Monoamine Theory of Depression

The monoamine theory of depression holds that clinical depression results from low levels in the brain of serotonin, norepinephrine or both. The theory holds that increasing the levels of these brain chemicals -- known as neurotransmitters -- could alleviate or completely reverse depression.

History

• In the late 1950s, two classes of medications were discovered to be beneficial in treating depression: monoamine oxidase inhibitors and tricyclic antidepressants. By the late 1960s, research had determined that both classes increased brain levels of norepinephrine and serotonin. At that time, it was also found that reserpine, a drug that depletes neurotransmitters, could cause depression in about 15% of individuals. These findings paved the way for the monoamine theory of depression, which posited that clinical depression is the result of a monoamine deficiency.

Seratonin and Norepinephrine

• Serotonin performs a variety of functions in the brain. High levels of serotonin increase tolerance to pain, decrease cravings for food, improve mood, and enhance sleep. Low levels result in increased sensitivity to pain, food cravings, depression, insomnia, aggressive behavior and poor-body temperature regulation. Seratonin is made in the brain from the amino acid tryptophan, along with folic acid and vitamins B6 and B12.

  Norepinephrine is manufactured from tyrosine, an amino acid, as well as folic acid, magnesium, and vitamin B12. A drop in norepinephrine levels produces feelings of depression and irritability. Consuming more tyrosine raises norepinephrine levels and improves mood, increases alertness, alleviates stress and boosts mental functioning.

Research Findings

• Initial studies of monoamine concentrations in patients with mental disorders yielded confusing results. Some studies indicated that levels of monoamine metabolites are decreased in the cerebrospinal fluid of depressed individuals, but others found no difference -- or even increased levels Furthermore, most research subjects who are given drugs that deplete neurotransmitters do not become depressed. Also, even though antidepressant drugs raise monoamine levels in all patients, they provide effective relief for only about 60% of them. Finally, synaptic monoamine levels rise rapidly with the inititiation of antidepressant therapy, yet clinical response does not occur for several weeks. Taken together, these findings suggest that the clinical response to antidepressants is not caused by increases in monoamine, but rather by later onset adaptations in that occur in response to the shifts in monoamine levels.

Cellular Malfunction

• The monoamine theory states that several cellular abnormalities may develop at the level of the synapse, the junction between brain cells across which signals are sent.

  The first of these is excessive reuptake, which results in significant amounts of released neurotransmitters being reabsorbed. Another involves decreased release of neurotransmitters into the synapse. A third occurs when the enzyme monoamine oxidase becomes too active and excessively degrades neurotransmitters, which results in depression. A fourth way that cells can malfunction is due to a disruption in the synthesis of neuroprotective proteins. The fifth and final type of cellular dysfunction may be traced to abnormalities in receptors.

Considerations

• The monoamine theory of depression is an overly simplified notion, but it has been very valuable in focusing attention on the monoamine neurotransmitter systems. This, in turn, has led to a much better understanding of the physiological function of neurotransmitters and the various mechanisms by which all known antidepressants act to increase neurotransmission.