Developmental Influences on Symptom Expression in Antipsychotic-Naive First-Episode Psychosis

Abstract

IntroductionThe neurodevelopmental model of psychosis was established over 30 years ago; however, the developmental influence on psychotic symptom expression - how a persons age affects clinical presentation in first-episode psychosis - has not been thoroughly investigated. MethodUsing generalized additive modeling, which allows for linear and non-linear functional forms of age-related change, we leveraged symptom data from a large sample of antipsychotic-naive individuals experiencing a first episode of psychosis (N=340, 12-40 years, 1-12 visits), collected at the University of Pittsburgh from 1990-2017. We examined relationships between age and severity of perceptual and non-perceptual positive symptoms and negative symptoms. We also tested for age-associated effects on change in positive or negative symptom severity following baseline assessment, and explored the time-varying relationship between perceptual and non-perceptual positive symptoms across adolescent development. ResultsIn the cross-sectional and longitudinal data, perceptual positive symptoms significantly decreased with increasing age (F=7.0, p=0.0007; q=0.003) while non-perceptual positive symptoms increased with increasing age (F=4.1, p=0.01, q=0.02). These relationships remained significant when SES, IQ, and illness duration were included as covariates. There were no developmental effects on change in positive or negative symptom severity (all p>0.25). Finally, an association between severity of non-perceptual and perceptual symptoms developed with increasing age, with a significant association starting at age 18. ConclusionThese findings suggest that as cognitive maturation proceeds, perceptual symptoms attenuate while non-perceptual symptoms are enhanced, reflecting influences of developmental processes on psychosis expression. Findings underscore how pathological brain-behavior relationships vary as a function of development.