Connectome-Based Patterns of First-Episode Medication-Naïve Patients With Schizophrenia

Long-Biao Cui, Yongbin Wei, Yi-Bin Xi, Alessandra Griffa, Siemon C De Lange, René S Kahn, Hong Yin, Martijn P Van den Heuvel

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Emerging evidence indicates that a disruption in brain network organization may play an important role in the pathophysiology of schizophrenia. The neuroimaging fingerprint reflecting the pathophysiology of first-episode schizophrenia remains to be identified. Here, we aimed at characterizing the connectome organization of first-episode medication-naïve patients with schizophrenia. A cross-sectional structural and functional neuroimaging study using two independent samples (principal dataset including 42 medication-naïve, previously untreated patients and 48 healthy controls; replication dataset including 39 first-episode patients [10 untreated patients] and 66 healthy controls) was performed. Brain network architecture was assessed by means of white matter fiber integrity measures derived from diffusion-weighted imaging (DWI) and by means of structural-functional (SC-FC) coupling measured by combining DWI and resting-state functional magnetic resonance imaging. Connectome rich club organization was found to be significantly disrupted in medication-naïve patients as compared with healthy controls (P = .012, uncorrected), with rich club connection strength (P = .032, uncorrected) and SC-FC coupling (P < .001, corrected for false discovery rate) decreased in patients. Similar results were found in the replication dataset. Our findings suggest that a disruption of rich club organization and functional dynamics may reflect an early feature of schizophrenia pathophysiology. These findings add to our understanding of the neuropathological mechanisms of schizophrenia and provide new insights into the early stages of the disorder.

Original languageEnglish
Pages (from-to)1291-1299
Number of pages9
JournalSchizophrenia Bulletin
Issue number6
Early online date30 Mar 2019
Publication statusPublished - Nov 2019

Bibliographical note

Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.


This work was supported by the National Natural Science Foundation of China (grants 81801675 to L.-B.C., 81571651 to H.Y.); the State Scholarship Fund, China Scholarship Council (grants 201506040039 to Y.W., 201603170143 to L.-B.C); the Netherlands Organization for Scientific Research (grants ALWOP.179 and VIDI-452-16-015 to M.P.vdH.); a fellowship of MQ (to M.P.vdH.); and the Swiss National Science Foundation (grant #P2ELP3_172087 to A.G.).

FundersFunder number
Netherlands Organization for Scientific ResearchALWOP.179, VIDI-452-16-015
State Scholarship Fund
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung2ELP3_172087
National Natural Science Foundation of China81801675, 81571651
China Scholarship Council201506040039, 201603170143


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