학술논문
Differential expression of haptoglobin in individuals at clinical high risk of psychosis and its association with global functioning and clinical symptoms.
Document Type
Academic Journal
Author
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.; Byrne J; Department of Psychiatry, Royal College of Surgeons in Ireland, Dublin 2, Ireland.; Raj Suasi S; Department of Psychiatry, Royal College of Surgeons in Ireland, Dublin 2, Ireland.; Föcking M; Department of Psychiatry, Royal College of Surgeons in Ireland, Dublin 2, Ireland.; 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.; Kodosaki E; School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Wales United Kingdom.; Heurich M; School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Wales United Kingdom.; Cagney G; University College Dublin, School of Biomolecular and Biomedical Science, Conway Institute Belfield Dublin 4.; Wynne K; University College Dublin, School of Biomolecular and Biomedical Science, Conway Institute Belfield Dublin 4.; Bearden CE; Semel Institute for Neuroscience and Human Behavior, Departments of Psychiatry and Behavioral Sciences and Psychology, University of California, Los Angeles CA, USA.; Woods SW; Department of Psychiatry, Yale University School of Medicine, New Haven CT, USA.; Cornblatt B; Division of Psychiatry Research, The Zucker Hillside Hospital, Northwell Health, Glen Oaks NY, USA.; Mathalon D; Department of Psychiatry, University of California, and San Francisco Veterans Affairs Medical Center, San Francisco CA, USA.; Stone W; Department of Psychiatry, Harvard Medical School at Beth Israel Deaconess Medical Center and Massachusetts Mental Health Center, Boston MA, USA.; Cannon TD; Department of Psychiatry, Yale University School of Medicine, New Haven CT, USA; Department of Psychology, Yale University, New Haven CT, USA.; Addington J; Department of Psychiatry, Hotchkiss Brain Institute, University of Calgary, Calgary Canada.; Cadenhead KS; Department of Psychiatry, UCSD, San Diego CA, USA.; Perkins D; Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA.; Jeffries C; Renaissance Computing Institute, University of North Carolina, Chapel Hill, NC, USA.; Cotter D; Department of Psychiatry, Royal College of Surgeons in Ireland, Dublin 2, Ireland; Department of Psychiatry, Beaumont Hospital, Dublin 9 Ireland.
Source
Publisher: Elsevier Country of Publication: Netherlands NLM ID: 8800478 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2139 (Electronic) Linking ISSN: 08891591 NLM ISO Abbreviation: Brain Behav Immun Subsets: MEDLINE
Subject
Language
English
Abstract
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: 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: 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, padj = <0.001). HP was cross-sectionally and longitudinally associated with functioning and symptoms such that higher HP values were associated with poorer functioning and more severe symptoms. Results were evident after stringent adjustment and poorer functioning was observed in both NAPLS cohort separately.
Conclusion: 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.
Competing Interests: 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.
(Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
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: 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: 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.
Competing Interests: 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.
(Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)