Plasma complement and coagulation proteins as prognostic factors of negative symptoms: An analysis of the NAPLS 2 and 3 studies

Byrne, Jonah F., Healy, Colm, Föcking, Melanie, Heurich, Meike ORCID: https://orcid.org/0000-0003-0105-2702, Susai, Subash Raj, Mongan, David, Wynne, Kieran, Kodosaki, Eleftheria, Woods, Scott W., Cornblatt, Barbara A., Stone, William S., Mathalon, Daniel H., Bearden, Carrie E., Cadenhead, Kristin S., Addington, Jean, Walker, Elaine F., Cannon, Tyrone D., Cannon, Mary, Jeffries, Clark, Perkins, Diana and Cotter, David R. 2024. Plasma complement and coagulation proteins as prognostic factors of negative symptoms: An analysis of the NAPLS 2 and 3 studies. Brain, Behavior, and Immunity 119 , pp. 188-196. 10.1016/j.bbi.2024.03.049

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Abstract

Introduction: Negative symptoms impact the quality of life of individuals with psychosis and current treatment options for negative symptoms have limited effectiveness. Previous studies have demonstrated that complement and coagulation pathway protein levels are related to later psychotic experiences, psychotic disorder, and functioning. However, the prognostic relationship between complement and coagulation proteins and negative symptoms is poorly characterised. Methods: In the North American Prodrome Longitudinal Studies 2 and 3, negative symptoms in 431 individuals at clinical high-risk for psychosis (mean age: 18.2, SD 3.6; 42.5 % female) were measured at multiple visits over 2 years using the Scale of Psychosis-Risk Symptoms. Plasma proteins were quantified at baseline using mass spectrometry. Four factors were derived to represent levels of proteins involved in the activation or regulation of the complement or coagulation systems. The relationships between standardised protein group factors and serial measurements of negative symptoms over time were modelled using generalised least squares regression. Analyses were adjusted for baseline candidate prognostic factors: negative symptoms, positive symptoms, functioning, depressive symptoms, suicidal ideation, cannabis use, tobacco use, antipsychotic use, antidepressant use, age, and sex. Results: Clinical and demographic prognostic factors of follow-up negative symptoms included negative, positive, and depressive symptoms, functioning, and age. Adjusting for all candidate prognostic factors, the complement regulators group and the coagulation regulators group were identified as prognostic factors of follow-up negative symptoms (β: 0.501, 95 % CI: 0.160, 0.842; β: 0.430, 95 % CI: 0.080, 0.780 respectively. The relationship between complement regulator levels and negative symptoms was also observed in NAPLS2 alone (β: 0.501, 95 % CI: −0.037, 1.039) and NAPLS3 alone, additionally adjusting for BMI (β: 0.442, 95 % CI: 0.127, 0.757). Conclusion: The results indicate that plasma complement and coagulation regulator levels are prognostic factors of negative symptoms, independent of clinical and demographic prognostic factors. These results suggest complement and coagulation regulator levels could have potential utility in informing treatment decisions for negative symptoms in individuals at risk.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy
Publisher:	Elsevier
ISSN:	0889-1591
Date of First Compliant Deposit:	22 April 2024
Date of Acceptance:	28 March 2024
Last Modified:	03 May 2024 11:46
URI:	https://orca.cardiff.ac.uk/id/eprint/168202

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