Therapeutic Implications of Brain–Immune Interactions: Treatment in Translation
Open accessAbstract
A wealth of data has been amassed that details a complex, yet accessible, series of pathways by which the immune system, notably inflammation, can influence the brain and behavior. These data have opened the window to a diverse array of novel targets whose potential efficacy is tied to specific neurotransmitters and neurocircuits as well as specific behaviors. What is clear is that the impact of inflammation on the brain cuts across psychiatric disorders and engages dopaminergic and glutamatergic pathways that regulate motivation and motor activity as well as the sensitivity to threat. Given the ability to identify patient populations with increased inflammation, the precision of interventions can be further tuned, in conjunction with the ability to establish target engagement in the brain through the use of multiple neuroimaging strategies. After a brief overview of the mechanisms by which inflammation affects the brain and behavior, this review examines the extant literature on the efficacy of anti-inflammatory treatments, while forging guidelines for future intelligent clinical trial design. An examination of the most promising therapeutic strategies is also provided, along with some of the most exciting clinical trials that are currently being planned or underway.
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The observed effects of standard antidepressants (an overall decrease in predominantly inflammatory cytokines and chemokines) may not be the main mechanism contributing to the therapeutic benefits of these drugs.
“Therefore, it is possible that the observed effects of standard antidepressants observed herein (i.e., an overall decrease in predominantly inflammatory cytokines and chemokines) may not be the main mechanism contributing to the therapeutic benefits of these drugs [39].”
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- Authors
- Miller, A. H., Haroon, E., & Felger, J. C.
- Affiliations
- Emory University (US)
- Corresponding author
- Miller, Andrew H
- Venue
- Neuropsychopharmacology
- Published
- 2016-08-24
- Volume
- 42
- Issue
- 1
- Pages
- 334-359
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC5143492
- OpenAlex
- W2507921187
- Cited by
- 152
- References
- 241
- Citations by year
- 2026: 13 · 2025: 16 · 2024: 8 · 2023: 10 · 2022: 25 · 2021: 19 · 2020: 18 · 2019: 10 · 2018: 20 · 2017: 10 · 2016: 3
- FWCI
- 0.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (UL1TR000454, UL1TR002378)
- National Institute of Mental Health (R21MH077172, R01MH083746, R01MH112076, R21MH106904, R03MH100273, R01MH109637, R01MH107033, R01MH087604, R21MH105897)
- National Cancer Institute (P30CA138292)
- National Center for Research Resources (UL1RR025008)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- neuroimmune interactions, neuroinflammation, anti-inflammatory therapy, mental illness, dopaminergic pathways, glutamatergic pathways, motivation, threat sensitivity, neuroimaging, clinical trial design, translational research
- MeSH terms
- Animals, Mental Disorders, Brain, Humans, Inflammation, Neurotransmitter Agents
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