Neuroinflammation and psychiatric illness

Abstract

Multiple lines of evidence support the pathogenic role of neuroinflammation in psychiatric illness. While systemic autoimmune diseases are well-documented causes of neuropsychiatric disorders, synaptic autoimmune encephalitides with psychotic symptoms often go under-recognized. Parallel to the link between psychiatric symptoms and autoimmunity in autoimmune diseases, neuroimmunological abnormalities occur in classical psychiatric disorders (for example, major depressive, bipolar, schizophrenia, and obsessive-compulsive disorders). Investigations into the pathophysiology of these conditions traditionally stressed dysregulation of the glutamatergic and monoaminergic systems, but the mechanisms causing these neurotransmitter abnormalities remained elusive. We review the link between autoimmunity and neuropsychiatric disorders, and the human and experimental evidence supporting the pathogenic role of neuroinflammation in selected classical psychiatric disorders. Understanding how psychosocial, genetic, immunological and neurotransmitter systems interact can reveal pathogenic clues and help target new preventive and symptomatic therapies.

Inflammation, Glutamate, and Glia: A Trio of Trouble in Mood Disorders

“…Nevertheless, there are several important non-vesicular (non-exocytotic) mechanisms responsible for glutamate release in pathological contexts (Malarkey and Parpura, 2008;Zhou and Danbolt, 2014) including: (1) release through anion channels (Wang et al, 2013a); (2) reverse efflux through EAATs (Ye and Sontheimer, 1996), (3) release by xC transporters as part of the cystine-glutamate exchange process (Lewerenz et al, 2013), (4) astrocytic vesicular glutamate release during gliotransmission (Petrelli and Bezzi, 2016) and release through hemi-channels on astrocytes and microglia (Malarkey and Parpura, 2008). A detailed review of the functioning of these release mechanisms is beyond the scope of this review, and the reader is directed elsewhere (Dantzer and Walker, 2014;Malarkey and Parpura, 2008;Najjar et al, 2013;Tilleux and Hermans, 2007). A brief overview is presented below.…”

Depression in cancer: The many biobehavioral pathways driving tumor progression

“…Those symptoms overlap to some extent with the clinical manifestations of depression and are partly responsive to antidepressant treatments. Thus, the immune cross-talk between the central nervous system (CSM) and the periphery is thought to be largely responsible for the development of somatic and affective symptoms of depression under proinflammatory conditions, while also possibly contributing to carcinogenesis 40 .…”

Dual Role of Superoxide Dismutase 2 Induced in Activated Microglia

“…However, excessive activation of microglia may be harmful to host cells; for example, microglia can promote the development of various neuronal diseases by producing large amounts of inflammatory molecules, such as tumor necrosis factor-␣ (TNF␣), interleukin-1␤ (IL-1␤), and reactive oxygen species (ROS). 2 Indeed, microglia with abnormal activity reportedly induce neuroinflammation and are implicated in the pathogenesis of Parkinson disease, Alzheimer disease, brain ischemia-reperfusion injury, trauma, epilepsy, depression, and schizophrenia (1)(2)(3)(4)(5). Therefore, understanding the mechanisms that control the microglial activity is critical, not only for comprehending the physiology of microglia but also for developing new therapeutic approaches to treating neuroinflammation and/or neurodegenerative diseases.…”