Biology 202
1999 Final Web Reports
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Serotonin & Depression

Kathryn Ho

In the brainstem, the most primitive part of the brain, lie clusters of serotonin neurons. The nerve fiber terminals of the serotonergic neurons extend all throughout the central nervous system from the cerebral cortex to the spinal cord. This neurotransmitter is responsible for controlling fundamental physiological aspects of the body. In the central nervous system (CNS), serotonin has widespread and often profound implications, including a role in sleep, appetite, memory, learning, temperature regulation, mood, sexual behavior, cardiovascular function, muscle contraction, and endocrine regulation. Not only does this bioamine control physiological aspects of the body, but it also has an involvement in behaviors like eating, sleeping and aggression. Serotonin has been noted to produce an inhibitory effect on the nervous system that calms, soothes and generates feelings of general contentment and satiation.

Not surprisingly, serotonin is implicated in a broad range of serotonin disorders like depression, schizophrenia, and Parkinson's disease (3).. Serotonin deficiencies have been one of the factors to blame for ailments such as anorexia, bulimia, obsessive compulsive disorders, migraines, social phobias and schizophrenia. (9). (12). I am not taking a stance that serotonin has its hand in all of these different pots, but after the research that I have completed for this paper, I feel comfortable talking about serotonin in reference to depression. No one can say for certain what exactly "causes" depression. But in this paper, I hope to give further insight into serotonin's specific role as a possible predeterminant for major depression and some hopes for those suffering from this illness.

Approximately 5% of the United States' population experiences a depressive episode that requires psychopharmacological treatment; in any one year, 10-12 million Americans are affected by depression, with the condition twice as common in females than in males. It has been estimated that 15% of patients hospitalized for depression will commit suicide. These figures are incredible, so finding the root of the problem when it comes to depression is extremely important. "Alterations in serotonin metabolism may be an important factor in the etiology and treatment of depression." (7).

Although historically depression has been considered a character condition, evidence has accumulated suggesting the role of a biological substrate, namely serotonin, in subgroups of depressed patients. This accumulated evidence supports the indoleamine hypothesis of depression, which suggests that major depression results from a deficiency of available serotonin or inefficient serotonin. (16). We see that depletions of serotonin from certain regions of the brain such as the hypothalamus, amygdala, and cortical areas involved in cognition and other high processes, can have a great impact in contributing to depression. (2). We can also see that suicidal patients show prominently low levels of serotonin, which could serve to link serotonin to depression. (5).

Among the evidence supporting this hypothesis is the effectiveness of selective serotonin reuptake inhibitors (SSRIs) on depression. Serotonin's action in the synapses is terminated by reuptake of the neurotransmitter by the presynaptic cell. (4).SSRIs block the reuptake of serotonin, which leads to increased serotonergic action because there is more serotonin left in the synapse to act as a neurotransmitter.

Fluoxetine (PROZAC), a second generation SSRI anti-depressant, has been shown to effectively eliminate the symptoms of depression. In a group of smokers with a history of depression, treatment with fluoxetine ameliorated the symptoms of depression. Similarly, high dose fluoxetine treatment (60-80 mg/day) was an effective treatment in patients who were previously resistant to treatment for depression with a lower dose of fluoxetine (20 mg/day). These antidepressant effects are reversed when the levels of tryptophan, the serotonin amino acid precursor, are decreased by dietary manipulation. This reversal of antidepressant effects lends additional evidence to the indoleamine hypotheses.

Another piece of evidence in support of the indoleamine hypothesis is the reduced levels of 5-hydroxyindolacetic (5-HIAA) acid, a serotonin metabolite, in the cerebral spinal fluid of depressed patients. (17). This reduction of 5-HIAA appears to be more apparent in depressed patients who have exhibited suicidal behavior. In one study, the 5-HIAA levels were examined in thirty depressed patients with a history of suicidal behavior. Compared to the normal control subjects, the depressed patients had significantly lower 5-HIAA levels in the cerebral spinal fluid. Similarly, in another study, twelve normal healthy males with no history of depression were caused to display symptoms of depression.

This transformation was accomplished by feeding the subjects a tryptophan free amino acid mixture. This convincing study suggested a correlation between decreased levels of serotonin and depression and supports the hypothesis that low serotonin levels predispose an individual to depression. Even with using 5-HTP, serotonin's precursor, there have been studies that show that the beta endorphins, the "feel good" hormones, in a severely depressed patient, were significantly increased. This is a fairly explicit example as to how closely we can infer the role of serotonin on depression to be. (4).

Hormone responses to indirect serotonin agonists like L-tryptophan also lend evidence to the indoleamine hypothesis. Upon stimulation of the serotonin system, the hormones, prolactin and growth hormone are released. Neuroendocrine responses to the intravenous L-tryptophan were examined to compare the serotonergic function in depressed patients and healthy comparison subjects. Prolactin and growth hormone responses were decreased in depressed patients. This finding supports the evidence that serotonin function is abnormal in depression.

Motor retardation, cognitive impairment, memory lapses, and apathy are symptoms usually associated with depressions. As mentioned previously, serotonin is thought to play a role in motor activity. More specifically, it was suggested that the brain serotonin system controls the facilitation of tonic motor actions and inhibiting sensory-information processing. Serotonergic neurons functioning abnormally or not facilitating tonic motor activity explains the listless feeling and requirement of maximal energy exertion to accomplish small tasks experienced by depressed patients. Similarly, the memory associated problems may result from abnormal serotonergic activity during sensory information processing.

Based on what I have shown in this paper, I think that it is a fair inference to say that the association between abnormal serotonin systems, more specifically, serotonin deficiencies, and patients suffering from major depression is indeed significant. It is noted that 80-90% of individuals suffering from depression can be successfully treated. The treatment for patients suffering from depression may need to come in the form of antidepressant drugs and 5-HTP or Tryptophan which can indeed boost your levels of serotonin. Studies do show that "5-HTP treatment is statistically superior to placebos in treating a number of patients with endogenous depression. (4). Given that a root can be pinpointed, measures to assist those afflicted with various forms of depression can be sought out.

WWW Sources

1)The Neurobiology of Depression

1) The Neurotransmitter of the 90's

3)5-HTP Info Page


5)Research on 5-HTP


7)5-HTP L-Tryptophan

8)The Fall and Rise of Tryptophan


10)5-Hydroxy Tryptophan: Help or Hype? Can One Pill Cure Depression, Obesity and Insomnia?

11) Treating Depression

12)Brain Boon?



15)Listening to 5-HTP

16)Mood Disorders

17)Serotonin and dopamine system interactions in the reinforcing properties of psychostimulants

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This paper reflects the research and thoughts of a student at the time the paper was written for a course at Bryn Mawr College. Like other materials on Serendip, it is not intended to be "authoritative" but rather to help others further develop their own explorations. Web links were active as of the time the paper was posted but are not updated.

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