PMID- 34024906
OWN - NLM
STAT- MEDLINE
DCOM- 20220314
LR  - 20240404
IS  - 1476-5578 (Electronic)
IS  - 1359-4184 (Print)
IS  - 1359-4184 (Linking)
VI  - 26
IP  - 11
DP  - 2021 Nov
TI  - White matter changes in psychosis risk relate to development and are not impacted 
      by the transition to psychosis.
PG  - 6833-6844
LID - 10.1038/s41380-021-01128-8 [doi]
AB  - 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.
CI  - (c) 2021. The Author(s), under exclusive licence to Springer Nature Limited.
FAU - Di Biase, Maria A
AU  - Di Biase MA
AUID- ORCID: 0000-0002-7100-651X
AD  - Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, 
      Boston, MA, USA. dibiasem@unimelb.edu.au.
AD  - Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of 
      Melbourne and Melbourne Health, Carlton South, VIC, Australia. 
      dibiasem@unimelb.edu.au.
FAU - Cetin-Karayumak, Suheyla
AU  - Cetin-Karayumak S
AUID- ORCID: 0000-0002-3315-5821
AD  - Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, 
      Boston, MA, USA.
AD  - Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 
      Boston, MA, USA.
FAU - Lyall, Amanda E
AU  - Lyall AE
AUID- ORCID: 0000-0001-8049-516X
AD  - Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, 
      Boston, MA, USA.
AD  - Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, 
      Boston, MA, USA.
FAU - Zalesky, Andrew
AU  - Zalesky A
AD  - Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of 
      Melbourne and Melbourne Health, Carlton South, VIC, Australia.
FAU - Cho, Kang Ik Kevin
AU  - Cho KIK
AD  - Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, 
      Boston, MA, USA.
FAU - Zhang, Fan
AU  - Zhang F
AUID- ORCID: 0000-0002-5032-6039
AD  - Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 
      Boston, MA, USA.
FAU - Kubicki, Marek
AU  - Kubicki M
AUID- ORCID: 0000-0002-3989-8212
AD  - Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, 
      Boston, MA, USA.
AD  - Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 
      Boston, MA, USA.
AD  - Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, 
      Boston, MA, USA.
FAU - Rathi, Yogesh
AU  - Rathi Y
AD  - Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, 
      Boston, MA, USA.
AD  - Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 
      Boston, MA, USA.
FAU - Lyons, Monica G
AU  - Lyons MG
AD  - Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, 
      Boston, MA, USA.
FAU - Bouix, Sylvain
AU  - Bouix S
AUID- ORCID: 0000-0003-1326-6054
AD  - Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, 
      Boston, MA, USA.
FAU - Billah, Tashrif
AU  - Billah T
AD  - Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, 
      Boston, MA, USA.
FAU - Anticevic, Alan
AU  - Anticevic A
AD  - Department of Psychiatry and Psychology, Yale University, New Haven, CT, USA.
FAU - Schleifer, Charlie
AU  - Schleifer C
AD  - UCLA School of Medicine, Los Angeles, CA, USA.
FAU - Adkinson, Brendan D
AU  - Adkinson BD
AD  - Yale Interdepartmental Neuroscience Program, Yale School of Medicine, New Haven, 
      CT, USA.
FAU - Ji, Jie Lisa
AU  - Ji JL
AUID- ORCID: 0000-0002-6280-9070
AD  - Department of Psychiatry and Psychology, Yale University, New Haven, CT, USA.
FAU - Tamayo, Zailyn
AU  - Tamayo Z
AD  - Department of Psychiatry and Psychology, Yale University, New Haven, CT, USA.
FAU - Addington, Jean
AU  - Addington J
AUID- ORCID: 0000-0002-8298-0756
AD  - Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
FAU - Bearden, Carrie E
AU  - Bearden CE
AUID- ORCID: 0000-0002-8516-923X
AD  - Department of Psychiatry and Biobehavioral Sciences, Semel Institute for 
      Neuroscience and Human Behavior and Department of Psychology, University of 
      California-Los Angeles, Los Angeles, CA, USA.
FAU - Cornblatt, Barbara A
AU  - Cornblatt BA
AD  - Department of Psychiatry and Psychology, The Feinstein Institute for Medical 
      Research, Manhasset, NY, USA.
AD  - Department of Psychology, Hofstra North Shore-LIJ School of Medicine, Hempstead, 
      NY, USA.
AD  - The Zucker Hillside Hospital, New York, NY, USA.
FAU - Keshavan, Matcheri S
AU  - Keshavan MS
AD  - Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA, USA.
FAU - Mathalon, Daniel H
AU  - Mathalon DH
AD  - University of California, San Francisco, San Francisco, CA, USA.
AD  - San Francisco VA Medical Center, San Francisco, CA, USA.
FAU - McGlashan, Thomas H
AU  - McGlashan TH
AD  - Department of Psychiatry and Psychology, Yale University, New Haven, CT, USA.
FAU - Perkins, Diana O
AU  - Perkins DO
AD  - Department of Psychology, Hofstra North Shore-LIJ School of Medicine, Hempstead, 
      NY, USA.
AD  - University of North Carolina (UNC), Chapel Hill, NC, USA.
FAU - Cadenhead, Kristen S
AU  - Cadenhead KS
AD  - Department of Psychiatry, University of California San Diego (UCSD), La Jolla, 
      CA, USA.
FAU - Tsuang, Ming T
AU  - Tsuang MT
AUID- ORCID: 0000-0002-0076-5340
AD  - Department of Psychiatry, University of California San Diego (UCSD), La Jolla, 
      CA, USA.
FAU - Woods, Scott W
AU  - Woods SW
AD  - Department of Psychiatry and Psychology, Yale University, New Haven, CT, USA.
FAU - Stone, William S
AU  - Stone WS
AD  - Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA, USA.
FAU - Shenton, Martha E
AU  - Shenton ME
AD  - Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, 
      Boston, MA, USA.
AD  - Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 
      Boston, MA, USA.
AD  - Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, 
      Boston, MA, USA.
FAU - Cannon, Tyrone D
AU  - Cannon TD
AD  - Department of Psychiatry and Psychology, Yale University, New Haven, CT, USA.
FAU - Pasternak, Ofer
AU  - Pasternak O
AUID- ORCID: 0000-0002-7078-6446
AD  - Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, 
      Boston, MA, USA.
AD  - Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 
      Boston, MA, USA.
LA  - eng
GR  - U01 MH081902/MH/NIMH NIH HHS/United States
GR  - U01 MH076989/MH/NIMH NIH HHS/United States
GR  - R01 MH074794/MH/NIMH NIH HHS/United States
GR  - P41 EB015902/EB/NIBIB NIH HHS/United States
GR  - U01 MH081928/MH/NIMH NIH HHS/United States
GR  - R01 MH102377/MH/NIMH NIH HHS/United States
GR  - U01 MH109977/MH/NIMH NIH HHS/United States
GR  - U01 MH082022/MH/NIMH NIH HHS/United States
GR  - U01 MH081984/MH/NIMH NIH HHS/United States
GR  - UL1 TR001863/TR/NCATS NIH HHS/United States
GR  - T32 GM136651/GM/NIGMS NIH HHS/United States
GR  - R01 MH108574/MH/NIMH NIH HHS/United States
GR  - K01 MH115247/MH/NIMH NIH HHS/United States
GR  - U01 MH081857/MH/NIMH NIH HHS/United States
GR  - U01 MH082004/MH/NIMH NIH HHS/United States
GR  - U01 MH081944/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20210524
PL  - England
TA  - Mol Psychiatry
JT  - Molecular psychiatry
JID - 9607835
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Child
MH  - Child, Preschool
MH  - Corpus Callosum/pathology
MH  - Humans
MH  - Longitudinal Studies
MH  - Prodromal Symptoms
MH  - *Psychotic Disorders/pathology
MH  - *White Matter/pathology
MH  - Young Adult
PMC - PMC8611104
MID - NIHMS1720538
COIS- Conflict of Interest Statement: The authors have nothing to disclose.
EDAT- 2021/05/25 06:00
MHDA- 2022/03/15 06:00
PMCR- 2022/11/01
CRDT- 2021/05/24 07:56
PHST- 2020/11/22 00:00 [received]
PHST- 2021/04/14 00:00 [accepted]
PHST- 2021/05/25 06:00 [pubmed]
PHST- 2022/03/15 06:00 [medline]
PHST- 2021/05/24 07:56 [entrez]
PHST- 2022/11/01 00:00 [pmc-release]
AID - 10.1038/s41380-021-01128-8 [pii]
AID - 10.1038/s41380-021-01128-8 [doi]
PST - ppublish
SO  - Mol Psychiatry. 2021 Nov;26(11):6833-6844. doi: 10.1038/s41380-021-01128-8. Epub 
      2021 May 24.