Dataset Information

In vivo white matter microstructure in adolescents with early-onset psychosis: a multi-site mega-analysis.

ABSTRACT: Emerging evidence suggests brain white matter alterations in adolescents with early-onset psychosis (EOP; age of onset <18 years). However, as neuroimaging methods vary and sample sizes are modest, results remain inconclusive. Using harmonized data processing protocols and a mega-analytic approach, we compared white matter microstructure in EOP and healthy controls using diffusion tensor imaging (DTI). Our sample included 321 adolescents with EOP (median age = 16.6 years, interquartile range (IQR) = 2.14, 46.4% females) and 265 adolescent healthy controls (median age = 16.2 years, IQR = 2.43, 57.7% females) pooled from nine sites. All sites extracted mean fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) for 25 white matter regions of interest per participant. ComBat harmonization was performed for all DTI measures to adjust for scanner differences. Multiple linear regression models were fitted to investigate case-control differences and associations with clinical variables in regional DTI measures. We found widespread lower FA in EOP compared to healthy controls, with the largest effect sizes in the superior longitudinal fasciculus (Cohen's d = 0.37), posterior corona radiata (d = 0.32), and superior fronto-occipital fasciculus (d = 0.31). We also found widespread higher RD and more localized higher MD and AD. We detected significant effects of diagnostic subgroup, sex, and duration of illness, but not medication status. Using the largest EOP DTI sample to date, our findings suggest a profile of widespread white matter microstructure alterations in adolescents with EOP, most prominently in male individuals with early-onset schizophrenia and individuals with a shorter duration of illness.

SUBMITTER: Barth C

PROVIDER: S-EPMC10005938 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Publications

In vivo white matter microstructure in adolescents with early-onset psychosis: a multi-site mega-analysis.

Barth Claudia C Kelly Sinead S Nerland Stener S Jahanshad Neda N Alloza Clara C Ambrogi Sonia S Andreassen Ole A OA Andreou Dimitrios D Arango Celso C Baeza Inmaculada I Banaj Nerisa N Bearden Carrie E CE Berk Michael M Bohman Hannes H Castro-Fornieles Josefina J Chye Yann Y Crespo-Facorro Benedicto B de la Serna Elena E Díaz-Caneja Covadonga M CM Gurholt Tiril P TP Hegarty Catherine E CE James Anthony A Janssen Joost J Johannessen Cecilie C Jönsson Erik G EG Karlsgodt Katherine H KH Kochunov Peter P Lois Noemi G NG Lundberg Mathias M Myhre Anne M AM Pascual-Diaz Saül S Piras Fabrizio F Smelror Runar E RE Spalletta Gianfranco G Stokkan Therese S TS Sugranyes Gisela G Suo Chao C Thomopoulos Sophia I SI Tordesillas-Gutiérrez Diana D Vecchio Daniela D Wedervang-Resell Kirsten K Wortinger Laura A LA Thompson Paul M PM Agartz Ingrid I

Molecular psychiatry 20221212 3

Emerging evidence suggests brain white matter alterations in adolescents with early-onset psychosis (EOP; age of onset <18 years). However, as neuroimaging methods vary and sample sizes are modest, results remain inconclusive. Using harmonized data processing protocols and a mega-analytic approach, we compared white matter microstructure in EOP and healthy controls using diffusion tensor imaging (DTI). Our sample included 321 adolescents with EOP (median age = 16.6 years, interquartile range (IQ ...[more]

PMID: 36510004

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Project description:White matter hyperintensities negatively impact white matter structure and relate to cognitive decline in aging. Diffusion tensor imaging detects changes to white matter microstructure, both within the white matter hyperintensity and extending into surrounding (perilesional) normal-appearing white matter. However, diffusion tensor imaging markers are not specific to tissue components, complicating the interpretation of previous microstructural findings. Myelin water imaging is a novel imaging technique that provides specific markers of myelin content (myelin water fraction) and interstitial fluid (geometric mean T2). Here we combined diffusion tensor imaging and myelin water imaging to examine tissue characteristics in white matter hyperintensities and perilesional white matter in 80 individuals (47 older adults and 33 individuals with chronic stroke). To measure perilesional normal-appearing white matter, white matter hyperintensity masks were dilated in 2 mm segments up to 10 mm in distance from the white matter hyperintensity. Fractional anisotropy, mean diffusivity, myelin water fraction, and geometric mean T2 were extracted from white matter hyperintensities and perilesional white matter. We observed a spatial gradient of higher mean diffusivity and geometric mean T2, and lower fractional anisotropy, in the white matter hyperintensity and perilesional white matter. In the chronic stroke group, myelin water fraction was reduced in the white matter hyperintensity but did not show a spatial gradient in perilesional white matter. Across the entire sample, white matter metrics within the white matter hyperintensity related to whole-brain white matter hyperintensity volume; with increasing white matter hyperintensity volume there was increased mean diffusivity and geometric mean T2, and decreased myelin water fraction in the white matter hyperintensity. Normal-appearing white matter adjacent to white matter hyperintensities exhibits characteristics of a transitional stage between healthy white matter and white matter hyperintensities. This effect was observed in markers sensitive to interstitial fluid, but not in myelin water fraction, the specific marker of myelin concentration. Within the white matter hyperintensity, interstitial fluid was higher and myelin concentration was lower in individuals with more severe cerebrovascular disease. Our data suggests white matter hyperintensities have penumbra-like effects in perilesional white matter that specifically reflect increased interstitial fluid, with no changes to myelin concentration. In contrast, within the white matter hyperintensity there are varying levels of demyelination, which vary based on the severity of cerebrovascular disease. Diffusion tensor imaging and myelin imaging may be useful clinical markers to predict white matter hyperintensity formation, and to stage neuronal damage within white matter hyperintensities.

Dataset Information

In vivo white matter microstructure in adolescents with early-onset psychosis: a multi-site mega-analysis.

Publications

In vivo white matter microstructure in adolescents with early-onset psychosis: a multi-site mega-analysis.

Similar Datasets

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