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.

BACKGROUND AND HYPOTHESIS: 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. STUDY DESIGN: 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). STUDY RESULTS: 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. CONCLUSIONS: 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.

Childhood trauma in children at familial high risk of schizophrenia or bipolar disorder: A longitudinal study. The Danish High Risk and Resilience Study - VIA 7 and VIA 11.

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.

Development of visual attention from age 7 to age 12 in children with familial high risk for schizophrenia or bipolar disorder.

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.

Odor identification in 7-year-old children at familial high risk of schizophrenia or bipolar disorder - the Danish high risk and resilience study VIA 7.

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.

Psychopathology in 7-year-old children with familial high risk of developing schizophrenia spectrum psychosis or bipolar disorder - The Danish High Risk and Resilience Study - VIA 7, a population-based cohort study.

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.