Inflammation and depression but where does the inflammation come from?Halaris, AngelosCurrent Opinion in Psychiatry: September 2019 - Volume 32 - Issue 5 - p 422–428 doi: 10.1097/YCO.0000000000000531 PSYCHIATRY, MEDICINE AND THE BEHAVIOURAL SCIENCES: Edited by Mohan Isaac and Igor Filipcic Buy Abstract Author InformationAuthors Article MetricsMetrics Purpose of review Up until the latter part of the previous century, the monoamine theory guided our understanding of psychiatric disorders, notably depressive illness in its various phenotypic manifestations. The purpose of this review is to provide an overview of newer theories that allow a deeper understanding of brain dysfunction and neuropsychiatric disease entities such as depressive illness. One such key theory is the theory of inflammation as a result of stress-induced immune system activation. Recent findings Stress activates the hypothalamic–pituitary–adrenal axis and the sympathetic branch of the autonomic nervous system [sympathetic branch (SNS)] with a concomitant reduction in vagal tone. This homeostatic imbalance makes a simultaneous dual contribution to the resulting proinflammatory state of depression. SNS stimulation results in upregulation of proinflammatory signaling, whereas diminution in parasympathetic tone affects the body's immune response. The resulting proinflammatory status has been closely associated with multiple organ dysfunction and comorbid conditions. Summary The advent of innovative theories about the pathophysiology of psychiatric disorders has ushered in a new era on the basis of the role of the immune system and inflammation in mediating depression in its multifaceted manifestations. Extensive studies have confirmed the proinflammatory status in depression and causal relationships with neurotransmitter dysregulation. Equally importantly the role the autonomic nervous system plays in this complex and multifactorial interplay of body systems is being increasingly elucidated. Department of Psychiatry and Behavioral Neuroscience, Loyola University Chicago Stritch School of Medicine & Loyola University Medical Center, Maywood, Illinois, USA Correspondence to Angelos Halaris, MD, Ph.D., Department of Psychiatry and Behavioral Neuroscience, Loyola University Medical Center, Bldg. 54, 2160 South First Avenue, Maywood, IL 60153, USA. Tel: +1 708 216 3752; e-mail: firstname.lastname@example.org Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.