[Please read the disclaimer for this journal before jumping in - I am a student and do not diagnose or treat symptoms. This paper is for an introductory psychopathology class. Please be kind and do not steal my work (though I encourage those interested to look up the references)]
Low Serotonin Theories
Introduction
Modern psychiatry understands an element of depression to be a deficit in the neurotransmitter serotonin. As society, medicine, and therapy advance, there seems to be a shift from simply treating symptoms. Instead, society and the scientific community seek to understand the underlying causes of their illness, which begs the question: if a person is depressed because of low serotonin, what is causing it to be low to begin with? There are several theories on the subject, and it is possible that most of them are correct – at least for some people. As the search for causes presses on, there is increased awareness that a one-size-fits-all model of cause and treatment is, at best, incomplete. Still, the theories presented are shaping the worlds understanding of depression and other symptoms that arise from low serotonin. The following is only a handful out of a potentially infinite number of theories.
The Genetic Theory
There is no doubt that genes play a role in who we are. According to Comer, family pedigree and twin studies have revealed that genetically related individuals have higher rates of depression than the general population, suggesting a fairly strong genetic component. In both family pedigree studies and DZ twin studies, rates of depression were at about twenty percent, versus less than ten percent for the general population (Comer, 2008). In identical twin studies, the rate was much more significant – MZ twins showed that 46 percent of the time, if one twin suffered depression, so did the other (Comer, 2008).
It is suggested that the gene SLC6A4 (alternatively referred to at 5-HTT or Serotonin Transporter) plays a role in uptake rates of serotonin. According to the NCBI website on the human genome project:
This gene encodes an integral membrane protein that transports the neurotransmitter serotonin from synaptic spaces into presynaptic neurons. … A repeat length polymorphism in the promoter of this gene has been shown to affect the rate of serotonin uptake and may play a role in sudden infant death syndrome, aggressive behavior in Alzheimer disease patients, and depression-susceptibility in people experiencing emotional trauma (SlC6A4 solute carrier family 6, 2010).
That is to say, mutation of this gene doesn’t necessarily cause low levels of serotonin but mutations in it may cause alterations in the rate of synapse and reuptake, which in turn, may affect the emotional well being and health of the individual.
The Amino Acid Theory
According to Natural Doctors Michael Murray and Joseph Pizzorno, tryptophan, an amino acid found in the human diet, is essential for healthy levels of serotonin (1998). In experimental studies where subjects are fed diets devoid of tryptophan, it is noted that depression is a common result or effect among test subjects. Still, this is not the entire story. According to Murray and Pizzorno (1998):
Supplementation with tryptophan in depressed individuals has produced mixed results in the published clinical trials. In only two out of eight studies that compared tryptophan to a placebo was tryptophan shown to be more effective than the placebo. … A number of factors, such as hormones (estrogen and cortisol) and tryptophan itself, stimulate the activity of tryptophan oxygenase, which results in tryptophan being converted to kynurenine and less tryptophan being delivered to the brain (p. 380).
Once tryptophan is consumed, an enzyme in the body converts tryptophan into 5-HTP (5-Hydroxytryptophan), a precursor to serotonin and melatonin (perhaps this also explains insomnia in some depressed patients). It is also suggested that some people lack the enzyme that converts tryptophan into 5-HTP. According to Murray and Pizzorno (1998):
Unlike tryptophan, 5-HTP cannot be converted into kynurenine … As a result, while only three percent of an oral dose of tryptophan is converted into serotonin, over 70 percent of an oral dose of 5-HTP is converted to serotonin. … Numerous double blind studies have shown that 5-HTP has equal effectiveness compared to drugs like Prozac, Paxil, and Zoloft (the selective serotonin reuptake inhibitors, SSRIs) and tricyclic antidepressant drugs… (p. 380, 390-393, 686-687).
In addition, the decreased conversion of tryptophan into 5-HTP has been linked to obesity, lack of satiety, (Murray et al., 1998) and difficulties with sleep cycles (Murray et al., 1998), all of which are reported to be symptoms linked with depression.
The Hormonal Theory
There are two hormones suspected to affect serotonin levels: cortisol and estrogen. Cortisol is a hormone released by the adrenal glands in times of stress. Comer (2008) writes:
People with unipolar depression have been found to have abnormal levels of cortisol; one of the hormones released by the adrenal glands during times of stress … This relationship is not all that surprising, given that stressful events often seem to trigger depression (p. 193).
Murray and Pizzorno (1998) argue that perhaps it is not necessarily the stressful event that triggers depression, but the hormone cortisol that is released by the adrenal glands in times of stress:
When the adrenal gland releases increased amounts of natural cortisol, its effects on brain mirror the side effects of synthetic cortisones such as prednisone: depression, mania, nervousness, insomnia, and, at high levels, schizophrenia. The effects of cortisol on mood are related to its activation of tryptophan oxygenase … results in shunting of tryptophan to the kyneurenine pathway at the expense of serotonin and melatonin synthesis (p. 383).
As previously discussed, tryptophan is a part of the human diet, essential in the production of serotonin. If the body converts tryptophan into kyneurenine instead of 5-HTP, serotonin cannot be produced.
Another hormone linked to serotonin production is estrogen. According to Sandhya Pruthi, M.D. on the Mayo Clinic website, PMS (premenstrual syndrome) and PMDD (premenstrual dysphoric disorder) are characterized by bouts of depression or sadness (Premenstrual Syndrome, June 21, 2008). According to Comer (2008):
…Other biological researchers are beginning to suspect that unipolar depression is tied more closely to what happens between neurons …. They believe that abnormal activity by key neurotransmitters or hormones ultimately leads to deficiencies of important proteins and other chemicals within neurons – deficiencies that impair the health of the neurons and lead, in turn, to depression (p. 193).
Murray and Pizzorno (1998) take note of a link between female sex hormones and depression:
It is interesting to note that the majority of the over twelve million patients who take Prozac are women between the ages of twenty-five and fifty – the same population that has a high frequency of PMS (p. 737).
Murray and Pizzorno (1998) expand on these ideas by discussing the effects of abnormal estrogen levels on neurotransmitters. They suggest that estrogen excess impairs synthesis of neurotransmitters, including serotonin (732). Increased levels of estrogen can prevent the amino acid tryptophan from reaching the brain in the form of 5-HTP.
Conclusion
These are but a few of the theories for low serotonin levels seen in many patients suffering from depression. Each theory seems that it can build upon another – although the discussed gene (one of potentially several that plays a role in serotonin levels) does not appear to be inherently related to either the amino acid or hormonal theories, it is likely that genes influence enzyme and hormonal activity, which in turn, affects serotonin production. Furthermore, the amino acid theory is enhanced by the hormonal theory – if the proper amino acids are not properly converted and able to reach the brain, hormones might be a potential cause.
One thing is for certain – the search for causes will be an extensive one. At each new level of understanding, we have to ask, “What is causing the malfunction?” For the theories given, we could arguably state, “low serotonin levels in case A are caused by a lack of tryptophan from reaching the brain, which is caused by increased cortisol secretion … which is caused by these genetic factors.” It seems that with theories for low serotonin, each answer brings about a new round of questions – this is the beauty and frustration that is science.
References
Comer, R. J. (2008). Fundamentals of Abnormal Psychology. New York, NY: Worth Publishers.
Murray, M. T., N.D., & Pizzorno, J. E., N.D. (1998). Depression. In Encyclopedia of Natural Medicine (Vol. 2, Rev., pp. 380-393, 686-687, 732-737). Roseville, CA: Prima Publishing.
SLC6A4 Solute Carrier Family 6. (2010). Retrieved April 04, 2010 from National Center for Biotechnology Information: http://www.ncbi.nlm.nih.gov/gene/6532?ordinalpos=1&itool=entrezsystem2.pentrez.gene.gene_resultspanel.gene_rvdocsum.
Pruthi, S., M.D. (2008). Premenstrual Syndrome (PMS). Retrieved April 05, 2010 from Mayo Clinic Online: http://www.mayoclinic.com/health/pmdd/an01372.
