PMID- 33157263
OWN - NLM
STAT- MEDLINE
DCOM- 20210301
LR  - 20210920
IS  - 1095-9572 (Electronic)
IS  - 1053-8119 (Print)
IS  - 1053-8119 (Linking)
VI  - 226
DP  - 2021 Feb 1
TI  - Identifying neural signatures mediating behavioral symptoms and psychosis onset: 
      High-dimensional whole brain functional mediation analysis.
PG  - 117508
LID - S1053-8119(20)30993-9 [pii]
LID - 10.1016/j.neuroimage.2020.117508 [doi]
LID - 117508
AB  - Along the pathway from behavioral symptoms to the development of psychotic 
      disorders sits the multivariate mediating brain. The functional organization and 
      structural topography of large-scale multivariate neural mediators among patients 
      with brain disorders, however, are not well understood. Here, we design a 
      high-dimensional brain-wide functional mediation framework to investigate brain 
      regions that intermediate between baseline behavioral symptoms and future 
      conversion to full psychosis among individuals at clinical high risk (CHR). Using 
      resting-state functional magnetic resonance imaging (fMRI) data from 263 CHR 
      subjects, we extract an alpha brain atlas and a beta brain atlas: the former underlines 
      brain areas associated with prodromal symptoms and the latter highlights brain 
      areas associated with disease onset. In parallel, we identify and separate 
      mediators that potentially positively and negatively mediate symptoms and 
      psychosis, respectively, and quantify the effect of each neural mediator on 
      disease development. Taken together, these results paint a brain-wide picture of 
      neural markers that are potentially mediating behavioral symptoms and the 
      development of psychotic disorders; additionally, they underscore a statistical 
      framework that is useful to uncover large-scale intermediating variables in a 
      regulatory biological system.
CI  - Copyright (c) 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Chen, Oliver Y
AU  - Chen OY
AD  - Department of Engineering Science, University of Oxford, Oxford OX1 4AR, United 
      Kingdom. Electronic address: yibing.chen@seh.ox.ac.uk.
FAU - Cao, Hengyi
AU  - Cao H
AD  - Department of Psychology, Yale University, New Haven 06510, CT, United States; 
      Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, 
      Hempstead 11030, NY, United States; Division of Psychiatry Research, Zucker 
      Hillside Hospital, Glen Oaks 11004, NY, United States.
FAU - Phan, Huy
AU  - Phan H
AD  - School of Electronic Engineering and Computer Science, Queen Mary University of 
      London, London E1 4NS, United Kingdom.
FAU - Nagels, Guy
AU  - Nagels G
AD  - Department of Neurology, Universitair Ziekenhuis Brussel, 1090 Jette, Belgium.
FAU - Reinen, Jenna M
AU  - Reinen JM
AD  - IBM Watson Research Center, Yorktown Heights, NY 10598, United States.
FAU - Gou, Jiangtao
AU  - Gou J
AD  - Department of Mathematics and Statistics, Villanova University, PA 19085, United 
      States.
FAU - Qian, Tianchen
AU  - Qian T
AD  - Department of Statistics, Harvard University, Cambridge 02138, MA, United States; 
      Department of Statistics, University of California Irvine, Irvine 92697, CA, 
      United States.
FAU - Di, Junrui
AU  - Di J
AD  - Department of Biostatistics, Johns Hopkins University, Baltimore 21205, MD, 
      United States.
FAU - Prince, John
AU  - Prince J
AD  - Department of Engineering Science, University of Oxford, Oxford OX1 4AR, United 
      Kingdom.
FAU - Cannon, Tyrone D
AU  - Cannon TD
AD  - Department of Psychology, Yale University, New Haven 06510, CT, United States; 
      Department of Psychiatry, Yale University, New Haven 06510, CT, United States.
FAU - de Vos, Maarten
AU  - de Vos M
AD  - Faculty of Engineering Science, KU Leuven, Leuven 3001, Belgium; Faculty of 
      Medicine, KU Leuven, Leuven 3001, Belgium; KU Leuven Institute for Artificial 
      Intelligence, Leuven B-3000, Belgium.
LA  - eng
GR  - WT_/Wellcome Trust/United Kingdom
GR  - U01 MH081902/MH/NIMH NIH HHS/United States
GR  - UL1 TR001863/TR/NCATS NIH HHS/United States
GR  - 098461/Z/12/Z/WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20201104
PL  - United States
TA  - Neuroimage
JT  - NeuroImage
JID - 9215515
SB  - IM
MH  - Behavioral Symptoms/*diagnostic imaging/physiopathology
MH  - Brain/*diagnostic imaging/*physiopathology
MH  - Brain Mapping/methods
MH  - Female
MH  - Humans
MH  - Image Interpretation, Computer-Assisted/methods
MH  - Magnetic Resonance Imaging/methods
MH  - Male
MH  - Mediation Analysis
MH  - *Prodromal Symptoms
MH  - Psychotic Disorders/*diagnostic imaging/physiopathology
MH  - Young Adult
PMC - PMC7836235
COIS- Declaration of Competing Interest The authors declare no competing interests.
EDAT- 2020/11/07 06:00
MHDA- 2021/03/02 06:00
PMCR- 2021/02/01
CRDT- 2020/11/06 20:11
PHST- 2020/08/14 00:00 [received]
PHST- 2020/10/19 00:00 [revised]
PHST- 2020/10/22 00:00 [accepted]
PHST- 2020/11/07 06:00 [pubmed]
PHST- 2021/03/02 06:00 [medline]
PHST- 2020/11/06 20:11 [entrez]
PHST- 2021/02/01 00:00 [pmc-release]
AID - S1053-8119(20)30993-9 [pii]
AID - 117508 [pii]
AID - 10.1016/j.neuroimage.2020.117508 [doi]
PST - ppublish
SO  - Neuroimage. 2021 Feb 1;226:117508. doi: 10.1016/j.neuroimage.2020.117508. Epub 
      2020 Nov 4.