Cytokines in psychosis: from mechanism towards treatment and prediction

Identifying risk factors that distinguish disease onset from chronicity is crucial for understanding potential causal mechanisms and to devise effective strategies for treatment, prevention, and prediction. Studies of peripheral blood concentrations of inflammatory markers, such as cytokines (eg, interleukin [IL]-6) and acute-phase proteins (eg, C-reactive protein), have provided some of the most consistent evidence implicating low-grade systemic inflammation in schizophrenia and related psychotic disorders. 1 Khandaker GM Cousins L Deakin J Lennox BR Yolken R Jones PB Inflammation and immunity in schizophrenia: implications for pathophysiology and treatment. Lancet Psychiatry. 2015; 2: 258-270 Summary Full Text Full Text PDF PubMed Scopus (513) Google Scholar These studies have hitherto been subject to several systematic reviews and meta-analyses. 2 Upthegrove R Manzanares-Teson N Barnes NM Cytokine function in medication-naive first episode psychosis: a systematic review and meta-analysis. Schizophr Res. 2014; 155: 101-108 Crossref PubMed Scopus (333) Google Scholar , 3 Goldsmith DR Rapaport MH Miller BJ A meta-analysis of blood cytokine network alterations in psychiatric patients: comparisons between schizophrenia, bipolar disorder and depression. Mol Psychiatry. 2016; 21: 1696-1709 Crossref PubMed Scopus (957) Google Scholar In this issue of The Lancet Psychiatry, Sean Halstead and colleagues 4 Halstead S Siskind D Amft M et al. Alteration patterns of peripheral concentrations of cytokines and associated inflammatory proteins in acute and chronic stages of schizophrenia: a systematic review and network meta-analysis. Lancet Psychiatry. 2023; (published online Feb 27.)https://doi.org/10.1016/S2215-0366(23)00025-1 Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar add to this evidence base through a systematic review and meta-analysis of blood inflammatory marker alterations in patients with acute and chronic schizophrenia-spectrum disorder. Alteration patterns of peripheral concentrations of cytokines and associated inflammatory proteins in acute and chronic stages of schizophrenia: a systematic review and network meta-analysisResults suggest that people with schizophrenia-spectrum disorders have a baseline level of inflammatory protein alteration throughout the illness, as reflected by consistently elevated pro-inflammatory proteins, hypothesised here as trait markers (eg, IL-6), while those with acute psychotic illness might have superimposed immune activity with increased concentrations of hypothesised state markers (eg, IFN-γ). Further research is required to determine whether these peripheral alterations are reflected within the central nervous system. Full-Text PDF Integrating inflammationMental health disorders can be understood on various levels, from the phenomenological to the neurobiological. In parallel, they are considered to arise through a wide range of influences, from a person's social environment to their genetics and neurodevelopment. Integrating these elements into one complex picture of psychopathology is increasingly challenging. In this issue, Ana Gómez-Carrillo and colleagues introduce a cultural–ecosocial framework, challenging the idea that physiological processes are the only true causal explanation of illness. Full-Text PDF