TY - JOUR
T1 - Altered Cortical Gyrification Is Associated with Cortical and White Matter Microstructure in Individuals with Early Psychosis
T2 - A Multimodal Neuroimaging Study
AU - Sasabayashi, Daiki
AU - Seitz-Holland, Johanna
AU - Rathi, Yogesh
AU - Kim, Nicholas
AU - Cho, Kang Ik K.
AU - Mohandass, Dheshan
AU - Billah, Tashrif
AU - Haidar, Anastasia
AU - Kotler, Elana
AU - Cetin-Karayumak, Suheyla
AU - Jacobs, Grace R.
AU - Berberich, Cornelius
AU - Lewandowski, Kathryn E.
AU - Mesholam-Gately, Raquelle I.
AU - Wojcik, Joanne
AU - Haaf, Moritz
AU - Koike, Shinsuke
AU - Hirano, Yoji
AU - Takahashi, Tsutomu
AU - Suzuki, Michio
AU - Pasternak, Ofer
AU - Keshavan, Matcheri S.
AU - Holt, Daphne
AU - Öngür, Dost
AU - Breier, Alan
AU - Coleman, Michael J.
AU - Bouix, Sylvain
AU - Shenton, Martha E.
AU - Kubicki, Marek
N1 - Publisher Copyright:
© The Author(s) 2025. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact [email protected]. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/pages/standard-publication-reuse-rights)
PY - 2026/9
Y1 - 2026/9
N2 - Background and Hypothesis: Deviated brain folding patterns in psychosis may reflect dysfunctional brain development, more specifically cortical growth and white matter myelination. However, mechanisms that underlie the cortical folding disturbances and their relationship to clinical phenotypes in psychosis remain unknown. Study Design: This cross-sectional multimodal neuroimaging study combines structural and diffusion magnetic resonance imaging (MRI) in 203 individuals with early psychosis and 73 healthy individuals. The primary goal is to use local gyrification index (LGI), which quantifies cortical folding, to assess possible cortical abnormalities in subjects with early psychosis. The secondary goal is to combine gyrification measures with advanced diffusion MRI indices, namely, heterogeneity of fractional anisotropy (FA), a proxy for cortical cytoarchitecture, and free-water corrected FA, the latter associated with the tissue-related white matter microstructure. Finally, the relationship between these imaging measures with psychiatric symptoms and cognitive abilities are examined. Study Results: Compared to healthy individuals, the early psychosis group exhibited a significant LGI reduction, potentially reflecting sulcal widening and shallowing in the left temporo-parietal region. Local gyrification index was significantly associated with heterogeneity of FA in the corresponding region. Lower LGI was also associated with reduced FA in the white matter tracts connecting this region to the frontal lobe. Finally, lower LGI at the temporo-parietal junction was associated with more severe negative symptoms. Conclusions: We present the first in vivo evidence that anomalies in cortical folding may be linked to alterations in both the underlying cortical cytoarchitecture and associated microstructure of ipsilateral long-range white matter connections in psychosis.
AB - Background and Hypothesis: Deviated brain folding patterns in psychosis may reflect dysfunctional brain development, more specifically cortical growth and white matter myelination. However, mechanisms that underlie the cortical folding disturbances and their relationship to clinical phenotypes in psychosis remain unknown. Study Design: This cross-sectional multimodal neuroimaging study combines structural and diffusion magnetic resonance imaging (MRI) in 203 individuals with early psychosis and 73 healthy individuals. The primary goal is to use local gyrification index (LGI), which quantifies cortical folding, to assess possible cortical abnormalities in subjects with early psychosis. The secondary goal is to combine gyrification measures with advanced diffusion MRI indices, namely, heterogeneity of fractional anisotropy (FA), a proxy for cortical cytoarchitecture, and free-water corrected FA, the latter associated with the tissue-related white matter microstructure. Finally, the relationship between these imaging measures with psychiatric symptoms and cognitive abilities are examined. Study Results: Compared to healthy individuals, the early psychosis group exhibited a significant LGI reduction, potentially reflecting sulcal widening and shallowing in the left temporo-parietal region. Local gyrification index was significantly associated with heterogeneity of FA in the corresponding region. Lower LGI was also associated with reduced FA in the white matter tracts connecting this region to the frontal lobe. Finally, lower LGI at the temporo-parietal junction was associated with more severe negative symptoms. Conclusions: We present the first in vivo evidence that anomalies in cortical folding may be linked to alterations in both the underlying cortical cytoarchitecture and associated microstructure of ipsilateral long-range white matter connections in psychosis.
KW - early psychosis
KW - fractional anisotropy
KW - heterogeneity of fractional anisotropy
KW - local gyrification index
KW - magnetic resonance imaging
KW - multimodal
KW - tissue-specific fractional anisotropy
UR - https://www.scopus.com/pages/publications/105052820244
U2 - 10.1093/schbul/sbaf172
DO - 10.1093/schbul/sbaf172
M3 - Journal Article
C2 - 41104693
AN - SCOPUS:105052820244
SN - 0586-7614
VL - 52
JO - Schizophrenia Bulletin
JF - Schizophrenia Bulletin
IS - 5
M1 - sbaf172
ER -