Duration of Untreated Psychosis Correlates With Brain Connectivity and Morphology in Medication-Naïve Patients With First-Episode Psychosis

Abstract

Background: In the United States, the average duration of untreated psychosis (DUP) is 21 months, and it remains unknown how longer DUP may affect brain functioning in antipsychotic-naïve patients with first-episode psychosis. The objective was to determine the effects of DUP on functional connectivity and brain morphology measured with resting-state functional and structural magnetic resonance imaging.

Methods: Medication-naïve patients with first-episode psychosis were referred from various clinical settings. After accounting for exclusion criteria, attrition, and data quality, final analyses included 55 patients (35 male and 20 female; mean age, 24.18 years). Patients with first-episode psychosis were subjected to a 16-week trial of risperidone, a commonly used antipsychotic drug. Treatment response was calculated as change in the psychosis subscale of the Brief Psychiatric Rating Scale between baseline and 16 weeks. Resting-state functional connectivity magnetic resonance imaging and brain morphology (surface area and cortical thickness) were assessed.

Results: Longer DUP was associated with worse treatment response and reduced functional connectivity-more specifically in the default, salience, and executive networks. Moreover, longer DUP was associated with reduced surface area in the salience and executive networks and with increased cortical thickness in the default mode and salience networks. When the functional connectivity of the default mode network was added as a mediator, the relationship between DUP and treatment response was no longer significant.

Conclusions: These data suggest that several neurobiological alterations in the form of reduced functional connectivity and surface area and increased cortical thickness underpin the effect of prolonged DUP.

Trial registration: ClinicalTrials.gov NCT03442101 NCT02034253.

Keywords: Brain networks; Duration of untreated psychosis; Functional connectivity; Morphology; Resting state; Treatment response.

Conflict of interest statement

Conflict of Interest: All authors report no relevant biomedical financial interests or potential conflicts of interest.

Copyright © 2019 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1.

Clusters of significant partial correlations between DUP with FC (pFDR < 0.05,) and masks rendered on the fsaverage brain used for brain morphology analyses and partial correlation plots for A) default mode, B) salience, and C) central executive network. For FC-DUP correlations, signal from all clusters were averaged and plotted with DUP for data visualization purposes. All data are standardized residuals from controlling for age, gender, and intracranial volume (morphological analyses).

Figure 2.

aDUP significantly predicts TR; bwhen FC DMN is added to the model, DUP no longer predicts TR (Sobel test [z = −1.94, p = 0.03]). DUP = duration of untreated psychosis; TR = treatment response; FC DMN = signal from significant clusters from Figure 1A.