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Published on: December 2, 2015
Neurocognitive Development in Children at Familial High Risk of Schizophrenia or Bipolar Disorder
Christina Bruun Knudsen1,2,3, Nicoline Hemager2,4,5, Aja Neergaard Greve1,2
1Psychosis Research Unit, Aarhus University Hospital-Psychiatry, Aarhus, Denmark.
Insights
Children at familial high risk (FHR) of schizophrenia showed stable neurocognitive impairments from ages 7 to 11. Those at FHR of bipolar disorder did not differ from controls, suggesting distinct neurodevelopmental pathways.
Area of Science:
- Child and Adolescent Psychiatry
- Neurodevelopmental Disorders
- Genetics and Mental Health
Background:
- Neurocognitive impairments are observed in children with familial high risk (FHR) for schizophrenia and bipolar disorder.
- Understanding preadolescent neurocognitive development is crucial for identifying shared and distinct pathways in these at-risk groups.
Purpose of the Study:
- To assess neurocognitive development from age 7 to 11 in children at FHR of schizophrenia or bipolar disorder compared to population-based controls (PBC).
Main Methods:
- A prospective, longitudinal cohort study in Denmark involving 520 children (FHR of schizophrenia, FHR of bipolar disorder, PBC).
- Neurocognitive functions assessed using validated tests (intelligence, processing speed, attention, memory, verbal fluency, executive functioning).
- Multilevel mixed-effects linear regression models analyzed neurocognitive development from age 7 to 11.
Main Results:
- No significant time × group interactions in neurocognitive development were observed across the three groups.
- Children at FHR of schizophrenia showed significant neurocognitive impairments compared to PBCs (7/24 measures) and compared to FHR bipolar disorder (5/24 measures).
- Children at FHR of bipolar disorder did not differ significantly from the PBC group in neurocognitive outcomes.
Conclusions:
- Neurocognitive maturation from age 7 to 11 was comparable between children at FHR of schizophrenia or bipolar disorder and PBCs.
- Widespread, stable neurocognitive impairments were observed in children at FHR of schizophrenia during this period.
- The absence of neurocognitive impairments in children at FHR of bipolar disorder suggests distinct neurodevelopmental trajectories compared to those at FHR of schizophrenia.
Importance:
Neurocognitive impairments exist in children at familial high risk (FHR) of schizophrenia and bipolar disorder. Studies on preadolescent developmental courses of neurocognition are important to describe shared and distinct neurodevelopmental pathways in these groups.
Objective:
To assess the development in specific neurocognitive functions from age 7 to 11 years in children at FHR of schizophrenia or bipolar disorder compared with children in a population-based control (PBC) group.
Design, Setting, And Participants:
The Danish High Risk and Resilience Study is a prospective, longitudinal, cohort study that collected data from January 1, 2013, to January 31, 2016 (phase 1), and from March 1, 2017, to June 30, 2020 (phase 2). Data were collected at 2 university hospitals in Denmark, and participants included 520 children at FHR of schizophrenia or bipolar disorder along with a PBC group matched with the group of children at FHR of schizophrenia by age, sex, and municipality.
Exposures:
Parental schizophrenia, bipolar disorder, or neither.
Main Outcomes And Measures:
Neurocognitive functioning was assessed with validated tests of intelligence, processing speed, attention, memory, verbal fluency, and executive functioning. Multilevel mixed-effects linear regression models with maximum likelihood estimation were used to estimate neurocognitive development from age 7 to 11 years.
Results:
At 4-year follow-up, a total of 451 children (mean [SD] age; 11.9 [0.2] years; 208 girls [46.1%]) underwent neurocognitive testing. There were a total of 170 children at FHR of schizophrenia (mean [SD] age, 12.0 [0.3]; 81 girls [47.7%]), 103 children at FHR of bipolar disorder (mean [SD] age, 11.9 [0.2] years; 45 girls [43.7%]), and 178 children in the PBC group (mean [SD] age, 11.9 [0.2] years; 82 girls [46.1%]). At either age 7 or 11 years or at both assessments, 520 children participated in the neurocognitive assessment and were therefore included in the analyses. When correcting for multiple comparisons, no statistically significant time × group interactions were observed across the 3 groups. Compared with the PBC group at 4-year follow-up, children at FHR of schizophrenia showed significant neurocognitive impairment in 7 of 24 neurocognitive measures (29.2%; Cohen d range, 0.29-0.37). Compared with children at FHR of bipolar disorder, children at FHR of schizophrenia had significant neurocognitive impairment in 5 of 24 measures (20.8%; Cohen d range, 0.29-0.38). Children at FHR of bipolar disorder and those in the PBC group did not differ significantly.
Conclusions And Relevance:
In this cohort study, findings suggest that neurocognitive maturation was comparable across groups of children at FHR of schizophrenia or bipolar disorder compared with PBCs from age 7 to 11 years. Compared with the PBC group, children at FHR of schizophrenia demonstrated widespread, stable, neurocognitive impairments during this period, whereas children at FHR of bipolar disorder showed no neurocognitive impairments, which may indicate distinct neurodevelopmental pathways in children at FHR of schizophrenia and bipolar disorder.
