Microglial activation and progressive brain changes in schizophrenia.

Microglial activation and progressive brain changes in schizophrenia.

Br J Pharmacol. 2015 Oct 12;

Authors: Laskaris LE, Di Biase MA, Everall I, Chana G, Christopoulos A, Skafidas E, Cropley VL, Pantelis C

Abstract
Schizophrenia is a debilitating disorder that typically begins in adolescence, and is characterized by perceptual abnormalities, delusions, cognitive and behavioural disturbances and functional impairments. While current treatments can be effective, they are often insufficient to alleviate the full range of symptoms. Schizophrenia is associated with brain structural abnormalities including grey and white matter volume loss and impaired connectivity. Recent findings suggest these abnormalities follow a neuroprogressive course in the earliest stages of the illness, which may be associated with episodes of acute relapse. Neuroinflammation has been proposed as a potential mechanism underlying these brain changes, with evidence of increased density and activation of microglia, the brain's resident immune cells, at various stages of illness. We review evidence for microglial dysfunction in schizophrenia from both neuroimaging and neuropathological data, with a specific focus on studies examining microglial activation in relation to grey and white matter pathology. The available studies indicate the link between microglial dysfunction and brain change in schizophrenia remains an intriguing hypothesis worthy of further examination. Future studies in schizophrenia should: (i) use multimodal imaging to clarify this association by mapping brain changes longitudinally across illness stages in relation to microglial activation, (ii) clarify the nature of microglial dysfunction with markers specific to activation states and phenotypes, (iii) examine the role of microglia and neurons with reference to their overlapping roles in neuroinflammatory pathways and (iv) examine the impact of novel immunomodulatory treatments on brain structure in schizophrenia.

PMID: 26455353 [PubMed - as supplied by publisher]