**1. Introduction**

Microglia is a glial cell that is widely distributed in the central nervous system occupying 10–15% of cells in the brain. Microglia are derived from the mesoderm as well as blood cells and peripheral immune cells. As other cells in the brain are derived from the ectoderm, microglia are similar in nature to peripheral immune cells and play an important role in immune response in the brain. In the steady-state, microglial protrusions are extended in a tree-shape to monitor the intracerebral environment, but when faced with infection, ischemia, exposure to harmful substances, trauma, etc., they are activated and changes morphologically. Activated microglia have enlarged cell bodies, thickened and shortened protrusions, and become amoebic. Microglia move to the target site and release humoral factors such as cytokines and neurotrophic factors [1]. In addition, microglia have a phagocytic

ability similar to peripheral macrophages and have the function of digesting waste products in the brain.

Since 2006, rodent studies that report that stress causes microglial morphological changes in various areas of the brain have been accumulated [2, 3]. It has also been investigated how stress affects the release of cytokines and neurotrophic factors from microglia and the phagocytosis of synapses by microglia. Along with this, imaging studies focusing on microglia have been conducted in humans with stress-related mental disorders. Inflammatory changes in microglia in the human brain can be partially evaluated by positron emission tomography (PET) techniques targeting translocator proteins (TSPO). Depression and posttraumatic stress disorder (PTSD) are representative stress-related psychiatric disorders and are closely associated with suicide. Fibromyalgia is also closely related to stress in its onset and chronicity. Currently, the findings of PET studies targeting TSPO in patients with depression are accumulating, and PET studies targeting patients with PTSD and fibromyalgia have been reported since 2019. A few postmortem studies investigating the association between stress-related mental disorders and microglia have also been conducted.

In this chapter, we first describe the effects of stress on the release of cytokines and neurotrophic factors from microglia and the phagocytosis of synapses by microglia, and their molecular mechanisms. Second, we outline animal and human studies investigating the involvement of microglia in the pathologies of PTSD, depression, suicide, and stress-induced pain.
