Cytokines and psychiatric symptoms in patients receiving inpatient treatment: The relationship between changes in immune activation and symptoms of mental distress. A 12-week follow-up study of patients with mental health disorders

Categories: Research project completed

Nyhetsartikkel publisert 30/01/24

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Patients with common psychiatric diseases like mood disorders and anxiety disorders have often been found to exhibit chronically elevated levels of pro- and anti-inflammatory cytokines when compared to healthy people. Studies have found such associations in cross-sectional assessments, but little is known about how the relationship between cytokines and psychiatric symptom change over time in patients receiving inpatient treatment. It is also unclear if psychiatric diseases precede chronic inflammation, or if chronic inflammation precedes psychiatric diseases, although increasing evidence suggests a bidirectional loop. In addition, the use of anti-inflammatory drugs could mediate such associations.

Author: Helge Toft

Helge Toft  is a clinical psychologist specialized in clinical psychology for adults with additional training in anxiety and trauma disorders. Tuva’s areas of interest include anxiety disorders, trauma disorders, cognitive behaviour therapy and advanced statistics.  Tuva has developed expertise in analyzing longitudinal data using advanced latent growth curve models.

About the Project

Despite the need for empirical investigations of shame in the context of trauma, methodological problems regarding the available assessments of shame and the need for developing assessment of shame in the context of trauma, there is no such assessment available. Accordingly, an assessment of trauma-related shame called the trauma-related shame inventory was first constructed.

This dissertation incorporate both 1) evaluation of the psychometric properties of trauma-related shame inventory (the first article), and 2 a) examining the relationship of trauma-related shame and guilt and symptoms of PTSD (the second article), and b) empirical evaluation of trauma-related shame and guilt as maintaining factors of PTSD symptoms during treatment in a RCT (the third article). In addition, the present thesis also includes an empirical investigation of the process of changes in trauma-related shame and guilt with symptoms of PTSD were similar or different in two treatment conditions of trauma-focused therapies, prolonged exposure and modified prolonged exposure, in which imagery rescripting replaces imagery exposure.


The overall aim of her dissertation was to provide empirical investigation of whether trauma-related shame and guilt are part of the internal domain of the PTSD construct as provided in the DSM-5. This doctoral thesis aimed to investigate the levels and trajectories of cytokines IL-1β, IL-1RA, MCP-1 and TNF-α and psychiatric symptoms as measured by SCL-90R GSI and BDI-II in a mixed sample of psychiatric patients across 12 weeks of inpatient treatment at Modum Bad Psychiatric Center. The use of anti-inflammatory drugs was taken into account.


Patients diagnosed with Post-traumatic stress disorder had higher cytokine levels and showed a more severe development in cytokine levels across the treatment period than patients with depression, anxiety or eating disorder. The cytokines in patients without PTSD were either unchanged or showed decreasing levels across time. Regardless of diagnosis, most patients benefited from treatment, as reported by lower GSI scores at discharge. The levels of IL-1RA and MCP-1 were not associated with the trajectory of psychiatric symptom scores across time, but were associated with psychiatric symptom level. This result was only present in patients who did not use anti-inflammatory drugs, possibly suggesting a mediating effect of such drugs on psychiatric symptoms for patients in treatment.


The project is a doctoral research project that began in 2016 and finished up in 2020. The project used data from all the Units at Modum Bad.


The project was funded by Inland Norway University of Applied Sciences


The study uses data collected continuously throughout the treatment process at Modum Bad via the feedback instrument M-POQ (Modum Bad Process and Outcome Questionnaire).

Contact Information

Project Manager: Terje Tilden

Project contact: Helge Toft   (

You can also reach us through the Modum Bad telephone service: 32 74 97 00.

Project participants

Bruce Wampold, Ph.D., University of Wisconsin 

Jørgen Bramness, University of Tromsø


Paper I. Toft H, Neupane SP, Bramness JG, Tilden T, Wampold BE, Lien L. The effect of trauma and alcohol on the relationship between level of cytokines and depression among patients entering psychiatric treatment. BMC Psychiatry. 2018;18(1):95. DOI: 10.1186/s12888-018-1677-z.. The article is included in the thesis. Also available in DUO:

Paper II. Toft H, Bramness JG, Lien L, Abebe DS, Wampold BE, Tilden T, et al. PTSD patients show increasing cytokine levels during treatment despite reduced psychological distress. Neuropsychiatr Dis Treat. 2018;14:2367-78. DOI: 10.2147/NDT.S173659. The article is included in the thesis. Also available at:

Paper III. Toft H, Lien L, Neupane SP, Abebe DS, Tilden T, Wampold BE, et al. Cytokine concentrations are related to level of mental distress in inpatients not using antiinflammatory drugs. Acta Neuropsychiatr. 2019:1-22. DOI: 10.1017/neu.2019.36. The article is included in the thesis. Also available at:

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