The association between cytokines and psychomotor speed in a spectrum of psychotic disorders: A longitudinal study

Jeanette Brun Larsen; Solveig Klæbo Reitan; Else-Marie Løberg; Maria Rettenbacher; Øystein Bruserud; Tor Ketil Larsen; Liss Anda; Christoffer Bartz-Johannessen; Erik Johnsen; Rune A Kroken

doi:10.1016/j.bbih.2021.100392

The association between cytokines and psychomotor speed in a spectrum of psychotic disorders: A longitudinal study

Brain Behav Immun Health. 2021 Nov 23:18:100392. doi: 10.1016/j.bbih.2021.100392. eCollection 2021 Dec.

Authors

Jeanette Brun Larsen^{1

2}, Solveig Klæbo Reitan^{1

2}, Else-Marie Løberg^{3

4

5}, Maria Rettenbacher⁶, Øystein Bruserud^{7

8}, Tor Ketil Larsen^{9

10}, Liss Anda^{4

11}, Christoffer Bartz-Johannessen³, Erik Johnsen^{3

9}, Rune A Kroken^{3

9}

Affiliations

¹ Department of Mental Health, St. Olav's University Hospital, Trondheim, Norway.
² Department of Mental Health, Faculty of Medicine and Health Science, Norwegian University of Science and Technology, Trondheim, Norway.
³ NORMENT, Division of Psychiatry, Haukeland University Hospital, Bergen, Norway.
⁴ Department of Addiction Medicine, Haukeland University Hospital, Bergen, Norway.
⁵ Department of Clinical Psychology, University of Bergen, Bergen, Norway.
⁶ Department of Psychiatry, Psychotherapy and Psychosomatics, Medical University Innsbruck, Innsbruck, Austria.
⁷ Department of Clinical Science, University of Bergen, Bergen, Norway.
⁸ Department of Medicine, Haukeland University Hospital, Bergen, Norway.
⁹ Department of Clinical Medicine, University of Bergen, Bergen, Norway.
¹⁰ Regional Centre for Clinical Research in Psychosis, TIPS, Stavanger University Hospital, Bergen, Norway.
¹¹ Department of Social Studies, University of Stavanger, Stavanger, Norway.

Abstract

Background: In schizophrenia, impaired psychomotor speed is a common symptom predicting worse functional outcome. Inflammation causes changes in white matter integrity, which may lead to reduced psychomotor speed. Therefore, we wanted to investigate if peripheral inflammation assessed with cytokines affected performance on psychomotor speed in patients with a spectrum of psychotic disorders.

Methods: The current study is a prospective cohort study, including participants from a pragmatic, randomised controlled trial comparing three atypical antipsychotics in patients with a spectrum of psychotic disorders. For the purposes of this sub-study, we analysed drug treatment groups collectively. Psychomotor speed was assessed at baseline, and at weeks 6, 12, 26 and 52 of follow-up, using the neuropsychological tests trail making test (TMT) A and B, and symbol coding. Serum concentration of the following cytokines were measured: interleukin (IL)-β, IL-2, IL-4, IL-6, IL-10, IL12 p70, IL-17a, interferon (IFN)-γ and tumor necrosis factor (TNF)-α. Blood samples were collected at baseline and after 1, 3, 6, 12, 26, 39 and 52 weeks. We analysed the effect of cytokines levels on psychomotor speed over time in linear mixed effects models.

Results: In our linear mixed effects models controlling for possible confounders, IFN-γ had a significant negative effect on TMT-A and symbol coding performance. None of the other tests for psychomotor speed were significantly associated with cytokines. Overall psychomotor speed performance increased significantly across the study period while cytokine levels remained stable.

Conclusion: Our study indicates a negative association between IFN-γ and psychomotor speed, which might be of importance when understanding the mechanisms behind psychomotor deviations in psychotic disorders.

Keywords: BMI, body mass index; Cognition; Cytokines; IL, interleukin; Immune markers; Inflammation; MRI, magnetic resonance imaging; MS, multiple sclerosis; PANSS, Positive and Negative Syndrome Scale; Psychomotor performance; Psychomotor speed; RCT, randomised controlled trial; SCID-I, Structured Clinical Interview for DSM-IV Axis I Disorders; Schizophrenia; TMT, Trail Making Test; TNF, tumor necrosis factor; hs-CRP, high-sensitivity C-reactive protein.