Cognitive reserve in seven-year-old children at familial high risk of schizophrenia or bipolar disorder.

Cognitive reserve (CR), referring to the brain's adaptability to maintain functioning despite pathology, has been found to positively impact the clinical manifestations in schizophrenia and bipolar disorder. Here, we aimed to explore the protective role of CR in children at familial high risk of schizophrenia (FHR-SZ) or bipolar disorder (FHR-BP) compared with population-based controls (PBC). This study is part of The Danish High Risk and Resilience Study, a cohort study of 522 seven-year-old children at FHR-SZ (n = 202, 45.6% females) or FHR-BP (n = 120, 46.1% females) and PBC (n = 200, 46.2% females). CR was assessed using principal component analysis including information about child IQ, school performance, peer relations, physical leisure activities, developmental milestones, parental education and occupation, and family leisure activities. Clinical outcomes included child global functioning, lifetime psychopathology, and psychotic experiences. Neurocognitive outcomes included processing speed, sustained attention, verbal memory, visuospatial memory, verbal working memory, and set-shifting. Compared with PBC, CR was lower in children at FHR-SZ (p < 0.001, d = 0.73) and FHR-BP (p < 0.001, d = 0.51). Additionally, children at FHR-SZ had lower CR than FHR-BP (p = 0.042, d = 0.24). Across groups, CR was non-differentially and positively associated with global functioning (p < 0.001) and all neurocognitive outcomes (p ≤ 0.005) and negatively associated with psychopathology (p ≤ 0.007) and delusional psychotic experiences (p = 0.019). Children at high risk have lower CR already at an early developmental stage. CR may serve as a protective factor against the development of psychopathology and neurocognitive impairments, offering a potential target in preventative interventions aiming at altering the long-term trajectories for high-risk populations.