Brain gray matter network organization in psychotic disorders

Wenjing Zhang, Du Lei, Sarah K. Keedy, Elena I. Ivleva, Seenae Eum, Li Yao, Carol A. Tamminga, Brett A. Clementz, Matcheri S. Keshavan, Godfrey D. Pearlson, Elliot S. Gershon, Jeffrey R. Bishop, Qiyong Gong, Su Lui, John A. Sweeney

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Abnormal neuroanatomic brain networks have been reported in schizophrenia, but their characterization across patients with psychotic disorders, and their potential alterations in nonpsychotic relatives, remain to be clarified. Participants recruited by the Bipolar and Schizophrenia Network for Intermediate Phenotypes consortium included 326 probands with psychotic disorders (107 with schizophrenia (SZ), 87 with schizoaffective disorder (SAD), 132 with psychotic bipolar disorder (BD)), 315 of their nonpsychotic first-degree relatives and 202 healthy controls. Single-subject gray matter graphs were extracted from structural MRI scans, and whole-brain neuroanatomic organization was compared across the participant groups. Compared with healthy controls, psychotic probands showed decreased nodal efficiency mainly in bilateral superior temporal regions. These regions had altered morphological relationships primarily with frontal lobe regions, and their network-level alterations were associated with positive symptoms of psychosis. Nonpsychotic relatives showed lower nodal centrality metrics in the prefrontal cortex and subcortical regions, and higher nodal centrality metrics in the left cingulate cortex and left thalamus. Diagnosis-specific analysis indicated that individuals with SZ had lower nodal efficiency in bilateral superior temporal regions than controls, probands with SAD only exhibited lower nodal efficiency in the left superior and middle temporal gyrus, and individuals with psychotic BD did not show significant differences from healthy controls. Our findings provide novel evidence of clinically relevant disruptions in the anatomic association of the superior temporal lobe with other regions of whole-brain networks in patients with psychotic disorders, but not in their unaffected relatives, suggesting that it is a disease-related trait. Network disorganization primarily involving frontal lobe and subcortical regions in nonpsychotic relatives may be related to familial illness risk.

Original languageEnglish (US)
Pages (from-to)666-674
Number of pages9
Issue number4
StatePublished - Mar 1 2020

Bibliographical note

Funding Information:
This work was supported by the National Institute of Mental Health Grant Nos. MH077851 (to CAT), MH078113 (to MSK), MH077945 (to GDP), MH077852 (to Gunvant K. Thaker), and MH077862 (to JAS). The National Institute of Mental Health had no further role in study design; in the collection, analysis, and interpretation of the data; in the writing of the report; and in the decision to submit the paper for publication. The work was also supported by the National Natural Science Foundation of China (81671664, 81820108018, and 81621003), Miaozi Project in Science and Technology Innovation Program of Sichuan Province and 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University (Project No. ZYYC08001, ZYJC18020). CAT has served on the advisory board for drug development for Intra-Cellular Therapies, Inc., as an ad hoc consultant for Eli Lilly, Sunovion, Astellas, Pfizer, and Merck, has been a council member and unpaid volunteer for the National Alliance on Mental Illness, and served as deputy editor for the American Psychiatric Association. MSK has received research support from Sunovion and GlaxoSmithKline. Remaining authors report no competing interests.

Publisher Copyright:
© 2019, The Author(s).


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