Depression as a Microglial Disease

Inflammation: A Contributor to Depressive Comorbidity in Inflammatory Skin Disease

“…Although inflammation may be local, arising in peripheral organs, pro-inflammatory cytokines such as TNF-α and IL-6, but also dendritic cells, can cross the blood-brain barrier (BBB) and trigger a cascade of events in the central nervous system [21]. The integrity of the BBB can be compromised due to stress, leading to a "leaky BBB" which does not adequately protect the brain from peripheral cytokine infiltration [22]. An overactive stress response [23] and elevated levels of peripheral cytokines can lead to brain cytokine signaling with downstream effects on synaptic function via the actions of the microglia, neurotransmitter metabolism, and neurogenesis [22].…”

“…The integrity of the BBB can be compromised due to stress, leading to a "leaky BBB" which does not adequately protect the brain from peripheral cytokine infiltration [22]. An overactive stress response [23] and elevated levels of peripheral cytokines can lead to brain cytokine signaling with downstream effects on synaptic function via the actions of the microglia, neurotransmitter metabolism, and neurogenesis [22]. For example, increased levels of TNF-α accelerate the breakdown of neurotransmitters, such as serotonin, by increasing the activity of the enzyme indoleamine 2,3-dioxygenase [24].…”

Microglial Gene Expression Alterations in the Brains of Patients with Psychiatric Disorders

“…Microglial activation has been observed in postmortem brains from patients with psychiatric disorders, including schizophrenia [20], mood disorders [21,22], substance abuse [23], and suicidality [24]. However, detailed mechanisms of microglia involvement in the pathogeneses of psychiatric disorders have not been elucidated.…”

“…Because evidence supports microglial involvement in the pathogeneses of depression, Yirmiya, RN et al proposed that depression is a microglial disease [21]. A postmortem study demonstrated strong activation of HLA-DR-positive microglia in an old, affective disorder patient by immunohistochemistry [20].…”

Trained innate immunity: a salient factor in the pathogenesis of neuroimmune psychiatric disorders

“…10,11 These cells are strongly implicated in the pathogenesis of neuropsychiatric disorders therefore. [12][13][14] Over the past decades, the major difference between the adaptive and innate immune systems has been considered the ability of the adaptive immune system to retain memory for specific infectious agents, whilst the innate immune system has been considered neither capable of memory nor specificity. 15 This memory function of the adaptive immune system is critical to immunity in vertebrates, often offering lifelong protection against re-infection.…”