Neurocognitive Development in Children at Familial High Risk of Schizophrenia or Bipolar Disorder
Authors: Christina Bruun Knudsen, Nicoline Hemager, Aja Neergaard Greve, Rikke Lambek, Anna Krogh Andreassen, Lotte Veddum, Julie Marie Brandt, Maja Gregersen, Mette Falkenberg Krantz, Anne Søndergaard, Nanna Lawaetz Steffensen, Merete Birk, Henriette Brockdorff Stadsgaard, Jessica Ohland, Birgitte Klee Burton, Jens Richardt Møllegaard Jepsen, Anne Amalie Elgaard Thorup, Merete Nordentoft, Ole Mors, Vibeke Fuglsang Bliksted
Journal: JAMA Psychiatry (2022)

<h3>Importance</h3> 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. <h3>Objective</h3> 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. <h3>Design, Setting, and Participants</h3> 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. <h3>Exposures</h3> Parental schizophrenia, bipolar disorder, or neither. <h3>Main Outcomes and Measures</h3> 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. <h3>Results</h3> 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<i>d</i>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<i>d</i>range, 0.29-0.38). Children at FHR of bipolar disorder and those in the PBC group did not differ significantly. <h3>Conclusions and Relevance</h3> 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.