The role of serotonin in depression and mood regulation

Seratonin and Mood

Understanding Seratonin

Seratonin (5-hydroxytryptamine, or 5-HT) is one of the most important neurotransmitters in the human brain. Seratonin plays an important role in the central nervous system. It plays a role in mood, sleep, vomiting, sexuality, and appetite (Biver, et. al, 1997). Low levels of serotonin have been associated with depression, migraines, bipolar disorder, and anxiety (Biver, et. al, 1997). The following will explore biochemical factors that affect serotonin levels and the pharmacological treatment of these disorders.

Seratonin and Its Role in Depression

Seratonin receptors play an important role in affective disorders, such as depression and bipolar disorder. A PET can of patients with major depression revealed that altanserin uptake was significantly reduced in the right hemisphere including the posterolateral orbitofrontal cortex and the anterior insular cortex (Biver, et. al, 1997). These areas of the brain play an important role in mood regulation.

Seratonin, norepiniephrine, and dopamine are the most important neurotransmitters in the brain. These are the chemicals necessary for the transmission of signals from neuron to neuron. Seratonin is a neurotransmitter that helps one to maintain a state of emotional happiness. It has several side effects such as helping one to fall asleep, helping them to remain calm, reducing anxiety, and by relieving the symptoms of depression (Green, 2006). Dopamine is serotonins opposite. It causes people to be more talkative and excitable. Dopamine affects movement, emotional responses, and the ability to feel pleasure and pain (Green, 2006). A balance of dopamine and serotonin is necessary to maintain a healthy state of being. Too much of one or the other will produce symptoms in the abnormal range.

Low serotonin levels are involved in addictive behaviors. Certain conditions such as diabetes and alcoholism tend to make people more susceptible to depression (Green, 2006). Some foods alter the brain's behavior as well. Constant consumption of junk foods does not provide the basic building blocks to make serotonin. Therefore diet is an important part of preventing serotonin deficiency. Seratonin release is trigged by carbohydrate loading, such as with sugar (Green, 2006). Eating carbohydrates raises the level of tryptophan in the brain, which leads to serotonin synthesis and the calming effect follows. This explains why people tend to ear at times of stress. It can help to explain phenomenon such as overeating the obesity. Maintaining proper serotonin levels plays an important role in retaining a healthy mental state.

Pharmacology

The actions of serotonin in various systems are complex involving a wide array of receptors. These receptors are grouped into seven different categories. These different categories of receptors are located in different parts of the body and trigger different responses accordingly. Therefore, a different drug is needed for the specific condition that is being treated. Seratonin does so many things throughout the body that it is difficult to determine its exact role in mood. However, we do know that certain drugs and groups of drugs tend to have this affect.

Many people are familiar with serotonin and its role in human mood through the study of clinical depression. MAOIs prevent the breakdown of serotonin so that it stays in the blood stream for a longer period of time. One of the key drawbacks to MAOI therapy is that is has some adverse side effects such as hypertensive crisis, and reactions that are triggered by certain foods (Green, 2006).

Tricyclic antidepressants work in a similar fashion to MAOIs. They inhibit both the reuptake of serotonin and norepinephrine. MAOIs inhibit the reuptake of many other compounds besides serotonin. This is the reason for the range of side effects experienced by MAOIs. A new group of serotonin reuptake medications has been developed that specifically targets the reuptake of serotonin without affecting other nearby and conclusively. Antiemetics also use a SSRIs such as ondasetron, granisetron, and norepinephrine to control nausea. This is particularly useful in chemotherapy patients (Green, 2006). Florextine and Paroxetine were developed to specifically target serotonin (Schloss, 1998).

Much attention has been on the actions of Seratonin reuptake inhibitors and their contribution to the treatment of depression. These drugs work under the premise that prevention of serotonin uptake keeps more of it active in the brain and that this prevents unwanted effects such as depression and feelings of melancholy. These drugs work by filling in space in the presynaptic serotonin transporter where the serotonin would actually attach (Nickel et al., 2003). The serotonin is released, but when it arrives, there is already something in the receptor and it cannot be absorbed.

There is another drug, tianiptine, which is designed to enhance, rather than prohibit presynaptic neuronal reuptake of serotonin, which in turn decreases transmission. This is the opposite of the SSRIs that we discussed earlier. Both of these types of drugs were found to significantly improve clinical depression (Nickel et al., 2003). This study has several implications for the way SSRIs are administered. This research suggests that it is not the initial increase or decrease that is important, but that a process of normalization takes place as a result of the drug therapy. The ultimate goal, it would seem is to achieve a balance without producing an overage or underage.

Seratonin balance has also been implicated in the development of dementia in older people (McEwen et al., 1997). It is believed that adrenal glucocorticoids are responsible for atrophy and dysfunction in the hippocampus that are associated with aging and dementia (McEwen et al., 1997). The hippocampus is linked to short-term memory. Stress causes serotonin to be released. Long-term stress causes a continual flood of serotonin being released into the system. After a time of prolonged stress, the flood of serotonin can cause changes in the hippocampus and associated structures (McEwen et al., 1997). It would appear from this study that long-term stress may actually cause physical changes in the brain.

A constant flood of serotonin causes suppression of the 5-HT1A receptor. It was found that treatment with tianiptine to increase uptake of the excess serotonin helped to reduce permanent damage to the hippocampus (McEwen et al., 1997). SSRIs had no effect on reducing the damage caused by constant stress. Tianeptine also prevented stress-induced problems with maze running in rats (McEwen et al., 1997). These results suggest that treatment with agents to increase uptake of serotonin during times of prolonged stress may actually help to decrease the chances for dementia in later life. It also suggests that long-term stress may have long-term effects that can cause problems later on in life.

Seratonin syndrome is one of the dangers of taking SSRIs and MAOIs. This condition is the result of extremely high levels of serotonin and can be fatal. However, it is difficult to reach these high levels with only a single antidepressant drug. Typically serotonin syndrome is the result of patients who are on two or more types of antidepressants (Dunkley et al., 2003). True toxicity is rare, but must be a consideration when a patient begins taking more than one form of antidepressant.

In conclusion, much academic attention has been spent on the role of serotonin deficiency and its role in depression and other mood disorders. There has been increasing attention on developing SSRIs that are target-specific in an attempt to reduce unwanted side effects. However, as we have seen too much serotonin many have lasting effects on the brain and contribute to elderly dementia, or permanent damage to the hippocampus.

It appears that maintaining the proper balance of serotonin in the system is the best method for the prevention of the immediate effects of depression and the long-term effects of dementia. Diet plays an important role in the ability of the body to maintain proper serotonin levels. However, there may be times when the body simply cannot maintain the balance on its own. That is when drug therapy such as MAOIs and SSRIs come into play. These drugs are good are relieving short-term depression, but they have side effects that often make them impractical. Balancing serotonin levels is an important part of maintaining mental health. To do this one must use a combination of proper diet, plenty of sleep, exercise and the ability to ward off long-term stress.