How Are Food Sensitivities and Depression Linked?

Food sensitivities or immune reactions to food have been linked to triggering several neurologic and psychiatric disorders.  This is caused by a couple of different mechanisms involving activation of the immune system.  The first is activation of a portion of the immune system called the innate immune system.  The system is the first part of the immune system to respond to challenge, and it activates systemic inflammation.  Much of how bad someone feels when they have the flu is inflammatory activation by the innate immune system.

About 1 in 10 persons will develop an innate immune response against a particular peptide in food, a problem called a foodsensitivity.  The immune system initiates an inflammatory response each time it detects the presence of that particular food peptide. 

Messengers called cytokines that activate inflammation also activate the more specialized part of the immune system called the acquired immune system.  One of its primary jobs is to produce antibodies against whatever has been perceived to be triggering the immune reaction.  Often this reaction can begin to make mistakes when it is chronically activated generating “cross-reactivity” where antibodies made against food molecules such as gluten begin to cause an attack against similarly appearing structures in the brain.

Studies have linked gluten triggered antibody reactions against brain structures in some seizures, neuropathy, migraine and cognitive impairment.  More recently the expanded knowledge of these reactions has suggested links between food reactions and two of the most common brain/mood disorders, anxiety and depression.

Typically, celiac disease is used as the model to test cross-reactivity between a food peptide and molecules in the nervous system.  Celiac disease is a cross-reactivity where antibodies against gluten begin to react with a peptide in the small intestinal lining destroying that structure.  This cross-reactivity can expand to structures in skin, glands and other areas including the nervous system.

A new study used this celiac disease model to look at nervous system involvement that may be associated with depression.  Patients with established celiac disease were examined with transcranial magnetic stimulation (TMS) which allows accurate measurement of the excitability of the brain.  All patients also completed a standardized test for depression, the Hamilton Depression Rating Scale (HDRS).  At the beginning of the trial 60% of the patients had positive depression scales.

A previous study performed by these researchers using TMS demonstrated that the celiac patients had abnormal balance between brain activation and inhibition.  The “balance” in brain response comes from the signal from one neuron to the next being “toned” by both inhibitory and excitatory interneurons.  These interneurons express neurotransmitters that turn up (excitatory) or turn down (inhibitory) the amount of signaling between neurons much like dimmer switches.

Normal information processing in the brain involves excitatory signals involved in the desired process at any moment combined with the inhibition of others that would take the desired function “off track”.

All subjects were asked to follow a gluten free diet.  Sixteen months later the TMS and the HDRS were redone.  There was actually a small reduction in the imbalance in brain activation.  In contrast, the depression scale showed active depression in only 8%, down from the original 60%.

The altered pattern of brain activation was the result of improved control of the inhibiting neurons that used the neurotransmitter GABA to produce the inhibition.  Research has indicated a high rate of cross-reactivity between gluten and casein, a peptide in dairy, antibodies with the enzyme GAD which is responsible for the production of GABA in the brain.  The antibody destruction of that enzyme appears to result in the abnormal pattern of brain activation.

This study brings up several points about the relationship between food sensitivities and depression.  The first is that once the food sensitivity is diagnosed, avoiding the triggering food improves the depression.  The second point is that the brain does not recover a normal activation pattern simply from avoiding the initial food trigger. 

The researchers discussed the failure of the brain to completely normalize its activation pattern.  The subjects were an average of 39 years of age.  Their immune reaction against gluten had been present for many years.  While the chemical stimulus to the brain which altered its activation pattern was removed, the abnormal brain pattern had likely become “learned”.

All learning comes through repeated stimuli to the brain resulting in neurons developing preferred connections and activation patterns.  We now know that when this has occurred with an abnormal activation pattern such as stress, the brain eventually “learns” that preferred pattern.  At this point in time techniques such as neurofeedback which is EEG guided brain training must be used to re-train the brain back into a more normal pattern.

For many the best outcome with depression will result from finding the original trigger such as a food sensitivity but then restoring normal brain activation patterns with neurofeedback.