Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

It is well known that schizophrenia is associated with cognitive impairment, reduced cortical grey matter and increased circulating concentrations of inflammatory cytokines. However, the relationship between these findings is not clear. We outline the influential neuroinflammatory hypotheses that raised cytokines provoke a damaging immune response in microglia that results in reduced grey matter and associated cognitive performance. We investigated whether such an interaction might be detectable in the prodromal period as illness emerges from the Clinical High Risk for Psychosis (CHR-P). Meta-analyses suggest that compared with controls, impaired cognition and reduced grey matter are already present by the prodrome and that greater decrements are present in those who later develop symptoms. In contrast, the few cytokine studies report no abnormalities in CHR-P except that interleukin-6 (IL-6) levels were raised versus controls and to a greater extent in the future patients, in one study. We noted that cognitive impairment and less cortical grey matter are more severe in schizophrenia than in affective disorders, but that increased cytokine levels are similarly prevalent across disorders. We found no studies correlating cytokine levels with cognitive impairment in CHR-P but such correlations seem unlikely given the minimal relationship reported in a recent meta-analysis of the many cytokine-cognition studies in established illness. From this and other evidence, we conclude that neuroinflammation is not a core feature of schizophrenia nor a substrate for reduced grey matter volume or cognitive function. We draw attention instead to the emerging evidence that brain-resident immune cells and signalling molecules such as Tregs and IL-6, which are influenced by schizophrenia risk genes, regulate and are necessary for the development and function of neuron-glia interaction. We suggest that cognitive impairment in schizophrenia can be seen as a convergence of genetic and immune-neurodevelopmental dysregulation whereas raised cytokines are a consequence of impaired Tregs control of systemic inflammation.

Original publication

DOI

10.1007/7854_2022_399

Type

Chapter

Publication Date

01/01/2023

Volume

63

Pages

475 - 497