Depression and Inflammation Interactions

Inflammation and Depression - Punishment SensitivityThere has been a lot of interest in the last year in the idea that information or activation of the body’s immune system, might be a cause and/or consequence of depression.  One theory argues that depression might be an inflammatory disorder, more than a disorder of altered neurotransmitter levels.

Certainly there’s a fair amount of information that some people with depression have increased markers of inflammation, and there’s even some evidence to suggest that elevated inflammation markers in the blood can predict who will and will not respond to a given antidepressant, but how exactly does inflammation or immune system activation, affect the brain and how could it lead to depression?

This past week I came across a review of an article that suggests a mechanism whereby inflammation can affect mood.  The article was reviewed in the New England Journal of Medicine’s Psychiatry Updates Series.

In a relatively small study, twenty-four subjects without depression received an injection of typhoid vaccine, a vaccine that reliably induces a short term inflammatory response (activating the immune system in the body) and a matched group received an injection of placebo.  The investigators then looked at decision making in a situation where there were potential rewards and potential punishments depending on choices made.

They were able to show a significant effect of the typhoid induced inflammation on people’s willingness to choose potential rewards in a situation where there might also be a risk.  In other words, those who had higher levels of inflammation were more focused on punishment than reward, a shifting cognition that certainly fits with the changes that take place in depression.

This is a small study but it could suggest a way of linking depression and stress, which Inflammation and Punishment Sensitivityinduces significant changes in immune functioning, and alterations in neurotransmitter systems.  Perhaps all of these reflect the body’s integrated assessment of threat at various levels: psychological, immunological, etc., and depending on that sense of the dangerousness of the environment, the body either activates more reward seeking behavior (when there’s not much danger) or goes into a state of avoiding punishment and heightened alertness for infection and threats of various kinds.

Readers of this blog may recall a recent interview with Dr. Sheri Johnson at the University of California, Berkeley. She summarized a great deal of information suggesting that heightened focus on reward and a relative neglect of awareness of potential punishment may be a key phenomenon that explains or at least contributes to the development of mania. Perhaps the reciprocal activation of parts of the brain focused on punishment or reward may be linked to the development of bipolar mood shifts…

An interesting idea to keep an eye on.


Harrison NA et al. A neuro-computational account of how inflammation enhances sensitivity to punishments versus rewards. Biol Psychiatry 2015 Aug 1; [e-pub]. (