PMID- 38243809
OWN - NLM
STAT- MEDLINE
DCOM- 20240430
LR  - 20240502
IS  - 1745-1701 (Electronic)
IS  - 0586-7614 (Print)
IS  - 0586-7614 (Linking)
VI  - 50
IP  - 3
DP  - 2024 Apr 30
TI  - Proteomic Biomarkers for the Prediction of Transition to Psychosis in Individuals 
      at Clinical High Risk: A Multi-cohort Model Development Study.
PG  - 579-588
LID - 10.1093/schbul/sbad184 [doi]
AB  - Psychosis risk prediction is one of the leading challenges in psychiatry. 
      Previous investigations have suggested that plasma proteomic data may be useful 
      in accurately predicting transition to psychosis in individuals at clinical high 
      risk (CHR). We hypothesized that an a priori-specified proteomic prediction model 
      would have strong predictive accuracy for psychosis risk and aimed to replicate 
      longitudinal associations between plasma proteins and transition to psychosis. 
      This study used plasma samples from participants in 3 CHR cohorts: the North 
      American Prodrome Longitudinal Studies 2 and 3, and the NEURAPRO randomized 
      control trial (total n = 754). Plasma proteomic data were quantified using mass 
      spectrometry. The primary outcome was transition to psychosis over the study 
      follow-up period. Logistic regression models were internally validated, and 
      optimism-corrected performance metrics derived with a bootstrap procedure. In the 
      overall sample of CHR participants (age: 18.5, SD: 3.9; 51.9% male), 20.4% 
      (n = 154) developed psychosis within 4.4 years. The a priori-specified model 
      showed poor risk-prediction accuracy for the development of psychosis 
      (C-statistic: 0.51 [95% CI: 0.50, 0.59], calibration slope: 0.45). At a group 
      level, Complement C8B, C4B, C5, and leucine-rich alpha-2 glycoprotein 1 (LRG1) were 
      associated with transition to psychosis but did not surpass correction for 
      multiple comparisons. This study did not confirm the findings from a previous 
      proteomic prediction model of transition from CHR to psychosis. Certain 
      complement proteins may be weakly associated with transition at a group level. 
      Previous findings, derived from small samples, should be interpreted with 
      caution.
CI  - (c) The Author(s) 2024. Published by Oxford University Press on behalf of the 
      Maryland Psychiatric Research Center.
FAU - Byrne, Jonah F
AU  - Byrne JF
AUID- ORCID: 0000-0002-7046-0630
AD  - Department of Psychiatry, Royal College of Surgeons in Ireland, University of 
      Medicine and Health Sciences, Dublin, Ireland.
AD  - SFI FutureNeuro Research Centre, Royal College of Surgeons in Ireland, University 
      of Medicine and Health Sciences, Dublin, Ireland.
FAU - Healy, Colm
AU  - Healy C
AUID- ORCID: 0000-0001-7974-1861
AD  - Department of Psychiatry, Royal College of Surgeons in Ireland, University of 
      Medicine and Health Sciences, Dublin, Ireland.
AD  - Department of Psychology, Royal College of Surgeons in Ireland, Dublin 2, 
      Ireland.
FAU - Focking, Melanie
AU  - Focking M
AD  - Department of Psychiatry, Royal College of Surgeons in Ireland, University of 
      Medicine and Health Sciences, Dublin, Ireland.
FAU - Susai, Subash Raj
AU  - Susai SR
AD  - Department of Psychiatry, Royal College of Surgeons in Ireland, University of 
      Medicine and Health Sciences, Dublin, Ireland.
FAU - Mongan, David
AU  - Mongan D
AUID- ORCID: 0000-0001-7931-9636
AD  - Department of Psychiatry, Royal College of Surgeons in Ireland, University of 
      Medicine and Health Sciences, Dublin, Ireland.
AD  - Centre for Public Health, Queen's University Belfast, Belfast, UK.
FAU - Wynne, Kieran
AU  - Wynne K
AD  - School of Biomolecular and Biomedical Science, Conway Institute, University 
      College Dublin, Dublin, Ireland.
FAU - Kodosaki, Eleftheria
AU  - Kodosaki E
AD  - School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Wales, UK.
FAU - Heurich, Meike
AU  - Heurich M
AD  - School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Wales, UK.
FAU - de Haan, Lieuwe
AU  - de Haan L
AD  - Department of Psychiatry, Academic Medical Center, Amsterdam, The Netherlands.
FAU - Hickie, Ian B
AU  - Hickie IB
AD  - Brain and Mind Centre, The University of Sydney, Sydney, NSW, Australia.
FAU - Smesny, Stefan
AU  - Smesny S
AD  - Department of Psychiatry, Jena University Hospital, Jena, Germany.
FAU - Thompson, Andrew
AU  - Thompson A
AD  - Centre for Youth Mental Health, University of Melbourne, Parkville, VIC, 
      Australia.
AD  - Orygen, The National Centre of Excellence in Youth Mental Health, Melbourne, VIC, 
      Australia.
FAU - Markulev, Connie
AU  - Markulev C
AD  - Centre for Youth Mental Health, University of Melbourne, Parkville, VIC, 
      Australia.
AD  - Orygen, The National Centre of Excellence in Youth Mental Health, Melbourne, VIC, 
      Australia.
FAU - Young, Alison Ruth
AU  - Young AR
AD  - Centre for Youth Mental Health, University of Melbourne, Parkville, VIC, 
      Australia.
AD  - Institute for Mental and Physical Health and Clinical Translation (IMPACT), 
      Deakin University, Geelong, VIC, Australia.
AD  - School of Health Sciences, University of Manchester, Manchester, UK.
FAU - Schafer, Miriam R
AU  - Schafer MR
AD  - Centre for Youth Mental Health, University of Melbourne, Parkville, VIC, 
      Australia.
AD  - Orygen, The National Centre of Excellence in Youth Mental Health, Melbourne, VIC, 
      Australia.
FAU - Riecher-Rossler, Anita
AU  - Riecher-Rossler A
AUID- ORCID: 0000-0001-6361-8789
AD  - Medical Faculty, University of Basel, Switzerland.
FAU - Mossaheb, Nilufar
AU  - Mossaheb N
AD  - Department of Psychiatry and Psychotherapy, Clinical Division of Social 
      Psychiatry, Medical University of Vienna, Vienna, Austria.
FAU - Berger, Gregor
AU  - Berger G
AD  - Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric 
      Hospital, University of Zurich, Zurich, Switzerland.
FAU - Schlogelhofer, Monika
AU  - Schlogelhofer M
AD  - BioPsyC-Biopsychosocial Corporation, Non-profit Association for Research Funding 
      Ltd, Vienna, Austria.
FAU - Nordentoft, Merete
AU  - Nordentoft M
AD  - Mental Health Center Copenhagen, Research Unit (CORE), Copenhagen, Denmark.
AD  - Department of Clinical Medicine, Faculty of Health and Medical Sciences, 
      University of Copenhagen, Copenhagen, Denmark.
FAU - Chen, Eric Y H
AU  - Chen EYH
AD  - Department of Psychiatry, School of Clinical Medicine, LKS Faculty of Medicine, 
      The University of Hong Kong, 2/F New Clinical Building, Queen Mary Hospital, Pok 
      Fu Lam, Hong Kong.
AD  - The State Key Laboratory of Brain and Cognitive Sciences, The University of Hong 
      Kong, Pok Fu Lam, Hong Kong.
FAU - Verma, Swapna
AU  - Verma S
AD  - Office of Education, Duke-NUS Graduate Medical School, Singapore, Singapore.
AD  - Department of Psychosis & East Region, Institute of Mental Health, Singapore, 
      Singapore.
FAU - Nieman, Dorien H
AU  - Nieman DH
AD  - Department of Psychiatry, Academic Medical Center, Amsterdam, The Netherlands.
FAU - Woods, Scott W
AU  - Woods SW
AD  - Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
FAU - Cornblatt, Barbara A
AU  - Cornblatt BA
AD  - Department of Psychiatry, Zucker Hillside Hospital, Long Island, NY, USA.
FAU - Stone, William S
AU  - Stone WS
AUID- ORCID: 0000-0003-2932-7288
AD  - Department of Psychiatry, Harvard Medical School at Beth Israel Deaconess Medical 
      Center and Massachusetts General Hospital, Boston, MA, USA.
FAU - Mathalon, Daniel H
AU  - Mathalon DH
AD  - Department of Psychiatry and Behavioral Sciences, University of California, San 
      Francisco, San Francisco, CA, USA.
AD  - Mental Health Service 116d, Veterans Affairs San Francisco Health Care System, 
      San Francisco, CA, USA.
FAU - Bearden, Carrie E
AU  - Bearden CE
AUID- ORCID: 0000-0002-8516-923X
AD  - Semel Institute for Neuroscience and Human Behavior, Departments of Psychiatry 
      and Biobehavioral Sciences and Psychology, University of California, Los Angeles, 
      CA, USA.
FAU - Cadenhead, Kristin S
AU  - Cadenhead KS
AD  - Department of Psychiatry, University of California, San Diego, CA, USA.
FAU - Addington, Jean
AU  - Addington J
AD  - Department of Psychiatry, Hotchkiss Brain Institute, University of Calgary, 
      Calgary, Canada.
FAU - Walker, Elaine F
AU  - Walker EF
AUID- ORCID: 0000-0002-9798-8101
AD  - Department of Psychology, Emory University, Atlanta, GA, USA.
AD  - Department of Psychiatry, Emory University, Atlanta, GA, USA.
FAU - Cannon, Tyrone D
AU  - Cannon TD
AD  - Department of Psychology, Yale University, New Haven, CT, USA.
AD  - Department of Psychiatry, Yale University, New Haven, CT, USA.
FAU - Cannon, Mary
AU  - Cannon M
AD  - Department of Psychiatry, Royal College of Surgeons in Ireland, University of 
      Medicine and Health Sciences, Dublin, Ireland.
AD  - SFI FutureNeuro Research Centre, Royal College of Surgeons in Ireland, University 
      of Medicine and Health Sciences, Dublin, Ireland.
AD  - Department of Psychiatry, Beaumont Hospital, Dublin 9, Ireland.
FAU - McGorry, Pat
AU  - McGorry P
AD  - Centre for Youth Mental Health, University of Melbourne, Parkville, VIC, 
      Australia.
AD  - Orygen, The National Centre of Excellence in Youth Mental Health, Melbourne, VIC, 
      Australia.
FAU - Amminger, Paul
AU  - Amminger P
AD  - Centre for Youth Mental Health, University of Melbourne, Parkville, VIC, 
      Australia.
AD  - Orygen, The National Centre of Excellence in Youth Mental Health, Melbourne, VIC, 
      Australia.
FAU - Cagney, Gerard
AU  - Cagney G
AUID- ORCID: 0000-0001-7189-9496
AD  - School of Biomolecular and Biomedical Science, Conway Institute, University 
      College Dublin, Dublin, Ireland.
FAU - Nelson, Barnaby
AU  - Nelson B
AD  - Centre for Youth Mental Health, University of Melbourne, Parkville, VIC, 
      Australia.
AD  - Orygen, The National Centre of Excellence in Youth Mental Health, Melbourne, VIC, 
      Australia.
FAU - Jeffries, Clark
AU  - Jeffries C
AD  - Renaissance Computing Institute, University of North Carolina, Chapel Hill, NC, 
      USA.
FAU - Perkins, Diana
AU  - Perkins D
AD  - Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA.
FAU - Cotter, David R
AU  - Cotter DR
AD  - Department of Psychiatry, Royal College of Surgeons in Ireland, University of 
      Medicine and Health Sciences, Dublin, Ireland.
AD  - SFI FutureNeuro Research Centre, Royal College of Surgeons in Ireland, University 
      of Medicine and Health Sciences, Dublin, Ireland.
AD  - Department of Psychiatry, Beaumont Hospital, Dublin 9, Ireland.
LA  - eng
GR  - 07TGF-1102/MH/NIMH NIH HHS/United States
GR  - 16/RC/3948/SFI_/Science Foundation Ireland/Ireland
GR  - 07TGF-1102/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Schizophr Bull
JT  - Schizophrenia bulletin
JID - 0236760
RN  - 0 (Biomarkers)
SB  - IM
MH  - Humans
MH  - *Psychotic Disorders/blood
MH  - Female
MH  - Male
MH  - *Biomarkers/blood
MH  - *Proteomics
MH  - Young Adult
MH  - Adolescent
MH  - *Prodromal Symptoms
MH  - Adult
MH  - Disease Progression
MH  - Longitudinal Studies
MH  - Risk
PMC - PMC11059811
OTO - NOTNLM
OT  - coagulation
OT  - complement
OT  - high risk
OT  - immune
OT  - model
OT  - prediction
OT  - proteome
OT  - psychosis
EDAT- 2024/01/20 21:41
MHDA- 2024/04/30 13:42
PMCR- 2024/01/19
CRDT- 2024/01/20 09:05
PHST- 2024/04/30 13:42 [medline]
PHST- 2024/01/20 21:41 [pubmed]
PHST- 2024/01/20 09:05 [entrez]
PHST- 2024/01/19 00:00 [pmc-release]
AID - 7578384 [pii]
AID - sbad184 [pii]
AID - 10.1093/schbul/sbad184 [doi]
PST - ppublish
SO  - Schizophr Bull. 2024 Apr 30;50(3):579-588. doi: 10.1093/schbul/sbad184.