Microglial activation and progressive brain changes in schizophrenia

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 structural brain 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, immune cells resident in the brain, at various stages of the 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 the pathology of grey and white matter. The studies available indicate that 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

Cytokines, Oxidative Stress and Cellular Markers of Inflammation in Schizophrenia.

In this article, we review current evidence linking immune dysfunction in schizophrenia and related psychotic disorders focusing particularly on circulating cytokines, oxidative stress and cellular markers of inflammation in various stages on illness from drug-naïve first episode psychosis to chronic schizophrenia. Acute psychotic episode is associated with low-grade systemic inflammation in some patients, as reflected by increased concentrations of cytokines and other inflammatory markers in peripheral blood. Evidence from general population-based longitudinal cohort studies reporting an association between elevated inflammatory markers in childhood/adolescence and risk of schizophrenia and related psychosis subsequently in adulthood suggest that inflammation could be a causal risk factor for psychosis rather than simply be a consequence of illness. Mendelian randomization studies also suggest that associations between IL-6, CRP and schizophrenia are likely to be causal. In addition, we discuss evidence for disruptions in oxidative stress markers and CSF cytokine levels in schizophrenia, and potential reasons for reported trans-diagnostic associations for inflammatory cytokines including role of early-life adversity/maltreatment. We argue that low-grade inflammation is a clinically useful feature, because it is associated with poor response to antipsychotic medication in first episode psychosis. We discuss clinical implications for immunological understanding of schizophrenia including scope for clinical trials of anti-inflammatory agents and notable gaps in current knowledge, and offer suggestions for future research

Salivary biomarkers for the diagnosis and monitoring of neurological diseases

Current research efforts on neurological diseases are focused on identifying novel disease biomarkers to aid in diagnosis, provide accurate prognostic information and monitor disease progression. With advances in detection and quantification methods in genomics, proteomics and metabolomics, saliva has emerged as a good source of samples for detection of disease biomarkers. Obtaining a sample of saliva offers multiple advantages over the currently tested biological fluids as it is a non-invasive, painless and simple procedure that does not require expert training or harbour undesirable side effects for the patients. Here, we review the existing literature on salivary biomarkers and examine their validity in diagnosing and monitoring neurodegenerative and neuropsychiatric disorders such as autism and Alzheimer\u27s, Parkinson\u27s and Huntington\u27s disease. Based on the available research, amyloid beta peptide, tau protein, lactoferrin, alpha-synuclein, DJ-1 protein, chromogranin A, huntingtin protein, DNA methylation disruptions, and micro-RNA profiles provide display a reliable degree of consistency and validity as disease biomarkers