Cytokine Targets in the Brain: Impact on Neurotransmitters and Neurocircuits

By Andrew H. Miller, E. Haroon, Charles L Raison, J. Felger. Depression and Anxiety, 2013

794 citations recorded by the source corpus.

Increasing attention has been paid to the role of inflammation in a host of illnesses including neuropsychiatric disorders such as depression and anxiety. Activation of the inflammatory response leads to release of inflammatory cytokines and mobilization of immune cells both of which have been shown to access the brain and alter behavior. The mechanisms of the effects of inflammation on the brain have become an area of intensive study. Data indicate that cytokines and their signaling pathways including p38 mitogen‐activated protein kinase have significant effects on the metabolism of multiple neurotransmitters such as serotonin, dopamine, and glutamate through impact on their synthesis, release, and reuptake. Cytokines also activate the kynurenine pathway, which not only depletes tryptophan, the primary amino acid precursor of serotonin, but also generates neuroactive metabolites that can significantly influence the regulation of dopamine and glutamate. Through their effects on neurotransmitter systems, cytokines impact neurocircuits in the brain including the basal ganglia and anterior cingulate cortex, leading to significant changes in motor activity and motivation as well as anxiety, arousal, and alarm. In the context of environmental challenge from the microbial world, these effects of inflammatory cytokines on the brain represent an orchestrated suite of behavioral and immune responses that subserve evolutionary priorities to shunt metabolic resources away from environmental exploration to fighting infection and wound healing, while also maintaining vigilance against attack, injury, and further pathogen exposure. Chronic activation of this innate behavioral and immune response may lead to depression and anxiety disorders in vulnerable individuals.

Subfields: Behavioral Neuroscience, Biological Psychiatry, Neurology

View Paper: https://www.semanticscholar.org/paper/bc523a7513b63a195ece20f3a43529a6b24d2b36

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Citations in the corpus

Inflammation: depression fans the flames and feasts on the heat. (2015, background): “Notably, these neurotransmitter and cellular changes alter brain activity and neurocircuits underlying distress, motivation, andmotor function (16, 19).”
Early-Life Adversity and Physical and Emotional Health across the Lifespan: A Neuro-Immune Network Hypothesis (2015, background): “However, growing evidence suggests both are components of an integrated, bidirectional, network that detects threats to wellbeing and mobilizes behavioral, physiologic, and inflammatory resources for coping (11,59,60).”