Developmental influences on symptom expression in antipsychotic-naïve first-episode psychosis

Abstract

Background The neurodevelopmental model of psychosis was established over 30 years ago; however, the developmental influence on psychotic symptom expression – how age affects clinical presentation in first-episode psychosis – has not been thoroughly investigated. Methods Using 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-naïve individuals with first-episode psychosis (N = 340, 12–40 years, 1–12 visits), collected at the University of Pittsburgh from 1990 to 2017. We examined relationships between age and severity of perceptual and non-perceptual positive symptoms and negative symptoms. We 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. Results Perceptual positive symptom severity significantly decreased with increasing age (F = 7.0, p = 0.0007; q = 0.003) while non-perceptual positive symptom severity increased with age (F = 4.1, p = 0.01, q = 0.02). Anhedonia severity increased with increasing age (F = 6.7, p = 0.00035; q = 0.0003), while flat affect decreased in severity with increased age (F = 9.8, p = 0.002; q = 0.006). Findings remained significant when parental 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). Beginning at age 18, there was a statistically significant association between severity of non-perceptual and perceptual symptoms. This relationship increased in strength throughout adulthood. Conclusions These findings suggest that as maturation proceeds, perceptual symptoms attenuate while non-perceptual symptoms are enhanced. Findings underscore how pathological brain–behavior relationships vary as a function of development.

Thinner cortex is associated with psychosis onset in individuals at Clinical High Risk for Developing Psychosis: An ENIGMA Working Group mega-analysis

“…Several brain regions implicated in psychosis show protracted developmental courses continuing through adolescence [53][54][55][56][57][58][59][60][61][62][63] , suggesting that morphometric alterations associated with psychosis risk vary with age. Indeed, there are developmental influences on psychotic symptom presentation [64][65][66][67][68] , perhaps driven by differences in regional brain changes. It is not fully understood how age-related patterns in brain morphometry in CHR differ from normal development.…”

Age-associated alterations in thalamocortical structural connectivity in youths with a psychosis-spectrum disorder

“…To determine time periods in which significant change was occurring in each group, we used the R package gratia 130 to estimate a multivariate normal distribution whose vector of means and covariance were defined by the fitted GAM parameters to simulate 10,000 GAM fits and their first derivatives, generated at 0.1-year age intervals. Similar to previous publications 57 , 61 , 131 and in line with recent guidelines 132 , we defined significant intervals of age-related change in MRI measures as ages when the 95% confidence intervals of simulated GAM fits did not include zero.…”

Age-associated alterations in thalamocortical structural connectivity in psychosis-spectrum youths

“…To determine time periods in which significant change was occurring in each group, we used a multivariate normal distribution whose vector of means and covariance were defined by the fitted GAM parameters to simulate 10,000 GAM fits and their first derivatives, generated at 0.1-year age intervals. Similar to previous publications [85][86][87] and in line with recent guidelines, 88 we defined significant intervals of age-related change in MRI measures as ages when the 95% confidence intervals of simulated GAM fits did not include zero.…”