Open AccessWhite matter changes in psychosis risk relate to development and are not impacted by the transition to psychosis
Author(s) -
Maria A. Di Biase,
Suheyla Cetin-Karayumak,
Amanda E. Lyall,
Andrew Zalesky,
Kang Ik Kevin Cho,
Zhanming Fan,
Marek Kubicki,
Yogesh Rathi,
Marion Lyons,
Sylvain Bouix,
Tashrif Billah,
Alan Antičević,
Charles Schleifer,
Brendan Adkinson,
Jie Lisa Ji,
Zailyn Tamayo,
Jean Addington,
Carrie Bearden,
Barbara A. Cornblatt,
Matcheri S. Keshavan,
Daniel H. Mathalon,
Thomas H. McGlashan,
Diana O. Perkins,
Kristen Cadenhead,
Ming T. Tsuang,
Scott W. Woods,
William S. Stone,
Martha E. Shenton,
Tyrone D. Can,
Ofer Pasternak
Publication year - 2021
Publication title -
molecular psychiatry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.071
H-Index - 213
eISSN - 1476-5578
pISSN - 1359-4184
DOI - 10.1038/s41380-021-01128-8
Subject(s) - psychosis , white matter , prodrome , fractional anisotropy , psychology , medicine , cohort , young adult , prospective cohort study , magnetic resonance imaging , pediatrics , psychiatry , radiology
Subtle alterations in white matter microstructure are observed in youth at clinical high risk (CHR) for psychosis. However, the timing of these changes and their relationships to the emergence of psychosis remain unclear. Here, we track the evolution of white matter abnormalities in a large, longitudinal cohort of CHR individuals comprising the North American Prodrome Longitudinal Study (NAPLS-3). Multi-shell diffusion magnetic resonance imaging data were collected across multiple timepoints (1-5 over 1 year) in 286 subjects (aged 12-32 years): 25 CHR individuals who transitioned to psychosis (CHR-P; 61 scans), 205 CHR subjects with unknown transition outcome after the 1-year follow-up period (CHR-U; 596 scans), and 56 healthy controls (195 scans). Linear mixed effects models were fitted to infer the impact of age and illness-onset on variation in the fractional anisotropy of cellular tissue (FA T ) and the volume fraction of extracellular free water (FW). Baseline measures of white matter microstructure did not differentiate between HC, CHR-U and CHR-P individuals. However, age trajectories differed between the three groups in line with a developmental effect: CHR-P and CHR-U groups displayed higher FA T in adolescence, and 4% lower FA T by 30 years of age compared to controls. Furthermore, older CHR-P subjects (20+ years) displayed 4% higher FW in the forceps major (p < 0.05). Prospective analysis in CHR-P did not reveal a significant impact of illness onset on regional FA T or FW, suggesting that transition to psychosis is not marked by dramatic change in white matter microstructure. Instead, clinical high risk for psychosis-regardless of transition outcome-is characterized by subtle age-related white matter changes that occur in tandem with development.