Network Analysis of Inflammation and Symptoms in Recent Onset Schizophrenia and the Influence of Minocycline During a Clinical Trial

Stephen Wood, Golam M. Khandaker, Paola Dazzan, Carmine Pariante, Nicholas Barnes, Naghmeh Nikkheslat, Rachel C Vincent, Alex Roberts, Annalisa Giordano, Andrew Watson, John Suckling, Thomas R. E. Barnes, Nusrat Husain, Peter B. Jones, Eileen M. Joyce, Stephen M Lawrie, Shon W Lewis, Bill Deakin, Rachel Upthegrove

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Abstract

Background: Attempts to delineate an immune subtype of schizophrenia have not yet led to the clear identification of potential treatment targets. An unbiased informatic approach at the level of individual immune cytokines and symptoms may reveal organisational structures underlying heterogeneity in schizophrenia, and potential for future therapies. Objectives: To determine the network and relative influence of pro- and anti-inflammatory cytokines on depressive, positive, and negative symptoms. We further aimed to determine the effect of exposure to minocycline or placebo for 6 months on cytokine-symptom network connectivity and structure. Method: Network analysis was applied to baseline and six-month data from the large multi-center BeneMin trial of minocycline (N=207) in schizophrenia. Results: Proinflammatory
cytokines IL-6, TNF-α, and IFN-γ had the greatest influence in the inflammatory network and were associated with depressive symptoms and suspiciousness at
baseline. At 6 months (?)the placebo group network connectivity was 57% stronger than the minocycline group, due to significantly greater influence of TNF-α, early wakening, and pathological guilt. Conclusions: IL-6 and its downstream impact on TNF-α, and IFN-γ, could offer novel targets for treatment if offered at the relevant phenotypic profile including those with depression. Future targeted experimental studies of immune-based therapies are now needed
Original languageEnglish
JournalTranslational psychiatry
Publication statusAccepted/In press - 20 May 2023

Keywords

  • Schizophrenia
  • Inflammation
  • Symptoms
  • Network
  • Cytokines
  • Immunology

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