Depression and Inflammation

Peter ForsterBasic Science, Major Depression, Psychobiology

Is depression one of a series of illnesses caused by inflammation?

There has been a lot of interest in the last year in the idea that inflammation (activation of the body’s immune system) might be a cause as well as a consequence of depression.

One theory suggests that depression might be an inflammatory disorder, rather than a disorder of altered neurotransmitter levels.

Certainly there is evidence that some people with depression have increased levels in their blood of a number of 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?

One of the nice things about the neurotransmitter hypothesis, in addition to evidence suggesting that there are alterations in the serotonin systems in the brains of some people with depression, is a wealth of evidence that shows how neurotransmitters influence mood.

Recently I came across a review of a study that suggests how inflammation may affect mood.  The article was reviewed in the New England Journal of Medicine’s Psychiatry Journal Watch.

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.  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 of punishment.

Those who had higher levels of inflammation were more focused on punishment than reward, a shift in cognition that mirrors the changes that take place in depression.

This is a small study but it could suggest a way of linking depression and stress, which induces 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.  An interesting idea to keep an eye on.

Here is Steven Dubovsky’s summary of the article –

Inflammation appears to increase relative sensitivity to punishment over reward, leading to a tendency to emphasize negative over positive expectations. This shift seems to occur via changes in activity in the ventral striatum and insula, perhaps mediated by altered dopamine neurotransmission. Because iatrogenic (e.g., with interferon) or spontaneous inflammation is regularly associated with depression and with feeling sick and withdrawn, treatments targeting the inflammatory response or its actions in decision-making centers might help to moderate the negative expectations seen in both depression and entrenched illness behavior.


A Link Between Depressive Cognition and Inflammation. Steven Dubovsky, MD Reviewing Harrison NA et al., Biol Psychiatry 2015 Aug 1;

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

For More Information

Escitalopram Reduces Inflammation in Depression

Simple Test May Predict Which Antidepressant Will Work

Methylfolate and Depression

Exercise and Stress – How Exercise Prevents Depression