Neurocognitive Development in Adolescent Offspring at Familial High Risk of Schizophrenia or Bipolar Disorder and a Population-Based Control Group.

Abstract

The course of neurocognitive development prior to the typical age of schizophrenia or bipolar disorder onset remains largely unexplored among offspring at familial high risk for these disorders. The authors sought to compare neurocognitive development in offspring at familial high risk of schizophrenia (FHR-SZ) or at familial high risk of bipolar disorder (FHR-BP) and a population-based control (PBC) group at ages 7, 11, and 15. This study examined neurocognitive development in offspring at FHR-SZ, at FHR-BP, and in a PBC group who participated in the Danish High Risk and Resilience Study, a prospective, nationwide cohort study. Participants were assessed at ages 7 (N=520), 11 (N=451), and 15 (N=396) using a comprehensive neurocognitive battery. Mixed-effects models evaluated group differences in developmental trajectories across domains including intelligence, processing speed, attention, memory, planning, verbal fluency, and set-shifting. Offspring at FHR-SZ showed a significant developmental lag in processing speed between ages 11 and 15 (β=-3.82, 95% CI=-5.85, -1.78) and cross-sectional deficits at age 15 across multiple domains relative to the PBC group (Cohen's d range, 0.31-0.48). They also performed worse than the FHR-BP group in verbal working memory at age 15 (d=0.42). Offspring at FHR-BP showed normative development compared with the PBC group, despite a cross-sectional deficit in semantic verbal fluency at age 15 (d=0.36). Offspring at FHR-SZ showed aberrant neurocognitive developmental alterations, whereas those at FHR-BP largely followed normal trajectories, with emerging deficits only in semantic verbal fluency. Examination of distinct neurocognitive trajectories as potential predictors of conversion to schizophrenia or bipolar disorder is warranted.