Inflammation and depression but where does the inflammation come from? Author: Halaris A1 Affiliation: <sup>1</sup>Department of Psychiatry and Behavioral Neuroscience, Loyola University Chicago Stritch School of Medicine &amp; Loyola University Medical Center, Maywood, Illinois, USA. Conference/Journal: Curr Opin Psychiatry. Date published: 2019 Jun 11 Other: Special Notes: doi: 10.1097/YCO.0000000000000531. [Epub ahead of print] , Word Count: 226 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. PMID: 31192815 DOI: 10.1097/YCO.0000000000000531