Neurocognitive profiles in early childhood in relation to clinical and functional outcomes in middle childhood in offspring at familial high-risk of schizophrenia or bipolar disorder: The Danish High-Risk and Resilience Study.

BACKGROUND: Widespread neurocognitive impairments exist in children at familial high-risk of schizophrenia (FHR-SZ), whereas evidence is mixed in children at FHR of bipolar disorder (FHR-BP). Neurocognitive heterogeneity is well-established, but associations with longitudinal clinical and functional outcomes remain unexplored. METHODS: In this prospective cohort study, 274 children (FHR-SZ, n = 170, FHR-BP, n = 104, 46.7% female, mean age 12.0 years, SD 0.25) provided neurocognitive data at baseline and clinical data at 4-year follow-up. The assessed neurocognitive functions included intelligence, processing speed, attention, memory, and executive functions. Axis I mental disorders, psychotic experiences, and functioning were ascertained through child and caregiver interviews. Dimensional psychopathology was reported by the caregiver. Three baseline neurocognitive subgroups (mildly impaired, typical, and above-average) derived from hierarchical cluster analysis across FHR-groups constituted categorical predictors with clinical and functional measures at follow-up as outcomes. RESULTS: Compared with children in the typical subgroup and after accounting for sex, outcome of interest and Any Axis I disorder at baseline, and FHR-group, children in the mildly impaired subgroup at baseline had a threefold increased risk of any externalizing mental disorder (OR 2.9, 95% CI 1.3-6.5, p = .007) and a twofold increased risk of psychotic experiences (OR 2.0, 95% CI 1.0-3.8, p = .04) during middle childhood. Additionally, they had significantly higher dimensional symptom severity (Cohen's d range 0.27-0.43, p < .05) and poorer global functioning (Cohen's d = 0.48, p < .001) at follow-up. Neurocognitive subgroup membership was non-differentially associated with clinical and functional outcomes across FHR-groups. CONCLUSIONS: A significantly impaired neurocognitive profile in early childhood confers risk for detrimental clinical and functional outcomes in middle childhood beyond that which can be attributed to pre-existing clinical and functional states and constitutes a cross-diagnostic, neurodevelopmental risk marker in these FHR-groups. Early neurocognitive profiling is warranted, and future studies should investigate long-term associations with mental disorders.