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

TY - JOUR

T1 - Network Analysis of Inflammation and Symptoms in Recent Onset Schizophrenia and the Influence of Minocycline During a Clinical Trial

AU - Wood, Stephen

AU - Khandaker, Golam M.

AU - Dazzan, Paola

AU - Pariante, Carmine

AU - Barnes, Nicholas

AU - Nikkheslat, Naghmeh

AU - Vincent, Rachel C

AU - Roberts, Alex

AU - Giordano, Annalisa

AU - Watson, Andrew

AU - Suckling, John

AU - Barnes, Thomas R. E.

AU - Husain, Nusrat

AU - Jones, Peter B.

AU - Joyce, Eileen M.

AU - Lawrie, Stephen M

AU - Lewis, Shon W

AU - Deakin, Bill

AU - Upthegrove, Rachel

PY - 2023/5/20

Y1 - 2023/5/20

N2 - 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: Proinflammatorycytokines IL-6, TNF-α, and IFN-γ had the greatest influence in the inflammatory network and were associated with depressive symptoms and suspiciousness atbaseline. 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

AB - 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: Proinflammatorycytokines IL-6, TNF-α, and IFN-γ had the greatest influence in the inflammatory network and were associated with depressive symptoms and suspiciousness atbaseline. 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

KW - Schizophrenia

KW - Inflammation

KW - Symptoms

KW - Network

KW - Cytokines

KW - Immunology

M3 - Article

SN - 2158-3188

JO - Translational psychiatry

JF - Translational psychiatry

ER -