Familial High Risk Of Schizophrenia Research Articles

Exploring the relationship between attributional style measured in virtual reality and bullying among children at familial high risk of schizophrenia or bipolar disorder compared with controls

BackgroundChildren of parents with severe mental illness report bullying more often compared with controls. We hypothesized that deviations in attributional styles may explain the increased prevalence of bullying experiences. We aimed to assess real-time responses to standardized ambiguous social situations, bullying experiences by children, their primary caregivers, and teachers, and to investigate potential associations between attributional styles and bullying. MethodThe study included 465 children aged 11–12, born to parents with schizophrenia, N =179, bipolar disorder, N = 105, or population-based controls, N = 181. Attributional style was evaluated using virtual reality environments depicting ambiguous social everyday situations. We created a tailored assessment since no suitable assessments were found. Bullying was assessed through self-reports and reports from primary caregivers and teachers. ResultsWe observed no group differences in the attributional style of the children. Reports from children, primary caregivers, and teachers revealed that compared with controls, children born to parents with schizophrenia were more likely to perceive bullying victimization, with high consistency among reports. No associations were found between bullying reports and attributional style. ConclusionsChildren of parents with schizophrenia consistently experienced more bullying, as reported by the children themselves, primary caregivers, and teachers. No differences in attributional style were found, indicating that attributional style did not explain the increased prevalence of bullying reports. While it cannot be ruled out that our virtual environments were insufficient to trigger a sense of social exclusion, the results suggest that the observed differences in reported bullying are genuine and not a result of the child's attributional style.

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

Impaired executive control is a potential prognostic and endophenotypic marker of schizophrenia (SZ) and bipolar disorder (BP). Assessing children with familial high-risk (FHR) of SZ or BP enables characterization of early risk markers and we hypothesize that they express impaired executive control as well as aberrant brain activation compared to population-based control (PBC) children. Using a flanker task, we examined executive control together with functional magnetic resonance imaging (fMRI) in 11- to 12-year-old children with FHR of SZ (FHR-SZ) or FHR of BP (FHR-BP) and PBC children as part of a register-based, prospective cohort-study; The Danish High Risk and Resilience study-VIA 11. We included 85 (44% female) FHR-SZ, 63 (52% female) FHR-BP and 98 (50% female) PBC in the analyses. Executive control effects, caused by the spatial visuomotor conflict, showed no differences between groups. Bayesian ANOVA of reaction time (RT) variability, quantified by the coefficient of variation (CVRT), revealed a group effect with similarly higher CVRT in FHR-BP and FHR-SZ compared to PBC (BF10 = 6.82). The fMRI analyses revealed no evidence for between-group differences in task-related brain activation. Post hoc analyses excluding children with psychiatric illness yielded same results. FHR-SZ and FHR-BP at age 11-12 show intact ability to resolve a spatial visuomotor conflict and neural efficacy. The increased variability in RT may reflect difficulties in maintaining sustained attention. Since variability in RT was independent of existing psychiatric illness, it may reflect a potential endophenotypic marker of risk.

Functional connectivity in people at clinical and familial high risk for schizophrenia

Patients diagnosed with schizophrenia (SZ) exhibit compromised functional connectivity within extensive brain networks. However, the precise development of this impairment during disease progression in the clinical high-risk (CHR) population and their relatives remains unclear. Our study leveraged data from 128 resting electroencephalography (EEG) channels acquired from 30 SZ patients, 21 CHR individuals, 17 unaffected healthy relatives (RSs; those at heightened SZ risk due to family history), and 31 healthy controls (HCs). These data were harnessed to establish functional connectivity patterns. By calculating the geometric distance between EEG sequences, we unveiled local and global nonlinear relationships within the entire brain. The process of dimensionality reduction led to low-dimensional representations, providing insights into high-dimensional EEG data. Our findings indicated that CHR participants exhibited aberrant functional connectivity across hemispheres, whereas RS individuals showcased anomalies primarily concentrated within hemispheres. In the realm of low-dimensional analysis, RS participants' third-dimensional occipital lobe values lay between those of the CHR individuals and HCs, significantly correlating with scale scores. This low-dimensional approach facilitated the visualization of brain states, potentially offering enhanced comprehension of brain structure, function, and early-stage functional impairment, such as occipital visual deficits, in RS individuals before cognitive decline onset.

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

BackgroundChildren 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. MethodsSelf-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. ResultsA 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. ConclusionsFHR children did not differ from controls in pubertal timing. Early life adversity assessed as placement out of home may be associated with accelerated pubertal timing among children of parents with schizophrenia or bipolar disorder.

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

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

Children at Familial High risk of Schizophrenia and Bipolar Disorder Exhibit Altered Connectivity Patterns During Pre-attentive Processing of an Auditory Prediction Error.

Individuals with schizophrenia or bipolar disorder have attenuated auditory mismatch negativity (MMN) responses, indicating impaired sensory information processing. Computational models of effective connectivity between brain areas underlying MMN responses show reduced connectivity between fronto-temporal areas in individuals with schizophrenia. Here we ask whether children at familial high risk (FHR) of developing a serious mental disorder show similar alterations. We recruited 67 children at FHR for schizophrenia, 47 children at FHR for bipolar disorder as well as 59 matched population-based controls from the Danish High Risk and Resilience study. The 11-12-year-old participants engaged in a classical auditory MMN paradigm with deviations in frequency, duration, or frequency and duration, while we recorded their EEG. We used dynamic causal modeling (DCM) to infer on the effective connectivity between brain areas underlying MMN. DCM yielded strong evidence for differences in effective connectivity among groups in connections from right inferior frontal gyrus (IFG) to right superior temporal gyrus (STG), along with differences in intrinsic connectivity within primary auditory cortex (A1). Critically, the 2 high-risk groups differed in intrinsic connectivity in left STG and IFG as well as effective connectivity from right A1 to right STG. Results persisted even when controlling for past or present psychiatric diagnoses. We provide novel evidence that connectivity underlying MMN responses in children at FHR for schizophrenia and bipolar disorder is altered at the age of 11-12, echoing findings that have been found in individuals with manifest schizophrenia.

Attachment representations in 7-year-old children at familial high risk of schizophrenia or bipolar disorder: Associations with mental disorders and daily functioning: The Danish High Risk and Resilience Study, VIA 7-A population-based cohort study.

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. 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. 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. 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.

Suicidal Ideation and Non-Suicidal Self-Injury Following Early Childhood Psychotic Experiences in Preadolescent Children at Familial High Risk of Schizophrenia or Bipolar Disorder-The Danish High Risk and Resilience Study, VIA 11.

Suicide is a leading cause of death in youth and is often preceded by suicidal ideation (SI) and non-suicidal self-injury (NSSI). Identifying early markers of risk for SI and NSSI could improve timely identification of at-risk individuals. Children (mean age 11.9, SD 0.2) at familial high risk of schizophrenia (N = 171), or bipolar disorder (N = 104), and controls (N = 174) were assessed for psychotic experiences (PE), SI, NSSI, and Axis I mental disorders in face-to-face interviews in early and middle childhood (age 7 and 11). Having 2 types of early childhood PE predicted middle childhood SI after accounting for previous SI, NSSI, and mental disorders (OR 2.8, 95% CI 1.1-6.9; P = .03). Two PE predicted NSSI (OR 3.0, 95% CI 1.2-7.7; P = .02) in excess of previous SI, NSSI, mental disorders, and familial risk. Persistent and incident PE predicted SI (OR 3.2, 95% CI, 1.1-8.8; P = .03; OR 3.8, 95% CI, 1.3-11.5; P = .02) in the fully adjusted model. Nineteen percent of children with persistent PE reported middle childhood SI vs 3.8% of those who never reported PE. In children with early childhood mental disorders, those who reported 2 PE had 4.4-fold increased odds of later SI (95% CI, 1.2-16.7; P = .03) after adjustments. PE were nondifferentially associated with outcomes across familial risk groups. Early childhood PE index elevated risk for subsequent SI and NSSI beyond what can be attributed to presence of mental disorders. Mental health screenings and clinical assessments should include early childhood PE.

Working memory heterogeneity from age 7 to 11 in children at familial high risk of schizophrenia or bipolar disorder– The Danish High Risk and Resilience Study

BackgroundDespite the genetic overlap between bipolar disorder and schizophrenia, working memory impairments are mainly found in children of parents with schizophrenia. However, working memory impairments are characterized by substantial heterogeneity, and it is unknown how this heterogeneity develops over time. We used a data-driven approach to assess working memory heterogeneity and longitudinal stability in children at familial high risk of schizophrenia (FHR-SZ) or bipolar disorder (FHR-BP). MethodsBased on the performances on four working memory tasks by 319 children (FHR-SZ, N = 202, FHR-BP, N = 118) measured at age 7 and 11, latent profile transition analysis was used to test for the presence of subgroups, and the stability of subgroup membership over time. Population-based controls (VIA 7, N = 200, VIA 11, N = 173) were included as a reference group. The working memory subgroups were compared based on caregiver- and teacher ratings of everyday working memory function, and dimensional psychopathology. ResultsA model with three subgroups characterized by different levels of working memory function (an impaired subgroup, a mixed subgroup, and an above average subgroup) best fitted the data. The impaired subgroup had the highest ratings of everyday working memory impairments and psychopathology. Overall, 98 % (N = 314) stayed in the same subgroup from age 7 to 11. ConclusionPersistent working memory impairments are present in a subset of children at FHR-SZ and FHR-BP throughout middle childhood. Attention should be given to these children, as working memory impairments influence daily life, and may serve as a vulnerability marker of transition to severe mental illness.

Hair cortisol concentrations and daily life stress in 7-year-old children at familial high-risk of schizophrenia or bipolar disorder. The Danish High Risk and Resilience Study – VIA 7

BackgroundDysregulation 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). MethodsA 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. ResultsSeven-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. ConclusionsChildren 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.

The development in rating-based executive functions in children at familial high risk of schizophrenia or bipolar disorder from age 7 to age 11: the Danish high risk and resilience study.

Executive functions (EF) deficits are well documented in children at familial high risk of schizophrenia (FHR-SZ), and to a lesser degree in children at familial high risk of bipolar disorder (FHR-BP). The aim of this study was to assess EF development in preadolescent children at FHR-SZ, FHR-BP and population-based controls (PBC) using a multi-informant rating scale. A total of 519 children (FHR-SZ, n = 201; FHR-BP, n = 119; PBC, n = 199) participated at age 7, at age 11 or at both time points. Caregivers and teachers completed the Behavior Rating Inventory of Executive Functions (BRIEF). The developmental pattern from age 7 to age 11, did not differ between groups. At age 11, caregivers and teachers rated children at FHR-SZ as having widespread EF deficits. A higher proportion of children at FHR-SZ had clinically significant scores on the General executive composite (GEC) and all BRIEF indices compared to PBC. According to the caregivers, children at FHR-BP had significantly more EF deficits than PBC on 9 out of 13 BRIEF scales, whereas according to teachers, they only had significantly more deficits on one subdomain (Initiate). Likewise, caregivers rated a significantly higher proportion of children at FHR-BP above the clinical cut-off on the GEC and Metacognition index, compared to PBC, whereas there were no significant differences according to teachers. This study highlights the relevance of including multi-informant rating scales in the assessment of EF in children at FHR-SZ and FHR-BP. The results imply a need to identify children at high risk who would benefit from targeted intervention.

Associations between exposure to early childhood adversities and middle childhood psychotic experiences in children at familial high risk of schizophrenia, bipolar disorder, and population-based controls: The Danish high risk and resilience study - VIA 7 and VIA 11.

Exposure to adversities in early childhood is associated with psychotic experiences and disorders in adulthood. We aimed to examine whether early childhood adversities are associated with middle childhood psychotic experiences in a cohort of children at familial high risk of schizophrenia (FHR-SZ), bipolar disorder (FHR-BP) and population-based controls (controls). Four hundred and forty-six children from The Danish High Risk and Resilience Study - VIA7 and VIA11 participated in this study (FHR-SZ = 170; FHR-BP = 103; controls = 173). Exposure to early childhood adversities and psychotic experiences were assessed using face-to-face interviews. Having childhood adversities assessed at baseline (age 7) was used as predictor. Psychotic experiences assessed at follow-up (age 11) were used as outcome. Across the sample, exposure to early childhood interpersonal adversities was associated with an increased risk for any middle childhood psychotic experiences and subclinical delusions when adjusting for relevant confounders (OR 1.8, 95% CI 1.0-3.1, p = 0.05; OR 3.0, 95% CI 1.6-5.6, p < 0.001). There was no significant dose-response effect of exposure to multiple types of childhood adversities on any psychotic experiences. There were no interaction effects between early childhood adversities and FHR on middle childhood psychotic experiences. Exploratory analyses revealed that experiencing domestic violence in early childhood was associated with any middle childhood psychotic experiences (OR 2.8, 95% CI 1.5-5.1, p = 0.001). Exposure to interpersonal adversities during early childhood is associated with an increased risk for middle childhood psychotic experiences including specifically subclinical delusions. Future studies should examine associations between exposure to childhood adversities and conversion to psychosis within this cohort.

Impaired motor development in children with familial high risk of schizophrenia or bipolar disorder and the association with psychotic experiences: a 4-year Danish observational follow-up study

Motor abnormalities have clinical relevance as a component of psychotic illness; they are not only a proxy of altered neurodevelopment, but also intimately related to psychotic risk. We aimed to assess motor development and its association with psychotic experiences in children with familial high risk (FHR) of schizophrenia or bipolar disorder compared with controls. The Danish High Risk and Resilience Study is a prospective longitudinal cohort study, for which participants were extracted from Danish registers. Children born in Denmark between Sept 1, 2004, and Aug 31, 2009, with no, one, or two parents born in Denmark with schizophrenia or bipolar disorder, could be included in the study. No ethnicity data were collected. Children with no biological parent diagnosed with schizophrenia spectrum disorder or bipolar disorder were matched to children with FHR of schizophrenia (one or two parents with schizophrenia spectrum disorder) on the basis of sex, age, and municipality. Children with FHR of bipolar disorder (one or two parents with bipolar disorder) were included as a non-matched group. We assessed motor function in children with FHR of schizophrenia, children with FHR of bipolar disorder, and children in the control group at approximately age 8 years (baseline; 2013-16) and age 12 years (follow-up; 2017-20) using the Movement Assessment Battery for Children-Second Edition (Movement ABC-2). Psychotic experiences were assessed using the psychosis section of the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version. Raters were masked regarding familial risk status. Motor development from baseline to follow-up in the different groups was assessed using a linear mixed model. Logistic regression examined the relationship between definite motor problems (≤5th percentile on Movement ABC-2) and psychotic experiences. Between March 1, 2017, and June 30, 2020, we studied 437 children (234 [54%] boys, 203 [46%] girls; mean age 11·99 years [SD 0·26, range 11·08-12·86]). Children with FHR of schizophrenia showed stable motor developmental deficits in manual dexterity (difference in intercept -1·62 [95% CI -2·39 to -0·85], p<0·0001; difference in slope 0·17 [-0·48 to 0·81], p=0·61) and balance (difference in intercept -1·58 [-2·34 to -0·82], p<0·0001; difference in slope 0·32 [-0·34 to 0·99], p=0·34), and a developmental lag in aiming and catching (difference in slope -1·07 [-1·72 to -0·41], p=0·0015; difference in intercept -0·59 [-1·35 to 0·17], p=0·13) compared with controls. Children with FHR of bipolar disorder showed no motor developmental differences on a group basis. Compared with controls, children with FHR of schizophrenia were more likely to have definite motor problems (odds ratio [OR] 2·86 [95% CI 1·60 to 5·11], p=0·0004), as were children with FHR of bipolar disorder (OR 2·45 [1·28 to 4·70], p=0·0068). Children with definite motor problems across all groups were more likely (OR 1·90 [1·12 to 3·21, p=0·017] to have had psychotic experiences than children with no definite motor problems. Clinicians should be aware that motor impairment in childhood can reflect neurodevelopmental vulnerability to psychosis. Our findings contribute to the identification of early risk markers for severe mental illness, both for use by clinicians and for establishing a basis for future primary preventive intervention studies in the premorbid phase. The Independent Research Fund Denmark, the Mental Health Services of the Capital Region of Denmark, the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus University, the Beatrice Surovell Haskell Fund, the Tryg Foundation, and the Innovation Fund Denmark. For the Danish translation of the abstract see Supplementary Materials section.

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

Familial high-risk (FHR) studies examining longitudinal associations between neurocognition and psychotic experiences are currently lacking. We hypothesized neurocognitive impairments at age 7 to be associated with increased risk of psychotic experiences from age 7 to 11 in children at familial high risk of schizophrenia (FHR-SZ) or bipolar disorder (FHR-BP) and population-based controls (PBC), and further, impaired functioning in some neurocognitive functions to be associated with greater risk of psychotic experiences in children at FHR-SZ or FHR-BP relative to PBC. Neurocognition was assessed at age 7 (early childhood) and psychotic experiences from age 7 to 11 (middle childhood) in 449 children from the Danish High Risk and Resilience Study. The neurocognitive assessment covered intelligence, processing speed, attention, visuospatial and verbal memory, working memory, and set-shifting. Psychotic experiences were assessed through face-to-face interviews with the primary caregiver and the child. Set-shifting impairments at age 7 were associated with greater risk of psychotic experiences from age 7 to 11 in children at FHR-SZ. Children at FHR-BP and PBC showed no differential associations. Working memory and visuospatial memory impairments were related to increased risk of psychotic experiences across the cohort. However, adjusting for concurrent psychopathology attenuated these findings. Early childhood neurocognitive impairments are risk markers of middle childhood psychotic experiences, of which impaired set-shifting appears to further increase the risk of psychotic experiences in children at FHR-SZ. More research is needed to examine longitudinal associations between neurocognitive impairments and psychotic experiences in FHR samples.

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

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

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. 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. 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. 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.

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

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. 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). 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. 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.

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

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. 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. 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. 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.

Jumping to Conclusions and Its Associations With Psychotic Experiences in Preadolescent Children at Familial High Risk of Schizophrenia or Bipolar Disorder-The Danish High Risk and Resilience Study, VIA 11.

The jumping to conclusions (JTC) bias, ie, making decisions based on inadequate evidence, is associated with psychosis in adults and is believed to underlie the formation of delusions. Knowledge on the early manifestations of JTC and its associations with psychotic experiences (PE) in children and adolescents is lacking. Preadolescent children (mean age 11.9 y, SD 0.2) at familial high risk of schizophrenia (FHR-SZ, n = 169) or bipolar disorder (FHR-BP, n = 101), and controls (n = 173) were assessed with the Beads Task to examine JTC. The number of beads drawn before making a decision, "draws to decision" (DTD) was used as a primary outcome. PE were ascertained in face-to-face interviews. General intelligence was measured with Reynolds Intellectual Screening Test. Children at FHR-SZ took fewer DTD than controls (4.9 vs 5.9, Cohen's d = 0.31, P = .004). Differences were attenuated when adjusting for IQ (Cohen's d = 0.24, P = .02). Higher IQ was associated with a higher number of DTD (B = 0.073, P < .001). Current subclinical delusions compared with no PE were associated with fewer DTD in children at FHR-SZ (P = .04) and controls (P < .05). Associations between delusions and DTD were nullified when accounting for IQ. JTC marks familial risk of psychosis in preadolescence, not reducible to general intelligence. JTC is associated with subclinical delusions, but this may be an expression of intellectual impairment. Future studies should establish temporality between JTC and delusion formation and examine JTC as a target for early intervention.

Mismatch negativity and P3a amplitude in children with familial high risk of schizophrenia or bipolar disorder – A Danish register-based EEG study

BackgroundInfrequent deviants in a rapid sequence of sounds elicit a negative cortical potential over the frontocentral midline (mismatch negativity, MMN) followed by a positive deflection (P3a). Both cortical potentials are consistently attenuated in patients with schizophrenia (SZ), and, to a lesser degree, in patients with bipolar disorder (BP). ObjectiveSince it is unclear when MMN and P3a deficits arise relative to the emergence of symptoms, we examined whether MMN and P3a alterations are already detectable in children with familial high risk. MethodsUsing 128-channel electroencephalography, we recorded auditory MMN and P3a evoked by a deviation in sound duration, frequency, or both in 51 children with familial high-risk for SZ (FHR-SZ), 41 children with familial high-risk for BP (FHR-BP), and 39 population-based children (PBC) at a mean age of 12.10. ResultsMMN amplitude evoked by a duration deviant was larger in children with FHR-BP compared to PBC and FHR-SZ. P3a amplitude in response to a duration ∗ frequency deviant was larger in children with FHR-BP compared to children with FHR-SZ, but not compared to PBC. MMN- and P3a-peak latency did not differ between groups. ConclusionsAt an age of around 12 years, children with FHR-BP display enhanced neural sensitivity to change detection of duration deviants, while FHR-SZ showed a normal response pattern. Longitudinal recordings in high-risk children during adolescence are required to elucidate the temporal trajectories of MMN and P3a responses and how they relate to the emergence of first clinical symptoms in SZ and BP.