Dissimilarity in Sulcal Width Patterns in the Cortex can be Used to Identify Patients with Schizophrenia with Extreme Deficits in Cognitive Performance

Joost Janssen*, Covadonga M. Diáz-Caneja, Clara Alloza, Anouck Schippers, Luciá De Hoyos, Javier Santonja, Pedro M. Gordaliza, Elizabeth E.L. Buimer, Neeltje E.M. Van Haren, Wiepke Cahn, Celso Arango, René S. Kahn, Hilleke E. Hulshoff Pol, Hugo G. Schnack

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

11 Citations (Scopus)


Schizophrenia is a biologically complex disorder with multiple regional deficits in cortical brain morphology. In addition, interindividual heterogeneity of cortical morphological metrics is larger in patients with schizophrenia when compared to healthy controls. Exploiting interindividual differences in the severity of cortical morphological deficits in patients instead of focusing on group averages may aid in detecting biologically informed homogeneous subgroups. The person-based similarity index (PBSI) of brain morphology indexes an individual's morphometric similarity across numerous cortical regions amongst a sample of healthy subjects. We extended the PBSI such that it indexes the morphometric similarity of an independent individual (eg, a patient) with respect to healthy control subjects. By employing a normative modeling approach on longitudinal data, we determined an individual's degree of morphometric dissimilarity to the norm. We calculated the PBSI for sulcal width (PBSI-SW) in patients with schizophrenia and healthy control subjects (164 patients and 164 healthy controls; 656 magnetic resonance imaging scans) and associated it with cognitive performance and cortical sulcation index. A subgroup of patients with markedly deviant PBSI-SW showed extreme deficits in cognitive performance and cortical sulcation. Progressive reduction of PBSI-SW in the schizophrenia group relative to healthy controls was driven by these deviating individuals. By explicitly leveraging interindividual differences in the severity of PBSI-SW deficits, neuroimaging-driven subgrouping of patients is feasible. As such, our results pave the way for future applications of morphometric similarity indices for subtyping of clinical populations.

Original languageEnglish
Pages (from-to)552-561
Number of pages10
JournalSchizophrenia Bulletin
Issue number2
Publication statusPublished - 1 Mar 2021

Bibliographical note

Publisher Copyright: © 2020 The Author(s) 2020. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.All rights reserved.


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