liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Multivariate analyses of immune markers reveal increases in plasma EN-RAGE in first-episode psychosis patients
Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping.ORCID iD: 0000-0002-1837-5930
Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.ORCID iD: 0000-0002-0201-273X
Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.ORCID iD: 0000-0001-5034-9110
5 Institute of Clinical Medicine University of Tartu; Psychiatry Clinic of Tartu University Hospital, Tartu, Estonia.ORCID iD: 0000-0003-3028-7826
Show others and affiliations
2023 (English)In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 13, no 1, article id 326Article in journal (Refereed) Published
Abstract [en]

Immune cells and cytokines are largely recognized as significant factors in the pathophysiology of neuropsychiatric disorders. The possible role of other blood cells such as leukocytes in events of acute psychosis is in contrast only emerging. To study blood-born markers in acute psychosis we here evaluated plasma proteins in drug-naive first-episode psychosis (FEP) patients and healthy controls using a multiplex proximity extension assay technique. We analyzed a panel of 92 immune markers and plasma samples from 60 FEP patients and 50 controls and evaluated the changes obtained using multivariate statistical methods followed by protein pathway analyses. Data showed that 11 proteins are significantly different between FEP patients and healthy controls We observed increases in pro-inflammatory proteins such as interleukin-6, oncostatin-M, and transforming growth factor-alpha in FEP patients compared with controls. Likewise, the extracellular newly identified RAGE-binding protein (EN-RAGE) that regulates the expression of various cytokines was also elevated in the plasma of FEP patients. The results indicate that neutrophil-derived EN-RAGE could play an important role during the early phase of acute psychosis by stimulating cytokines and the immune response targeting thereby likely also the brain vasculature.

Place, publisher, year, edition, pages
Springer, 2023. Vol. 13, no 1, article id 326
National Category
Psychiatry
Identifiers
URN: urn:nbn:se:liu:diva-198695DOI: 10.1038/s41398-023-02627-8ISI: 001088122700001OAI: oai:DiVA.org:liu-198695DiVA, id: diva2:1806618
Funder
Swedish Research CouncilEuropean Regional Development Fund (ERDF)
Note

Funding agencies: Supported by H2020-MSCA-RISE-2016 (EU Grant no: 73479), The Finnish Society of Sciences and Letters, The Swedish Research Council (2018-02623, 2019-05820), Region Östergötland (LIO-795611, LIO-897641), Region South-East Sweden (FORSS807001, FORSS-849051, Swedish Brain Foundation (Hjärnfonden), Liv and Hälsa Foundation, Finska Läkaresällskapet, Magnus Ehrnrooth Foundation, Sigrid Jusélius Foundation, Minerva Foundation, European Regional Development Fund (Project No.2014-2020.4.01.15-0012), and Estonian Research Foundation (PUT PRG685). Open access funding provided by Linköping University. 

Available from: 2023-10-23 Created: 2023-10-23 Last updated: 2024-01-17
In thesis
1. Immunological Changes and Brain Function over a Psychotic-Depressive Spectrum
Open this publication in new window or tab >>Immunological Changes and Brain Function over a Psychotic-Depressive Spectrum
2023 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Psychotic and depressive disorders are severe psychiatric disorders that contribute significantly to the global burden of disease. They are distinct disorders with different symptom profiles according to both the Diagnostic and Statistical Manual and the International Classification of Diseases. However, these disorders share commonalities in various aspects, such as high comorbidity, prevalence of subclinical symptoms, and shared genetics. Furthermore, both disorders have been associated with a dysregulated immune system functioning.

In this thesis, we aimed to identify common biological dimensions of both depression and psychosis by first investigating proteins related to immune system activation in depression and psychosis separately, and then identifying biological underpinnings of psychotic-like symptoms in depression.Specifically, we first assessed in major depressive disorder central nervous system levels of metabolites along the kynurenine pathway, a pathway that is regulated by the immune system and implicated in depressive and psychotic disorders (paper I). We found an imbalance between neuroprotective versus neurotoxic metabolites in blood and decreased levels of a neuroprotective metabolite in cerebrospinal fluid of patients with depression.

Next, we assessed patterns of proteins implicated in immune-system function that distinguish first episode psychosis and healthy controls (paper II). Results indicate prominent changes in patients compared to controls, partially replicating previous findings and partially highlighting proteins that have not previously been assessed in psychosis.

Lastly, we investigated psychotic-like symptoms in patients with major depressive disorder, finding a relation to immune system markers (paper III) and changes in connectivity between brain structures that integrate information about the physical body and autobiographic information into a sense of self (paper IV).

In summary, the results from this thesis suggest that both in major depressive disorder and first episode psychosis there might be a dysregulation of the immune system and closely related systems such as the kynurenine pathway. These commonalities could further underlie the prevalence of subclinical psychotic-like symptoms in major depressive disorder. Ultimately, a better understanding of the underlying biological mechanisms of psychiatric disorders and, transdiagnostically, their symptoms will help formulate empiricallyinformed frameworks to guide clinical diagnostic processes and treatments.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2023. p. 87
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1867
National Category
Psychiatry
Identifiers
urn:nbn:se:liu:diva-198464 (URN)10.3384/9789180753098 (DOI)9789180753081 (ISBN)9789180753098 (ISBN)
Public defence
2023-11-24, Berzeliussalen, Building 463, Campus US, Linköping, 09:00 (English)
Opponent
Supervisors
Note

Funding agencies: Drottning Silvias Jubileumsfond, Fonden för Psykisk Hälsa, Swedish Research Council, Region Östergötland (ALF), Medical Research Council of Southeast Sweden (ALF), Horizon 2020, Warren Foundation, Johnson & Johnson Innovation, National Institutes of Health, MD Anderson Cancer Support Grant, The Finnish Society of Sciences, Hjärnfonden, Liv and Hälsa Foundation, Finska Läkarsällskapet, Magnus Ehrnrooth Foundation, Sigrid Jusélius Foundation, Minerva Foundation, European Regional Development Fund, Estonian Research Foundation

Available from: 2023-10-13 Created: 2023-10-13 Last updated: 2023-12-28Bibliographically approved

Open Access in DiVA

fulltext(1080 kB)52 downloads
File information
File name FULLTEXT01.pdfFile size 1080 kBChecksum SHA-512
afdc759c7259c06fd2b27f47358d51c3468e9812fed90dd9863741201396c690b8a8b19325c282f910b363fd0dab30fd99caba0a98693e402dbb8a6d1a85a09c
Type fulltextMimetype application/pdf

Other links

Publisher's full text

Authority records

Korhonen, LauraPaul, ElisabethWåhlén, KarinLindholm, Dan

Search in DiVA

By author/editor
Korhonen, LauraPaul, ElisabethWåhlén, KarinHaring, LiinaLindholm, Dan
By organisation
Center for Social and Affective NeuroscienceFaculty of Medicine and Health SciencesDepartment of Child and Adolescent Psychiatry in LinköpingDivision of Prevention, Rehabilitation and Community MedicinePain and Rehabilitation CenterDivision of Neurobiology
In the same journal
Translational Psychiatry
Psychiatry

Search outside of DiVA

GoogleGoogle Scholar
Total: 53 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 254 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf