Inflammation in the pathogenesis of depression: a disorder of neuroimmune origin

Abstract

Pathophysiological mechanisms of major depression, which centre largely around adaptive changes in neuronal transmission and plasticity, neurogenesis, circuit and regional connectivity. The immune and endocrine systems are commonly implicated in driving these changes. An intricate interaction of stress hormones, innate immune cells and the actions of soluble mediators of immunity within the nervous system are described as associating with the symptoms of depression. Bridging endocrine and immune processes to neurotransmission and signalling within key cortical and limbic brain circuits is critical to understanding depression as a disorder of neuroimmune origins. Emergent areas of research include a growing recognition of the adaptive immune system, advances in neuroimaging techniques and mechanistic insights gained from transgenic animals. Elucidation of glial-neuronal interactions is providing additional avenues into promising areas of research, the development of clinically relevant disease models and the discovery of novel therapies. This narrative review focuses on molecular and cellular mechanisms that are influenced by inflammation and stress. The aim of this review is to provide an overview of our current understanding of depression as a disorder of neuroimmune origin, focusing on neuroendocrine and neuroimmune dysregulation in depression pathophysiology. Advances in current practice lie in pursuit of relevant biomarkers, as the potential of biomarker signatures to improve clinical outcomes is yet to be fully realised. Further investigations to expand biomarker panels including integration with neuroimaging, utilising individual symptoms to stratify patients into more homogenous subpopulations and targeting the immune system for new treatment approaches will help to address current unmet clinical need.

Saffron extract interferes with lipopolysaccharide-induced brain activation of the kynurenine pathway and impairment of monoamine neurotransmission in mice

“…A limitation of the current work is that it does not allow to conclude on the inflammation-induced symptoms more likely to be ameliorated by nutritional interventions with saffron or on which brain area might be most important in this regard. However, this was not the question addressed here and it would not necessarily be relevant anyway, depression being a highly multidimensional disorder that involves complex neuronal networks broadly distributed in the brain ( 94 , 95 ). Instead, this study focused on the main neurobiological systems whose alteration in inflammatory conditions can contribute to the development of a large panel of behavioral symptoms.…”

How inflammation influences psychiatric disease

“…As previously described, peripheral proinflammatory cytokines stimulate the brain and generate a neuroinflammatory response caused by the activation of neurons, microglia, and astrocytes[ 46 ]. Proinflammatory cytokines induce changes in the metabolism of tryptophan, a precursor of serotonin in both the periphery and the brain, thereby increasing inflammation and decreasing serotonin production[ 47 ].…”

Understanding the Biological Relationship between Migraine and Depression

“…With regard to depression, the accumulated preclinical and clinical evidence clearly indicates that there is systemic immune activation, which is reflected in significant changes in the levels of inflammatory markers and in the type and number of immune cells [432][433][434]. In fact, increased levels of peripheral proinflammatory cytokines, mainly IL-1β, IL-6, and TNFα, have been described in depressed patients [435,436].…”