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