Recent cannabis use affects the association between baseline immune markers and long-term outcomes in psychosis

Abstract Aberrant levels of blood markers reflecting inflammation and immune system activation have been implicated in psychotic disorders and linked to psychotic symptom severity. However, their predictive value for the long-term course of psychotic symptoms as well as the potential confounding and...

Full description

Saved in:
Bibliographic Details
Main Authors: Isabel Kreis, Kristin Fjelnseth Wold, Gina Åsbø, Camilla Bärthel Flaaten, Magnus Johan Engen, Siv Hege Lyngstad, Line Hustad Widing, Mashhood Ahmed Sheikh, Maren Caroline Frogner Werner, Eivind Bakken, Thor Ueland, Nils Eiel Steen, Ingrid Melle
Format: Article
Language:English
Published: Nature Publishing Group 2025-08-01
Series:Translational Psychiatry
Online Access:https://doi.org/10.1038/s41398-025-03498-x
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849388857501417472
author Isabel Kreis
Kristin Fjelnseth Wold
Gina Åsbø
Camilla Bärthel Flaaten
Magnus Johan Engen
Siv Hege Lyngstad
Line Hustad Widing
Mashhood Ahmed Sheikh
Maren Caroline Frogner Werner
Eivind Bakken
Thor Ueland
Nils Eiel Steen
Ingrid Melle
author_facet Isabel Kreis
Kristin Fjelnseth Wold
Gina Åsbø
Camilla Bärthel Flaaten
Magnus Johan Engen
Siv Hege Lyngstad
Line Hustad Widing
Mashhood Ahmed Sheikh
Maren Caroline Frogner Werner
Eivind Bakken
Thor Ueland
Nils Eiel Steen
Ingrid Melle
author_sort Isabel Kreis
collection DOAJ
description Abstract Aberrant levels of blood markers reflecting inflammation and immune system activation have been implicated in psychotic disorders and linked to psychotic symptom severity. However, their predictive value for the long-term course of psychotic symptoms as well as the potential confounding and moderating role of cannabis use remain underexplored. We tested if baseline levels of immune markers previously linked to psychotic symptoms or treatment response (CRP, IL-1RA, sIL-2R, sTNFR1, sgp130) predicted 10-year outcomes in a first-episode psychosis sample (N = 320), and whether associations were moderated by baseline cannabis use. We assessed psychiatric (re)admissions and number of psychotic episodes during each year of the follow-up period, as well as change in positive psychotic symptom severity from baseline. Apart from sTNFR1, none of the immune markers significantly predicted psychosis outcomes independently of cannabis use. Baseline sTNFR1 was linked to lower risk of both (re)admissions and psychotic episodes, with an increasingly negative association over time. The statistical effects of CRP, IL-1RA, and sgp130 were all dependent on cannabis use. Specifically, negative (CRP, IL-1RA) or positive associations (sgp130) with psychiatric (re)admission risk or psychotic episode risk were observed in cannabis users only. Similarly, sgp130 was negatively associated with symptom change in cannabis users only. Some of these associations varied by follow-up year of the measured outcome (sgp130, IL-1RA). These findings challenge the prognostic and etiological significance of baseline immune markers for the course of positive psychotic symptoms and emphasize the importance of accounting for cannabis use.
format Article
id doaj-art-727ff088e8b94a33aec6f8ca6649cb73
institution Kabale University
issn 2158-3188
language English
publishDate 2025-08-01
publisher Nature Publishing Group
record_format Article
series Translational Psychiatry
spelling doaj-art-727ff088e8b94a33aec6f8ca6649cb732025-08-20T03:42:07ZengNature Publishing GroupTranslational Psychiatry2158-31882025-08-0115111110.1038/s41398-025-03498-xRecent cannabis use affects the association between baseline immune markers and long-term outcomes in psychosisIsabel Kreis0Kristin Fjelnseth Wold1Gina Åsbø2Camilla Bärthel Flaaten3Magnus Johan Engen4Siv Hege Lyngstad5Line Hustad Widing6Mashhood Ahmed Sheikh7Maren Caroline Frogner Werner8Eivind Bakken9Thor Ueland10Nils Eiel Steen11Ingrid Melle12Centre for Precision Psychiatry, Institute of Clinical Medicine, Faculty of Medicine, University of OsloSection for Clinical Psychosis Research, Department of Research and Innovation, Division of Mental Health and Addiction, Oslo University HospitalSection for Clinical Psychosis Research, Department of Research and Innovation, Division of Mental Health and Addiction, Oslo University HospitalSection for Clinical Psychosis Research, Department of Research and Innovation, Division of Mental Health and Addiction, Oslo University HospitalNydalen District Psychiatric Center, Division of Mental Health and Addiction, Oslo University HospitalNydalen District Psychiatric Center, Division of Mental Health and Addiction, Oslo University HospitalSection for Clinical Psychosis Research, Department of Research and Innovation, Division of Mental Health and Addiction, Oslo University HospitalResearch Institute of Internal Medicine, Oslo University Hospital, RikshospitaletDivision of Clinical Neuroscience, Department of Research and Innovation, Oslo University HospitalSection for Precision Psychiatry, Department of Research and Innovation, Division of Mental Health and Addiction, Oslo University HospitalInstitute of Clinical Medicine, University of OsloCentre for Precision Psychiatry, Institute of Clinical Medicine, Faculty of Medicine, University of OsloSection for Clinical Psychosis Research, Department of Research and Innovation, Division of Mental Health and Addiction, Oslo University HospitalAbstract Aberrant levels of blood markers reflecting inflammation and immune system activation have been implicated in psychotic disorders and linked to psychotic symptom severity. However, their predictive value for the long-term course of psychotic symptoms as well as the potential confounding and moderating role of cannabis use remain underexplored. We tested if baseline levels of immune markers previously linked to psychotic symptoms or treatment response (CRP, IL-1RA, sIL-2R, sTNFR1, sgp130) predicted 10-year outcomes in a first-episode psychosis sample (N = 320), and whether associations were moderated by baseline cannabis use. We assessed psychiatric (re)admissions and number of psychotic episodes during each year of the follow-up period, as well as change in positive psychotic symptom severity from baseline. Apart from sTNFR1, none of the immune markers significantly predicted psychosis outcomes independently of cannabis use. Baseline sTNFR1 was linked to lower risk of both (re)admissions and psychotic episodes, with an increasingly negative association over time. The statistical effects of CRP, IL-1RA, and sgp130 were all dependent on cannabis use. Specifically, negative (CRP, IL-1RA) or positive associations (sgp130) with psychiatric (re)admission risk or psychotic episode risk were observed in cannabis users only. Similarly, sgp130 was negatively associated with symptom change in cannabis users only. Some of these associations varied by follow-up year of the measured outcome (sgp130, IL-1RA). These findings challenge the prognostic and etiological significance of baseline immune markers for the course of positive psychotic symptoms and emphasize the importance of accounting for cannabis use.https://doi.org/10.1038/s41398-025-03498-x
spellingShingle Isabel Kreis
Kristin Fjelnseth Wold
Gina Åsbø
Camilla Bärthel Flaaten
Magnus Johan Engen
Siv Hege Lyngstad
Line Hustad Widing
Mashhood Ahmed Sheikh
Maren Caroline Frogner Werner
Eivind Bakken
Thor Ueland
Nils Eiel Steen
Ingrid Melle
Recent cannabis use affects the association between baseline immune markers and long-term outcomes in psychosis
Translational Psychiatry
title Recent cannabis use affects the association between baseline immune markers and long-term outcomes in psychosis
title_full Recent cannabis use affects the association between baseline immune markers and long-term outcomes in psychosis
title_fullStr Recent cannabis use affects the association between baseline immune markers and long-term outcomes in psychosis
title_full_unstemmed Recent cannabis use affects the association between baseline immune markers and long-term outcomes in psychosis
title_short Recent cannabis use affects the association between baseline immune markers and long-term outcomes in psychosis
title_sort recent cannabis use affects the association between baseline immune markers and long term outcomes in psychosis
url https://doi.org/10.1038/s41398-025-03498-x
work_keys_str_mv AT isabelkreis recentcannabisuseaffectstheassociationbetweenbaselineimmunemarkersandlongtermoutcomesinpsychosis
AT kristinfjelnsethwold recentcannabisuseaffectstheassociationbetweenbaselineimmunemarkersandlongtermoutcomesinpsychosis
AT ginaasbø recentcannabisuseaffectstheassociationbetweenbaselineimmunemarkersandlongtermoutcomesinpsychosis
AT camillabarthelflaaten recentcannabisuseaffectstheassociationbetweenbaselineimmunemarkersandlongtermoutcomesinpsychosis
AT magnusjohanengen recentcannabisuseaffectstheassociationbetweenbaselineimmunemarkersandlongtermoutcomesinpsychosis
AT sivhegelyngstad recentcannabisuseaffectstheassociationbetweenbaselineimmunemarkersandlongtermoutcomesinpsychosis
AT linehustadwiding recentcannabisuseaffectstheassociationbetweenbaselineimmunemarkersandlongtermoutcomesinpsychosis
AT mashhoodahmedsheikh recentcannabisuseaffectstheassociationbetweenbaselineimmunemarkersandlongtermoutcomesinpsychosis
AT marencarolinefrognerwerner recentcannabisuseaffectstheassociationbetweenbaselineimmunemarkersandlongtermoutcomesinpsychosis
AT eivindbakken recentcannabisuseaffectstheassociationbetweenbaselineimmunemarkersandlongtermoutcomesinpsychosis
AT thorueland recentcannabisuseaffectstheassociationbetweenbaselineimmunemarkersandlongtermoutcomesinpsychosis
AT nilseielsteen recentcannabisuseaffectstheassociationbetweenbaselineimmunemarkersandlongtermoutcomesinpsychosis
AT ingridmelle recentcannabisuseaffectstheassociationbetweenbaselineimmunemarkersandlongtermoutcomesinpsychosis