Microglia and Psychiatric Disorders

TY - CHAP

T1 - Microglia and Psychiatric Disorders

AU - Couch, Amalie C.M.

AU - Vernon, Anthony C.

N1 - Publisher Copyright: © Springer Nature Switzerland AG 2021.

PY - 2021/1/1

Y1 - 2021/1/1

N2 - Immunological, developmental and homeostatic functions are attributed to microglia in the central nervous system (CNS). Supporting this view, transcriptional profiling studies have revealed the myriad of microglial transformation states, with specific functions required at defined spatiotemporal points throughout life. This plasticity can be a double-edged sword, whereby functional outcomes of microglia can shift from neuroprotective to neurotoxic, if their homeostasis becomes dysregulated, leading to their implication in the pathology of numerous brain disorders. In this context, the depletion of microglia from the rodent brain is sufficient to induce behavioural symptoms with dimensional relevance for some psychiatric brain disorders, including schizophrenia and autism spectrum disorder. In this chapter, we therefore consider the potential role of microglia in these disorders. In doing so, we present evidence from human genetics, post-mortem tissue studies, epidemiological studies and in vivo positron emission tomography (PET) imaging. In addition, we consider how functional changes in microglia could lead to psychiatric disorders, with a particular focus on the putative role of microglia in developmental synapse formation and elimination. Finally, we address gaps in our knowledge that remain to be filled, specifically the key question of whether microglial pathology is causative for psychiatric symptoms or merely an epiphenomenon of no consequence.

AB - Immunological, developmental and homeostatic functions are attributed to microglia in the central nervous system (CNS). Supporting this view, transcriptional profiling studies have revealed the myriad of microglial transformation states, with specific functions required at defined spatiotemporal points throughout life. This plasticity can be a double-edged sword, whereby functional outcomes of microglia can shift from neuroprotective to neurotoxic, if their homeostasis becomes dysregulated, leading to their implication in the pathology of numerous brain disorders. In this context, the depletion of microglia from the rodent brain is sufficient to induce behavioural symptoms with dimensional relevance for some psychiatric brain disorders, including schizophrenia and autism spectrum disorder. In this chapter, we therefore consider the potential role of microglia in these disorders. In doing so, we present evidence from human genetics, post-mortem tissue studies, epidemiological studies and in vivo positron emission tomography (PET) imaging. In addition, we consider how functional changes in microglia could lead to psychiatric disorders, with a particular focus on the putative role of microglia in developmental synapse formation and elimination. Finally, we address gaps in our knowledge that remain to be filled, specifically the key question of whether microglial pathology is causative for psychiatric symptoms or merely an epiphenomenon of no consequence.

KW - Autism spectrum disorder

KW - Common risk variants

KW - Microglia

KW - Neurodevelopmental disorder

KW - Neuroinflammation

KW - Post-mortem study

KW - Psychiatric disorders

KW - Schizophrenia

KW - Synaptic pruning

KW - Translocator protein

UR - http://www.scopus.com/inward/record.url?scp=85142244114&partnerID=8YFLogxK

U2 - 10.1007/978-3-030-71229-7_8

DO - 10.1007/978-3-030-71229-7_8

M3 - Chapter

AN - SCOPUS:85142244114

SN - 9783030712280

SP - 133

EP - 158

BT - Immuno-Psychiatry

PB - Springer International Publishing

ER -