Differential expression of haptoglobin in individuals at clinical high risk of psychosis and its association with global functioning and clinical symptoms.


Journal

Brain, behavior, and immunity
ISSN: 1090-2139
Titre abrégé: Brain Behav Immun
Pays: Netherlands
ID NLM: 8800478

Informations de publication

Date de publication:
12 Jan 2024
Historique:
received: 11 07 2023
revised: 07 11 2023
accepted: 18 12 2023
medline: 15 1 2024
pubmed: 15 1 2024
entrez: 14 1 2024
Statut: aheadofprint

Résumé

Immune dysregulation has been observed in patients with schizophrenia or first-episode psychosis, but few have examined dysregulation in those at clinical high-risk (CHR) for psychosis. The aim of this study was to examine whether the peripheral blood-based proteome was dysregulated in those with CHR. Secondly, we examined whether baseline dysregulation was related to current and future functioning and clinical symptoms. We used data from participants of the North American Prodromal Longitudinal Studies (NAPLS) 2 and 3 (n = 715) who provided blood samples (Unaffected Comparison Subjects (UC) n = 223 and CHR n = 483). Baseline proteomic data was quantified from plasma samples using mass spectrometry. Differential expression was examined between CHR and UC using logistic regression. Psychosocial functioning was measured using the Global Assessment of Functioning scale (GAF). Symptoms were measured using the subscale scores from the Scale of Psychosis-risk Symptoms; Positive, Negative, General, and Disorganised. Three measures of each outcome were included: Baseline, longest available follow-up (last follow-up) and most severe follow-up (MSF). Associations between the proteomic data, GAF and symptoms were assessed using ordinal regression. Of the 99 proteins quantified, six were differentially expressed between UC and CHR. However, only haptoglobin (HP) survived FDR-correction (OR:1.45, 95 %CI:1.23-1.69, p We demonstrate that elevated HP is robustly observed in those at CHR for psychosis, irrespective of transition to psychosis. HP is longitudinally associated with poorer functioning and greater symptom severity. These results agree with previous reports of increased HP gene expression in individuals at-risk for psychosis and with the dysfunction of the acute phase inflammatory response seen in psychotic disorders.

Sections du résumé

BACKGROUND BACKGROUND
Immune dysregulation has been observed in patients with schizophrenia or first-episode psychosis, but few have examined dysregulation in those at clinical high-risk (CHR) for psychosis. The aim of this study was to examine whether the peripheral blood-based proteome was dysregulated in those with CHR. Secondly, we examined whether baseline dysregulation was related to current and future functioning and clinical symptoms.
METHODS METHODS
We used data from participants of the North American Prodromal Longitudinal Studies (NAPLS) 2 and 3 (n = 715) who provided blood samples (Unaffected Comparison Subjects (UC) n = 223 and CHR n = 483). Baseline proteomic data was quantified from plasma samples using mass spectrometry. Differential expression was examined between CHR and UC using logistic regression. Psychosocial functioning was measured using the Global Assessment of Functioning scale (GAF). Symptoms were measured using the subscale scores from the Scale of Psychosis-risk Symptoms; Positive, Negative, General, and Disorganised. Three measures of each outcome were included: Baseline, longest available follow-up (last follow-up) and most severe follow-up (MSF). Associations between the proteomic data, GAF and symptoms were assessed using ordinal regression.
RESULTS RESULTS
Of the 99 proteins quantified, six were differentially expressed between UC and CHR. However, only haptoglobin (HP) survived FDR-correction (OR:1.45, 95 %CI:1.23-1.69, p
CONCLUSION CONCLUSIONS
We demonstrate that elevated HP is robustly observed in those at CHR for psychosis, irrespective of transition to psychosis. HP is longitudinally associated with poorer functioning and greater symptom severity. These results agree with previous reports of increased HP gene expression in individuals at-risk for psychosis and with the dysfunction of the acute phase inflammatory response seen in psychotic disorders.

Identifiants

pubmed: 38219978
pii: S0889-1591(23)00401-4
doi: 10.1016/j.bbi.2023.12.018
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Auteurs

Colm Healy (C)

Department of Psychiatry, Royal College of Surgeons in Ireland, Dublin 2, Ireland; Department of Psychology, Royal College of Surgeons in Ireland, Dublin 2, Ireland. Electronic address: colmhealy@rcsi.com.

Jonah Byrne (J)

Department of Psychiatry, Royal College of Surgeons in Ireland, Dublin 2, Ireland.

Subash Raj Suasi (S)

Department of Psychiatry, Royal College of Surgeons in Ireland, Dublin 2, Ireland.

Melanie Föcking (M)

Department of Psychiatry, Royal College of Surgeons in Ireland, Dublin 2, Ireland.

David Mongan (D)

Department of Psychiatry, Royal College of Surgeons in Ireland, Dublin 2, Ireland; School of Medicine Dentistry and Biomedical Science, Queen's University, Belfast Northern Ireland.

Eleftheria Kodosaki (E)

School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Wales United Kingdom.

Meike Heurich-Sevcenco (M)

School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Wales United Kingdom.

Gerard Cagney (G)

University College Dublin, School of Biomolecular and Biomedical Science, Conway Institute Belfield Dublin 4.

Kieran Wynne (K)

University College Dublin, School of Biomolecular and Biomedical Science, Conway Institute Belfield Dublin 4.

Carrie E Bearden (CE)

Semel Institute for Neuroscience and Human Behavior, Departments of Psychiatry and Behavioral Sciences and Psychology, University of California, Los Angeles CA, USA.

Scott W Woods (SW)

Department of Psychiatry, Yale University School of Medicine, New Haven CT, USA.

Barbara Cornblatt (B)

Division of Psychiatry Research, The Zucker Hillside Hospital, Northwell Health, Glen Oaks NY, USA.

Daniel Mathalon (D)

Department of Psychiatry, University of California, and San Francisco Veterans Affairs Medical Center, San Francisco CA, USA.

William Stone (W)

Department of Psychiatry, Harvard Medical School at Beth Israel Deaconess Medical Center and Massachusetts Mental Health Center, Boston MA, USA.

Tyrone D Cannon (TD)

Department of Psychiatry, Yale University School of Medicine, New Haven CT, USA; Department of Psychology, Yale University, New Haven CT, USA.

Jean Addington (J)

Department of Psychiatry, Hotchkiss Brain Institute, University of Calgary, Calgary Canada.

Kristin S Cadenhead (KS)

Department of Psychiatry, UCSD, San Diego CA, USA.

Diana Perkins (D)

Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA.

Clark Jeffries (C)

Renaissance Computing Institute, University of North Carolina, Chapel Hill, NC, USA.

David Cotter (D)

Department of Psychiatry, Royal College of Surgeons in Ireland, Dublin 2, Ireland; Department of Psychiatry, Beaumont Hospital, Dublin 9 Ireland.

Classifications MeSH