Both norepinephrine (NE) and serotonin (5-HT) play a role in depression and are involved in antidepressive pharmaceutical treatments. Studies show that NE and 5-HT interactions are involved but, neither is the “final common pathway” of depression. Neither NE nor 5-HT depletion causes depression in normal patients or in unmediated symptomatic patients with major depression. On the other hand, depression is relieved by NE in some people and by 5-HT in others. The factors that cause depression seem to be quite complex and the mechanism of depression is not known. A deficiency of NE or 5-HT may not be the sole cause of depression.
Brain levels of 5-HT are dependent on blood levels of tryptophan, whch is an essential amino acid and must be ingested. Depletion of tryptophan in the diet will deplete brain levels of 5-HT. This study has been done on humans using a tryptophan free amino acid drink, resulted in an 80 to 90% depletion of tryptophan within 5 hours. Tryptophan depletion studies do not cause clinical depression although some untreated depressed patients show low levels of tryptophan.
The presence of 5-HT is necessary for antidepressant drugs that enhance 5-HT and the presence of NE is necessary for antidepressant drugs that enhance NE. Both the 5-Ht and NE systems seem to be important. The authors suggest that future research should include studying the areas of the brain that are sensitive to NE and 5-HT, such as the basal ganglia, frontal cortex and hippocampus/amygdala.
The production of NE and dopamine are dependent on the conversion of tyrosine to l-dopa. This fact can be used in studies of NE and dopamine depletion that can be produced by blocking the enzyme that converts tyrosine to l-dopa. This causes sedation but not depression.
CONCLUSION: The basis of depression is not clear and NE and 5-HT systems are important. Depression is not the result of simple insufficiency of NE or 5-HT. The authors suggest further study of the specific areas of the brain that are sensitive to norepinephrine and serotonin. These areas would include the amygdala, frontal cortex, basal ganglia, and hippocampus. This might be more productive than studies of norepinephrine and serotonin in defining the cause of depression.