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Author Notes:

Email: amill02@emory.edu

Charles L. Raison has served as a consultant for Bristol Myers Squibb, Johnson and Johnson, Pamlab LLC. and Lilly and is a speaker for Pamlab LLC. and Pfizer. Dr. Raison has also developed educational presentations for Pamlab LLC., NACCME and CME Incite.

Andrew H. Miller has served as a consultant for Abbott Laboratories, AstraZeneca, GlaxoSmithKline, Lundbeck Research USA, F. Hoffmann-La Roche Ltd., Johnson and Johnson, Schering-Plough Research Institute, and Wyeth/Pfizer Inc. and has received research support from Centocor Orthotec Services LLC., GlaxoSmithKline, and Schering-Plough Research Institute.

Ebrahim Haroon and Jennifer C. Felger have nothing to disclose.

Subjects:

Research Funding:

This work was supported in part by PHS grants from the National Institute of Mental Health (R01MH087604, R01MH083746, R01MH075102, R21 MH0771172 to AHM and PHS grants K23 MH091254 to EH and F32 MH093054 to JCF) as well as PHS Grant UL1 RR025008 from the Clinical and Translational Science Award program, National Institutes of Health, National Center for Research Resources.

Keywords:

  • Social Sciences
  • Science & Technology
  • Life Sciences & Biomedicine
  • Psychology, Clinical
  • Psychiatry
  • Psychology
  • PSYCHIATRY, SCI
  • PSYCHIATRY, SSCI
  • PSYCHOLOGY
  • PSYCHOLOGY, CLINICAL
  • inflammation
  • depression
  • anxiety
  • basal ganglia
  • dopamine
  • serotonin
  • cingulate cortex
  • TUMOR-NECROSIS-FACTOR
  • INTERFERON-ALPHA TREATMENT
  • POSTTRAUMATIC-STRESS-DISORDER
  • ANTERIOR CINGULATE ACTIVATION
  • OBSESSIVE-COMPULSIVE DISORDER
  • PRO-INFLAMMATORY CYTOKINES
  • MAJOR DEPRESSIVE DISORDER
  • BASAL GANGLIA
  • ACETYLCHOLINESTERASE ACTIVITY
  • SEROTONIN TRANSPORTERS

CYTOKINE TARGETS IN THE BRAIN: IMPACT ON NEUROTRANSMITTERS AND NEUROCIRCUITS

Tools:

Journal Title:

Depression and Anxiety

Volume:

Volume 30, Number 4

Publisher:

, Pages 297-306

Type of Work:

Article | Post-print: After Peer Review

Abstract:

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. © 2013 Wiley Periodicals, Inc.

Copyright information:

© 2013 Wiley Periodicals, Inc.

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