Individual deviations from normative models of brain structure in a large cross-sectional schizophrenia cohort.

Details

Serval ID
serval:BIB_D59637FBB425
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Individual deviations from normative models of brain structure in a large cross-sectional schizophrenia cohort.
Journal
Molecular psychiatry
Author(s)
Lv J., Di Biase M., Cash RFH, Cocchi L., Cropley V.L., Klauser P., Tian Y., Bayer J., Schmaal L., Cetin-Karayumak S., Rathi Y., Pasternak O., Bousman C., Pantelis C., Calamante F., Zalesky A.
ISSN
1476-5578 (Electronic)
ISSN-L
1359-4184
Publication state
Published
Issued date
07/2021
Peer-reviewed
Oui
Volume
26
Number
7
Pages
3512-3523
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
The heterogeneity of schizophrenia has defied efforts to derive reproducible and definitive anatomical maps of structural brain changes associated with the disorder. We aimed to map deviations from normative ranges of brain structure for individual patients and evaluate whether the loci of individual deviations recapitulated group-average brain maps of schizophrenia pathology. For each of 48 white matter tracts and 68 cortical regions, normative percentiles of variation in fractional anisotropy (FA) and cortical thickness (CT) were established using diffusion-weighted and structural MRI from healthy adults (n = 195). Individuals with schizophrenia (n = 322) were classified as either within the normative range for healthy individuals of the same age and sex (5-95% percentiles), infra-normal (<5% percentile) or supra-normal (>95% percentile). Repeating this classification for each tract and region yielded a deviation map for each individual. Compared to the healthy comparison group, the schizophrenia group showed widespread reductions in FA and CT, involving virtually all white matter tracts and cortical regions. Paradoxically, however, no more than 15-20% of patients deviated from the normative range for any single tract or region. Furthermore, 79% of patients showed infra-normal deviations for at least one locus (healthy individuals: 59 ± 2%, p < 0.001). Thus, while infra-normal deviations were common among patients, their anatomical loci were highly inconsistent between individuals. Higher polygenic risk for schizophrenia associated with a greater number of regions with infra-normal deviations in CT (r = -0.17, p = 0.006). We conclude that anatomical loci of schizophrenia-related changes are highly heterogeneous across individuals to the extent that group-consensus pathological maps are not representative of most individual patients. Normative modeling can aid in parsing schizophrenia heterogeneity and guiding personalized interventions.
Keywords
Adult, Anisotropy, Brain/diagnostic imaging, Cross-Sectional Studies, Humans, Schizophrenia/diagnostic imaging, Schizophrenia/genetics, White Matter/diagnostic imaging
Pubmed
Web of science
Create date
26/09/2020 16:16
Last modification date
02/02/2022 7:37
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