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Article Review - Neuroimmune mechanisms of depression

Updated: Aug 20


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Hodes, G., Kana, V., Menard, C., Merad, M., & Russo, S. (2015). Neuroimmune

mechanisms of depression.

Nature Neuroscience, 18, 1386-1393


Article Review by Kristy Snyder Colling, Ph.D. and Robert Coben, Ph.D.


It is estimated that traditional medications for the treatment of depression

are not effective for 30-50% of patients because they don’t target the

specific underlying mechanisms, which mounting evidence suggests are

inflammatory processes. While there have been many correlational studies

linking increased inflammatory factors to diagnoses of depression and mood

disorders, some studies suggest inflammation is causal by highlighting that

children with more inflammation are more likely to develop depression and

mood disorders as adults. In contrast, those with fewer inflammatory cells

were found to be more resilient in the face of stressful events. Indeed, some

of the new drugs being eyed for future depression and mood disorder

medications work to reduce inflammation and, in so doing, decrease

depression symptoms.


So, what is the connection between depression and neural inflammation?

Animal studies have demonstrated that exposure to stressful environments

(both physical and emotional stressors) induces an immune response from

the body. Chronic stress triggers the body to release immune cells that are

inflammatory and can cross the blood-brain barrier. Once there, they affect

the circuits that control behaviors related to depression, anxiety, and mood

disorders. More specifically, they are thought to work on microglia. Microglia

have multiple functions from facilitating synaptic pruning, a process crucial

for learning new information and behaviors, to detecting neural damage and

initiating the immune response to detected damage. When microglia

functioning in the hippocampus and frontal cortex is affected, it alters

synaptic plasticity and transmission as well as neurogenesis, which can lead

to behaviors associated with depression, anxiety, and even obsessive-

compulsive disorder. Indeed, post-mortem investigations have found

increased microglia activity in both suicide victims and Alzheimer’s patients

with comorbid depression and anxiety.


The links between stress, inflammation, and depression are clear. Most

depression medications do not act on inflammation and, as a result, are often

ineffective. A better solution is to eliminate the underlying inflammation. We

at Integrated Health Coaching and as part of our Head-On program are now

offering a nutrition plan designed to reduce inflammation throughout the

body as well as enhance digestion and reduce fat and sugar intake. Contact

us to learn more about the plan and get started on your path to healthier,

happier you.

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