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Modes of Therapy

ACTSCI-E51ABT

Neurotransmitters like Serotonin and Dopamine play a role in the modulation of mood. A detailed investigation of the pattern of this association has assumed great significance with studies indicating an association between these chemicals and suicidal tendency.

A study was undertaken to investigate the details of the roles of neurotransmitters in mood disturbances, specifically depression. People were examined to find if they were suffering from depression, and samples of their cerebrospinal fluids were taken to measure the levels of neurotransmitters. Cerebrospinal fluid (CSF) is a protective nourishing fluid that circulates around the brain and spinal cord of the central nervous system.

1,000 people were examined and their CSF samples analyzed to determine the levels of Serotonin. The results are tabulated below.

Table 1

Depression present Depression not present
Serotonin level low in CSF 90 90
Serotonin level normal in CSF 10 810

CSF samples of the same 1000 people were analyzed to determine the levels of Dopamine. The results are given in table 7.2.

Table 2

Depression present Depression not present
Dopamine level low in CSF 70 150
Dopamine level normal in CSF 30 750

To define the exact roles of the abnormal levels of various neurotransmitters in causation of depression, experiments were conducted on mice that showed signs and symptoms of depression.

Experiment 1

100 mice that showed signs and symptoms of depression were given exogenous serotonin. 90 of these showed an improvement.

Experiment 2

Serotonin is metabolized in the body mainly by liver. An enzyme monoamine oxidase first converts it into an aldehyde; and then aldehyde dehydrogenase converts this aldehyde to 5-hydroxyindoleacetic acid (5-HIAA).

The mice that did not respond to exogenous Serotonin in experiment 1 were administered 5-HIAA. Five of these showed an improvement.

Experiment 3

The 90 mice that showed improvements in the first experiment were not administered any further doses of Serotonin. Starting from the first animal at 7 days, all of them developed signs and symptoms of depression by the 30th day. On the 31st day, they were administered exogenous 5-HIAA. All of them showed an improvement.

A group of people suffering from depression were administered Serotonin but they did not show any improvement. 5-HIAA was produced from Serotonin in vitro and administered to them. 50% of the patients showed an improvement. The CSF samples of these 50% were analyzed and half of the people had normal levels of Serotonin.

Which of these modes of therapy is likely to benefit such patients who have normal Serotonin levels but respond to exogenous 5-HIAA?

A

Exogenous administration of an allosteric inhibitor of monoamine oxidase.

B

Exogenous administration of an allosteric inhibitor of aldehyde dehydrogenase.

C

Trials of exogenous monoamine oxidase and aldehyde dehydrogenase; and continuation of the enzyme(s) to which the subject responds.

D

Administration of Serotonin along with gene therapy to introduce genes coding for monoamine oxidase and aldehyde dehydrogenase.