Trajectories of Mismatch Negativity and P3a Amplitude Development From Ages 9 to 16 Years in Children With Risk Factors for Schizophrenia

Background: Mismatch negativity (MMN) and P3a amplitude reductions are robust abnormalities of sensory information processing in schizophrenia, but they are variably present in different profiles of risk (family history vs. clinical high risk) for the disorder. This study aimed to determine whether these abnormalities characterize children presenting replicated risk factors for schizophrenia, using longitudinal assessment over the ages of 9–16 years in children with multiple replicated antecedents of schizophrenia (ASz) and with family history of schizophrenia (FHx), relative to typically developing (TD) peers. Methods: A total of 105 children (52 female) sampled from the community were assessed at ages 9–12 years and approximately 2 and 4 years later. Linear mixed models were fitted to MMN and P3a peak amplitudes and latencies, with intercept and slope estimates from 32 ASz and 28 FHx children compared with those of 45 TD peers. Results: In ASz relative to TD children, MMN amplitude initially increased and then prominently decreased during adolescence. Both ASz and FHx children had greater P3a amplitude than TD children at 11 years, which decreased with age, in contrast to P3a amplitude increasing during adolescence in TD youths. MMN abnormalities were specific to ASz children who continued to present symptoms during follow-up. Conclusions: Age-dependent MMN and P3a abnormalities demarcate adolescent development of ASz and FHx from TD children, with auditory change detection abnormalities specific to ASz children with continuing symptoms and attention-orienting abnormalities characterizing both ASz and FHx risk profiles. Follow-up is required to determine whether these abnormalities index vulnerability for schizophrenia or an illness nonspecific developmental delay. Funding: QUT Project 2018001348 (ARC FT170100294)