visual processing speed was significantly associated with spatial working memory (β = -0.23; t(68) = -3.34, p = .01) and psychomotor processing speed (β = 0.14, t(67) = 2.11, p < .05)., Limitations: Larger group sizes would have permitted inclusion of more predictors in the search for neurocognitive and other factors associated with the parameters of TVA-based whole report., Conclusions: Young children at FHR-SZ and FHR-BP display significant deficits in processing speed of visual attention, which may reflect the effect of shared vulnerability risk genes. Early identification of children at FHR-SZ and FHR-BP with perceptual processing speed impairments may represent a low-cost basis for low-risk interventions., (Copyright © 2019. Published by Elsevier B.V.)

Objective: To characterize social cognition, language, and social behavior as potentially shared vulnerability markers in children at familial high-risk of schizophrenia (FHR-SZ) and bipolar disorder (FHR-BP)., Methods: The Danish High-Risk and Resilience Study VIA7 is a multisite population-based cohort of 522 7-year-old children extracted from the Danish registries. The population-based controls were matched to the FHR-SZ children on age, sex, and municipality. The FHR-BP group followed same inclusion criteria. Data were collected blinded to familial high-risk status. Outcomes were social cognition, language, and social behavior., Results: The analysis included 202 FHR-SZ children (girls: 46%), 120 FHR-BP children (girls: 46.7%), and 200 controls (girls: 46.5%). FHR-SZ children displayed significant deficits in language (receptive: d = -0.27, P = .006; pragmatic: d = -0.51, P < .001), social responsiveness (d = -0.54, P < .001), and adaptive social functioning (d = -0.47, P < .001) compared to controls after Bonferroni correction. Compared to FHR-BP children, FHR-SZ children performed significantly poorer on adaptive social functioning (d = -0.29, P = .007) after Bonferroni correction. FHR-BP and FHR-SZ children showed no significant social cognitive impairments compared to controls after Bonferroni correction., Conclusion: Language, social responsiveness, and adaptive social functioning deficits seem associated with FHR-SZ but not FHR-BP in this developmental phase. The pattern of results suggests adaptive social functioning impairments may not be shared between FHR-BP and FHR-SZ in this developmental phase and thus not reflective of the shared risk factors for schizophrenia and bipolar disorder., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Given the partially shared genetic liability between schizophrenia and bipolar disorder, we aimed to assess whether 7-year-old children with a familial high risk of schizophrenia or bipolar disorder display specific deficits of sustained attention and interference control compared with each other and with control children., Methods: An observational cohort was identified through Danish registries and consisted of 522 children 7 years of age with no, one, or two parents with a diagnosis of schizophrenia or bipolar disorder. Control subjects were matched based on age, sex, and municipality. Sustained attention and interference control were assessed using Conners' Continuous Performance Test II and a modified Eriksen flanker task. Assessors were blinded to group membership of participants. The effect of higher genetic loading was not considered in the statistical models owing to low numbers., Results: At 7 years of age, children with a familial high risk of schizophrenia displayed deficits of sustained attention and subtle deficits in interference control compared with control children and children with a familial high risk of bipolar disorder. Children with a familial high risk of bipolar disorder displayed similar abilities of sustained attention and interference control as control children except in terms of a lower accuracy., Conclusions: Our findings suggest distinct neurodevelopmental characteristics in middle childhood of sustained attention and interference control for children of parents with schizophrenia or bipolar disorder., (Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Importance: Children at familial high risk of schizophrenia spectrum disorders (FHR-SZ) or bipolar disorder (FHR-BP) exhibit neurocognitive impairments. Large studies of neurocognition in young children at familial high risk at the same age are important to differentiate the pathophysiology and developmental trajectory of these 2 groups., Objective: To characterize neurocognitive functions in 7-year-old children with FHR-SZ or FHR-BP and a control population., Design, Setting, and Participants: This multisite population-based cohort study collected data from January 1, 2013, to January 31, 2016, in the first wave of the Danish High Risk and Resilience Study VIA 7 at 2 university hospital research sites in Copenhagen and Aarhus using Danish registries. Participants (n = 514) included 197 children with FHR-SZ, 118 with FHR-BP, and 199 controls matched with the FHR-SZ group for age, sex, and municipality. Assessors were blinded to risk status., Exposures: Parents with schizophrenia, bipolar disorder, or neither diagnosis., Main Outcomes and Measures: Neurocognitive functions were measured across 23 tests. Four neurocognitive domains were derived by principal component analysis, including processing speed and working memory, verbal functions, executive and visuospatial functions, and declarative memory and attention., Results: A total of 514 children aged 7 years were included in the analysis (46.3% girls), consisting of 197 children with FHR-SZ (46.2% girls), 118 with FHR-BP (46.6% girls), and 199 controls (46.2% girls). Children with FHR-SZ were significantly impaired compared with controls on processing speed and working memory (Cohen d = 0.50; P < .001), executive and visuospatial functions (Cohen d = 0.28; P = .03), and declarative memory and attention (Cohen d = 0.29; P = .02). Compared with children with FHR-BP, children with FHR-SZ performed significantly poorer in processing speed and working memory (Cohen d = 0.40; P = .002), executive and visuospatial functions (Cohen d = 0.35; P = .008), and declarative memory and attention (Cohen d = 0.31; P = .03). Children with FHR-BP and controls did not differ., Conclusions and Relevance: Children with FHR-SZ had widespread neurocognitive impairments, supporting the hypothesis of neurocognitive functions as endophenotypes of schizophrenia. The absence of neurocognitive deficits in children with FHR-BP suggests distinct neurodevelopmental manifestations in these familial high-risk groups at this age. Early detection of children with FHR-SZ and cognitive impairments is warranted to investigate associations of neurocognition with transition to psychosis, add to the knowledge of their developmental pathophysiology, and inform early intervention programs.

This study aimed to compare the psychopathological profiles of children at familial high risk of schizophrenia spectrum psychosis (FHR-SZ) or bipolar disorder (FHR-BP) with population-based controls. We used Danish nationwide registers to retrieve a cohort of 522 seven-year-old children of parents with schizophrenia spectrum psychosis (N=202), bipolar disorder (N=120) or none of these disorders (N=200). Psychopathology was assessed by reports from multiple informants, including children, parents and teachers. Lifetime DSM-IV diagnoses were ascertained by blinded raters through the Schedule for Affective Disorders and Schizophrenia for School-Age Children. The dimensional assessment of psychopathology was performed by the Child Behavior Checklist, the Teacher's Report Form, a modified version of the ADHD-Rating Scale, the Test Observation Form, and the State-Trait Anxiety Inventory for Children. Current level of functioning was evaluated using the Children's Global Assessment Scale (CGAS). The prevalence of lifetime psychiatric diagnoses was significantly higher in both FHR-SZ children (38.7%, odds ratio, OR=3.5, 95% confidence interval, CI: 2.2-5.7, p < 0.001) and FHR-BP children (35.6%, OR=3.1, 95% CI: 1.8-5.3, p < 0.001) compared with controls (15.2%). FHR-SZ children displayed significantly more dimensional psychopathology on all scales and subscales compared with controls except for the Anxious subscale of the Test Observation Form. FHR-BP children showed higher levels of dimensional psychopathology on several scales and subscales compared with controls, but lower levels compared with FHR-SZ children. Level of functioning was lower in both FHR-SZ children (CGAS mean score = 68.2; 95% CI: 66.3-70.2, p < 0.0001) and FHR-BP children (73.7; 95% CI: 71.2-76.3, p < 0.05) compared with controls (77.9; 95% CI: 75.9-79.9). In conclusion, already at the age of seven, FHR-SZ and FHR-BP children show a higher prevalence of a broad spectrum of categorical and dimensional psychopathology compared with controls. These results emphasize the need for developing early intervention strategies towards this vulnerable group of children., (© 2018 World Psychiatric Association.)

Background: Owing to the genetic overlap between schizophrenia and bipolar disorder, we aimed to assess domain-specific motor aberrations and disorder specificity among 7-year-old children with a familial risk of schizophrenia or bipolar disorder by comparing children in familial risk groups with each other and with children not in these risk groups., Methods: In the Danish High Risk and Resilience Study, we established a cohort of 7-year-old children with no, one, or two parents with schizophrenia or bipolar disorder in Denmark between Jan 1, 2013, and Jan 31, 2016. We matched children of parents diagnosed with schizophrenia to children of parents without schizophrenia on the basis of their home address, age, and sex. Even though we did not match children of parents with bipolar disorder directly to controls because of resource constraints, we only recruited children into the three groups who did not differ in terms of age, sex, and urbanicity. We investigated motor function in children using the Movement Assessment Battery for Children-Second Edition. Motor function raters were masked to participants' clinical risk status during assessments. We assessed the effects of familial risk group in a mixed-model analysis with repeated measures with an unstructured variance component matrix., Findings: We studied 514 children (198 [39%] children of parents with schizophrenia, 119 [23%] of parents with bipolar disorder, and 197 [38%] of parents without schizophrenia or bipolar disorder). Children of parents with schizophrenia showed impaired motor performance compared with those of parents without in the subdomains of manual dexterity (mean difference -1·42 [95% CI -2·08 to -0·77]; p<0·0001) and balance (-1·38 [-2·03 to -0·72]; p<0·0001), but not of aiming and catching (-0·39 [-0·97 to 0·19]; p=0·18). Children of parents with bipolar disorder did not show any significant difference in motor performance to children of parents without in the subdomains of manual dexterity (-0·69 [-1·44 to 0·07]; p=0·08), balance (-0·68 [-1·44 to 0·08]; p=0·08), and aiming and catching (-0·36 [-1·03 to 0·31]; p=0·29). Comparison of familial risk groups of mental disorders revealed no significant differences in the subdomains of manual dexterity (-0·74 [-1·49 to 0·02]; p=0·06), balance (-0·70 [-1·46 to 0·06]; p=0·07), or aiming and catching (-0·03 [-0·70 to 0·63]; p=0·92)., Interpretation: Motor abnormalities in children with a familial risk of schizophrenia are specific at 7 years of age with respect to fine motor function and balance, but non-specific with respect to familial risk of bipolar disorder. Clinicians should be aware of motor symptoms and refer children with definite motor problems (below the fifth percentile) to a child physiotherapist., Funding: Mental Health Services of the Capital Region of Denmark, Aarhus University, and the Lundbeck Foundation Initiative for Integrative Psychiatric Research., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Aim: The stability of delusional themes in psychotic disorders is only sparsely lit. The study aims to investigate the stability of delusional themes over a period of time in patients with first-episode non-affective psychosis., Methods: The data were drawn from a randomized controlled trial of 547 first-episode patients with schizophrenia spectrum disorders, the OPUS trial. A subsample of 411 patients met our inclusion criteria. They were interviewed at the time of first treatment contact, and at years 1, 2 and 5 after onset. The delusional themes of the 411 patients were classified by applying principal component analysis to the patients' scores on 12 items of delusions from the Scale for the Assessment of Positive Symptoms in Schizophrenia, SAPS. The course of the patients' predominant delusional themes was analysed afterwards., Results: The 12 delusional themes from SAPS were converted into five groups using principal component analysis. At all three follow ups there were almost equal proportions of patients with the predominant delusion being from the same group of delusional themes as at baseline and of patients with the predominant delusion being from another group of delusional themes than at baseline., Conclusions: The predominant delusional theme at the time of first treatment contact was seen to be only of some predictive value to the predominant delusional theme at the later follow-up points in patients with first-episode non-affective psychosis. This stresses the importance of a systematic assessment of different delusional themes in the continued monitoring of early signs of psychotic relapse and at each psychotic episode., (© 2013 Wiley Publishing Asia Pty Ltd.)