Microglial Dysregulation in Psychiatric Disease

Abstract

Microglia, the brain's resident immune cells, are phagocytes of the macrophage lineage that have a key role in responding to inflammation and immune challenge in the brain. More recently, they have been shown to have a number of important roles beyond immune surveillance and response, including synaptic pruning during development and the support of adult neurogenesis. Microglial abnormalities have been found in several neuropsychiatric conditions, though in most cases it remains unclear whether these are causative or are a reaction to some other underlying pathophysiology. Here we summarize postmortem, animal, neuroimaging, and other evidence for microglial pathology in major depression, schizophrenia, autism, obsessive-compulsive disorder, and Tourette syndrome. We identify gaps in the existing literature and important areas for future research. If microglial pathology proves to be an important causative factor in these or other neuropsychiatric diseases, modulators of microglial function may represent a novel therapeutic strategy.

A review of the relationship between proinflammatory cytokines and major depressive disorder

“…A review (Frick et al, 2013) detailing studies concerning cytokine effects on different immune cells indicated that data on microglial dysregulation are "limited" and reported mixed results relating to increased microglial densities and activation in diagnosed MDD patients in both clinical and post-mortem examinations. However, the review also found that aggregated animal studies commonly implicated microglial activation with depressive phenotypes in rats that undergo chronic psychological stress, neonatal LPS injection, and mice with CX3CR1 (fractalkine receptor) deficiencies.…”

Pharmacokinetic Analysis of 11C-PBR28 in the Rat Model of Herpes Encephalitis: Comparison with (R)-11C-PK11195

“…Mi croglia are the resident macrophages of the central nervous system (1). These immune cells are activated by inflammatory stimuli, such as pathogens or neuronal damage, and initiate a cascade of inflammatory responses.…”

Kinins and microglial responses in bipolar disorder: a neuroinflammation hypothesis

“…The presence of dysregulated microglia is evident in the development of psychiatric disorders, such as schizophrenia, anxiety and major depression disorder (Frick et al, 2013;Réus et al, 2015), and an increase in microglial density correlates with suicide rates of different neuropsychiatric disorders (Mondelli et al, 2015). Emerging evidences point the possible role of microglial in BD pathology as inducers of neuroinflammation via kynurenine pathway.…”

“…On the other hand, Frick and coworkers proposed different functions of microglia in psychiatric disorders (Frick et al, 2013), such as alterations in microglial function at sites where neurogenesis, neuronal function and homeostasis are affected, leading to either neuronal or synaptic dysfunctions instead of neurodegeneration. However, the exact involvement of microglial cells in psychiatric disorders remains very debatable.…”