Glutamate & Depression

Glutamate, serotonin and norepinephrin are neurotransmitters, substances that conduct signals from one nerve cell to another. Depression and other mental illnesses can arise if this signalling process goes awry. Standard drug therapies for depression have included selective serotonin reuptake inhibitors, such as fluoxetine, and drugs such as duloxetine, a serotonin and norepinephrin reuptake inhibitor. Experimental drugs that block glutamate receptors in the central nervous system or lower glutamate brain levels may represent the next generation of antidepressant medications, and offer potential advantages over current drug treatments.

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Depression is a mental illness that usually requires prolonged treatment with medication, psychological counseling, residential treatment programs or other therapies depending on the severity of the condition. Scientists think depression stems from factors that include heredity, brain levels of certain neurotransmitters, hormonal changes, personal tragedies such as the loss of a loved one, and early childhood trauma. According to, risk factors for depression include having relatives diagnosed with the condition or relatives who committed suicide, having low self esteem or excessive dependence on someone else, experiencing traumatic events in childhood, having a serious health condition such as cancer or heart disease, being poor, or abusing alcohol or illegal drugs. Symptoms include feeling sad or unhappy, loss of interest in everyday activities, excessive sleeping, changes in appetite, agitation, decreased concentration, loss of energy and feelings of worthlessness or guilt.

Role of Glutamate

Glutamate is the most abundant excitatory neurotransmitter. According to the National Institute of Mental Health, excitatory neurotransmitters are those that promote the flow of signals between nerve cells, thereby supporting the proper functioning of the cells. Scientists think glutamate may play a part in the learning process, and it may also help with memory. Mental disorders such as depression and schizophrenia stem in part from an inability of the central nervous system to effectively use glutamate.

Glutamate Receptor Blockers

Glutamate receptors are molecular structures situated on the surface of nerve cells. These structures selectively bind to glutamate, and this binding regulates glutamate-mediated nerve signals and the body's response to these signals. In an article published in the April 6, 2007, issue of "CNS and Neurological Disorders Drug Targets," researchers state that there are experimental compounds that block glutamate receptors 2, 3 or 5, and that these compounds have shown activity in animal models that predict antidepressant efficacy. Such compounds offer the possibility of treating depression through a novel mechanism of drug action.

Glutamate Brain Levels

In an article in the December 1, 2007, issue of "Biological Psychiatry," researchers report their observation of elevated postmortem levels of glutamate in the brains of patients with bipolar depression and major depression. This finding implies that elevated glutamate brain levels may be one of the causative factors in depression. The experimental drug riluzole increases glutamate uptake and curtails its release, thereby lowering glutamate brain levels. In a clinical study reported in the January 2004 issue of "The American Journal of Psychiatry," researchers found that riluzole markedly improved the major depression symptoms of all 19 study subjects.