title: Microglial Dysregulation in OCD, Tourette Syndrome, and PANDAS.
abstract: There is accumulating evidence that immune dysregulation contributes to the pathophysiology of obsessive-compulsive disorder (OCD), Tourette syndrome, and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS). The mechanistic details of this pathophysiology, however, remain unclear. Here we focus on one particular component of the immune system: microglia, the brain's resident immune cells. The role of microglia in neurodegenerative diseases has been understood in terms of classic, inflammatory activation, which may be both a consequence and a cause of neuronal damage. In OCD and Tourette syndrome, which are not characterized by frank neural degeneration, the potential role of microglial dysregulation is much less clear. Here we review the evidence for a neuroinflammatory etiology and microglial dysregulation in OCD, Tourette syndrome, and PANDAS. We also explore new hypotheses as to the potential contributions of microglial abnormalities to pathophysiology, beyond neuroinflammation, including failures in neuroprotection, lack of support for neuronal survival, and abnormalities in synaptic pruning. Recent advances in neuroimaging and animal model work are creating new opportunities to elucidate these issues.
authors.affiliation: Department of Psychiatry, Yale University, New Haven, CT, USA; 34 Park Street, 3rd floor, W306, New Haven, CT 06519, USA.
authors.forename: Luciana
authors.identifier: 0000-0001-5595-8636
authors.initials: L
authors.lastname: Frick
authors.affiliation: Department of Psychiatry, Yale University, New Haven, CT, USA; 34 Park Street, 3rd floor, W306, New Haven, CT 06519, USA; Department of Psychology, Yale University, New Haven, CT, USA; Department of Interdepartmental Neuroscience Program, Yale University, New Haven, CT, USA; Department of Child Study Center, Yale University, New Haven, CT, USA.
authors.forename: Christopher
authors.identifier: 0000-0003-2117-9321
authors.initials: C
authors.lastname: Pittenger
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000503:physiopathology; D002648:Child; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D017628:Microglia / Q000276:immunology* / Q000502:physiology*; D009771:Obsessive-Compulsive Disorder / Q000209:etiology / Q000276:immunology* / Q000503:physiopathology; D013290:Streptococcal Infections / Q000276:immunology* / Q000503:physiopathology; D005879:Tourette Syndrome / Q000276:immunology* / Q000503:physiopathology