Effects of antidepressants on brain biochemistry

Anti-Depressants -- Brain Chemistry

The Effects Of Anti-depressants

in the human brain

the BIOLOGY of DEPRESSION:

Before commencing on the examination as to how anti-depressants affect brain chemistry, it would be best to first explore the biology of depression itself. As Prentiss Price relates, the "biological causes of clinical depression continue to be studied extensively. Great progress has been made in the understanding of brain function, the influence of neurotransmitters and hormones, and other biological processes, as well as how they may relate to the development of depression" (2004, Internet). With this in mind, it appears that hormones play a crucial role in the creation of depression and how anti-depressants affect the biochemistry of the human brain.

In recent times, numerous studies have shown that people who are depressed have abnormal amounts of certain hormones in their blood. Researchers believe that an increase or decrease in the production of specific hormones may interfere with the brain's natural chemistry which then leads to depression. With the exception of thyroid hormones, the levels of other hormones are not routinely measured when diagnosing or treating depression; thus, when a person is experiencing specific types of depression, it is advisable to check the levels of other hormones within the body. Thyroid glands, when not functioning properly, can result in the release of either too much thyroid hormone (hyperthyroidism) or too little (hypothyroidism). Either condition can lead to depression, yet it tends to be more common with hypothyroidism.

Adrenal glands also play a key role in depression, for studies have shown that those experiencing depression may have too much of the adrenal hormone cortisol in their blood. Excess cortisol can directly alter brain function and the brain's natural balance of chemical messengers known as neurotransmitters. In addition, "the hypothalamus which regulates hormone secretion, produces and releases small proteins (peptides) that act on the pituitary gland at the base of the brain" (Dunn, 1989, 67).

These peptides stimulate or inhibit the glandular release of various hormones into the bloodstream. When this occurs, the brain recognizes a potential threat and alerts the HPA axis, being the hypothalamus, pituitary and adrenal glands. Thus, many who suffer from depression exhibit an increase in the activity of the HPA axis which subsequently causes stress levels to rise and then disrupts the brain's natural chemistry which increases the risk for depression.

ANTI-DEPRESSANTS as DRUGS:

For the most part, what is currently known about the biological and chemical basis of depression came about after an effective medication had been, in some cases, discovered by accident. Thus, by attempting to figure out where in the human brain these medications are active and what they do to brain chemistry, new clues have arisen concerning the location and function of the affected mechanisms for depression.

Further research soon led to more anti-depressant medications that at first seemed to have little effect on the norepinephrine system (i.e. A group of neurotransmitters known as neuroamines). The most common anti-depressant medication used today is fluoxetine (Prozac), a powerful inhibitor of the re-uptake of the neurotransmitter serotonin. Other anti-depressants seem to affect other neurotransmitters, especially dopamine. As a result of these discoveries, the earlier amine hypothesis which stated that "an abnormally low level of norepinephrine caused depression," was greatly revised and led to a new hypothesis that depression is regulated by a complex interplay of several chemical circuits in the brain. Currently, "it is thought that the interplay of activity among all the systems is disrupted in depression" (Davis, 1984, 156).

In regard to lithium as an important anti-depressant, much effort has gone into trying to ascertain the site of lithium's activity in the brain and its effect on brain chemistry. Lithium does not appear to affect neuroamine levels like other anti-depressants and it does not interact with neuroamine receptors or the re-uptake mechanisms. Only within the last few years has the probable site of lithium action been found, namely at a different cellular level -- inside the neurons themselves instead of the synapses.

ANTI-DEPRESSANT MEDICATIONS & the BRAIN:

In most of those suffering from depression, the use of tricyclic anti-depressants is the most widely prescribed. Although other medications have been effective on the serotonin systems in the brain, the primary effect of the tricyclics seems to be an inhibition of re-uptake of the neurotransmitter norepinephrine by the neurons. Norepinephrine is usually quickly removed from the synapse and pumped back into the cell that released it in order to turn off and reset the system. By blocking the removal of norepinephrine, tricyclics appear to prolong or intensify norepinephrine's message to the post-synaptic cells.

However, the fundamental biochemical effect of antidepressants on the brain that is responsible for their benefit remains a mystery. It is thought that the change in neuroamine signaling at the synapse caused by anti-depressants "may set off a cascade of events involving second messenger systems that eventually results in the improvement of the symptoms of depression" (Enna, 1991, 187). Unfortunately, how these medications truly operate remains largely unknown.

Another group of anti-depressants is called selective serotonin re-uptake inhibitors, first introduced in 1988. Unlike the tricyclics, these new anti-depressants have little direct effect on norepinephrine in the brain; instead, they block the re-uptake of serotonin which gives this class its name, sometimes referred to as SSRIs. As with the tricyclics, the effect of serotonin in the synapse seems to occur at the receptors, and there is some evidence that "serotonin is actually the more important neurotransmitter in the treatment of depression" (Kendler, 1992, 720). The development of these new agents which help with depression but which seem to work differently from the tricyclics has provided more clues to the underlying biology of many mood disorders.

Since the early 1990's, an entirely new series of anti-depressants emerged that are neither tricyclics nor selective serotonin re-uptake inhibitors. Most of these agents do not share common features, yet they do generally effect norepinephrine, serotonin and other neurotransmitters. One of them is iproniazid, developed initially for the treatment of tuberculosis. This drug causes inactivation of an enzyme in the body that metabolizes amine compounds in the nervous system. This enzyme called monoamine oxidase "gobbles up molecules of norepinephrine, serotonin and other neurotransmitters" (Enna, 1991, 234). The inactivating effect of iproniazid on the enzyme gives this class its name -- monoamine oxidase inhibitors, or MAOIs.