The Effects of Glutamate in the Treatment of Anxiety Disorders


Anxiety disorders are some of the most frequent psychological disorders, and the processes involved in fear conditioning seem to be the same across species, i.e. the same neural structures may be involved.

For this reason, it makes sense to study animals, because obtained knowledge from animal studies contributes to our understanding of anxiety in humans.

The treatment of anxiety disorders

Until now, the treatment of anxiety disorders has largely relied on cognitive-behavioural therapy (CBT), and indeed, CBT has shown great therapeutic effects. But how is it possible to optimize the treatment as much as possible?

A new study by Riaza Bermudo-Soriano and colleagues (2012) examined the effects of the neurotransmitter glutamate in the etiology of anxiety disorders. Perhaps the combination of CBT and glutamate regulation might be an even greater solution to the treatment of anxiety disorders.

Glutamate is a neurotransmitter that is involved in the biological mechanisms underlying stress responses. It mediates both the acquisition and extinction of fear-conditioning.

The two main brain structures that are involved in fear-conditioning is (1) the amygdala, and electric stimulation of this part of the brain results in behavioural responses similar to those of fear, and (2) the hippocampus that processes long-term memory, and the memory of a threat is accordingly stored in this part of the brain.

When one has acquired a fear-response, then is difficult to extinguish, because of the strong emotional memory that is stored in the hippocampus and the amygdala.

Fear provokes emotions, and since there is an interconnection between the amygdala and the hippocampus, the emotions originated from the amygdala will become stored in the hippocampus (see the work of Le Doux here for further details).

The medial prefrontal cortex also seems to play a part in the memory processing of fear. Glutamate may be involved in a number of psychological disorders that, in some way, are related to anxiety, such as posttraumatic stress disorder, obsessive-compulsive disorder, phobias, and panic disorder (Riaza Bermudo-Soriano et al., 2012).

Some proteins such as the polyamines may also be involved in the underlying processes of anxiety disorders, but these only have a secondary function, since they impact on glutamergic neurotransmitters.

Side-effects of glutamate?

Currently, the medical treatments of anxiety disorders are mostly based on medicine that affects GABA and serotonin neurotransmission, but these drugs do have some unfortunate side effects.

Thus, the treatment with polyamines might be an effective way to impact on glutamergic neurotransmission and facilitate the extinction of fear-responses, without posing a significant risk to one’s health.

A study by Isom and colleagues (2012) found glutamate to be potentially neurotoxic in patients treated with antipsychotic medication over a period of time.

The maximum dose of glutamate needs to be considered as well, because high amounts of glutamate may have adverse consequences on the pancreas, which is found in experiments with rats (Leshchenko et al., 2012). However, these findings seem rather inconclusive, and further research needs to examine the side effects of glutamate.

Image: Mari Z.