May 2, 2009
Neurobiology and Behavior
Depression – What exactly is it? Why does one medication not work for everyone, if it is the same thing in everyone? What do antidepressants do?
The perception that many people have of depression is vague and limited to hearsay that is passed along. When the topic of depression was brought up in class I realized just how limited my understanding of depression is. The only ideas I had on the topic was that it was a mental disorder and that it can be treated by antidepressants. Since that is the basis of what I know I decided to expound and widen my search on the topic.
Depression affects more than 15 million people a year in the United States alone, which is a much higher number than I would have anticipated; it transfers to about 6 percent of the population (Holden). This is an incredibly large number, giving it much more credibility as a serious disorder than people probably give it credit for. That is six people out of every hundred people. Our college, which has about 1,200 students, should have about 72 students suffering from depression; if we are following the nation’s averages. Not only is depression incredibly common it is also devastating in its severity. In the 30,000 suicides that occur each year in the United States, depression is almost always a factor (Holden). This calls to question many doubts that depression is a real problem, giving the facts and numbers to back up just how problematic it is in our country alone. Depression also ranks in the top five leading causes of diseases and disability on a worldwide scale (Capsi). Depression is not just a sad time in a person’s life; as we have just explored, it goes much farther than that. A quote that sums up that argument nicely is “And since the 1950s, with the advent of the first generation of antidepressants, it has been apparent that depression is a biological disorder.” (Sapolsky)
During my research I read many theories on the physical aspects on why depression occurs. One was that individuals with at least one copy of the short allele of the 5-HTT promoter had more symptoms of depression, diagnosed depression and cases of suicide when faced with stressful events in life, compared to individuals who possessed only the long allele (Capsi). That means there is research supporting the fact that certain people have a higher probability of not dealing with these events easily based on their genetic makeup. Some theories predict that the sensitivity to stressful events depends on their genetic makeup making them more predisposed to depression. Some events that may bring about the onset of depression are threat, loss, humiliation and defeat as stated by Capsi. So individuals who are diagnosed as depressed are not weak or unable to cope with life, they were simply handed a bad hand of cards and are living life with what they were given. They are unable to change their genetics, backgrounds and predispositions to the situations they are put in during their lifespan.
Another theory on why depression occurs is that GABA and glutamate neurotransmitter systems are elevated in the cerebral cortex of individuals diagnosed with depression (Choudary). That means that if there are more neurotransmitters in the cerebral cortex then more of those substances are getting in. Just because there is a difference in the cerebral cortex of someone with depression does not mean that that is solely the cause of depression, just another clue to figuring out what exactly is going on to make this happen.
Not only is there evidence for depression being caused by physical changes but also physical effects of prolonged depression. There are some experiments that show that prolonged and major depression is associated with atrophy in the central nervous system, within the hippocampus (Sapolsky). The longer the depression then the more severe the atrophy and reduction to the hippocampus appeared (Sheline, Sapolsky), though the atrophy only appears demonstrable after severe depression lasts a scale of years (Sapolsky). The loss of those preexisting neurons in the hippocampus is called neurotoxicity. Excess cortisol is the reason for several physical effects as well which include retraction of dendritic processes, inhibition of neurogenisis, and neurotoxicity (Sapolsky).
There are also studies where major depression has been associated with low bone mass and more frequent osteoporotic fractures. The bone fragility is said to be connected to the much higher levels of norepinephrine that can be blocked. This is signifying that the sympathetic nervous system mediates the skeletal effects of stress induced depression. This is not an insignificant difference but one of an unexpectedly high number; 6 to 15% lower bone mineral density in depressed patients. (Yirmiya) These are just a few responses that the body has to depression, but they are significant and detrimental enough to raise a few concerns.
Depression is not equal in who it affects, making women twice as likely to suffer from major depression as men. Women who are depressed also have longer episodes of depression and are less likely to have a spontaneous remission of that depression. Women generally see the first onset of depression during their childbearing years opposed to men who see it later in life. I am not sure if women are depressed because they are in their childbearing years or if there is some sort of correlation, but it does seem significant enough compared to the onset with men. Another astonishing figure is that about 10% of pregnant women in the United States meet the criteria for major depression. While the other averages and numbers were on a global scale this is specific to the United States, and it is not something to be dismissed. That is one out of every ten pregnant women, which just brings to mind what effects are there on the fetus. At such a high number with incredible amount of risks, it is possible that these unborn children are being harmed in some way that we are not yet sure of.
Most antidepressants act on an individual or both major neurotransmitter systems which are the serotonergic system, using serotonin as a transmitter, and the noradrenergic system, using norepinephrine as a transmitter. These antidepressants block the reuptake the neurotransmitters making a larger quantity available to stimulate post-synaptic receptors. This regulates many functions including mood, arousal, appetite and sleep. (Holden) That is how they act on the body, which is not equivalent of saying that it is going to have the exact same effect on everyone.
Treating depression using antidepressants is not as surefire a way of coping with depression as everyone seems to think. Antidepressants may take as long as 6 weeks to kick in and only work for about 70% of sufferers. They also have very unpredictable side effects on a case-to-case basis. (Holden) They are not guaranteed because offering that guarantee would be impossible. There are too many variations among human beings for one drug to work on everyone.
Throughout this research I have seen that depression cannot be easily defined by what, why and when questions but need to be delved into on a more complex level. Many misconceptions that I was not aware that I held were brought to light and thoroughly dismissed when presented with such astounding details and explorations of depression. I have seen that it is not merely a term to be bandied with friends when you are having a bad day, but a serious disease that many people struggle with on a daily basis.
Capsi, Avshalom, Karen Sugden, Terrie E. Moffitt, Alan Taylor, Ian W. Craig, HonaLee Harrington, Joseph McClay, Jonathan Mill, Judy Martin, Antony Braithwaite, and Richie Puolton. "Influence of Life Stress on Depression: Moderation by a Polymorphism in the 5-HTT Gene." Science Vol. 301, No. 5631. 18 July 2003. Pages 386-389. 1 May 2009. <http://www.jstor.org/stable/3834746 >.
Choudary, P.V., M. Molnar, S.J. Evans, H. Tomita, J.Z. Li, M.P. Vawter, R.M. Myers, W.E. Bunney Jr., H. Akil, S.J. Watson, and E.G. Jones. "Altered Cortical Glutamatergic and GABAergic Signal Transmission with Glial Involvement in Depression." Proceedings of the National Academy of Sciences of the United States of America Vol. 102, No. 43. 25 Oct 2005. Pages 15653-15658. 1 May 2009. <http://www.jstor.org/stable/4143490 >.
Holden, Constance. "Depression: The News Isn't Depressing." Science Vol. 254, No. 5037. 06 Dec 1991. Pages 1450-1452. 6 May 2009. <http://www.jstor.org/stable/2879418 >.
Sapolsky, Robert M. . "Depression, Antidepressants, and the Shrinking Hippocampus." Proceedings of the National Academy of Sciences of the United States of America Vol. 98, No. 22. 23 Oct 1991. Pages 12320-12322. 6 May 2009. <http://www.jstor.org/stable/3056897 >.
Sheline, Yvette I., Po W. Wang, Mokhtar H. Gado, John G. Csernansky, Michael W. Vannier. "Hippocampal Atrophy in Recurrent Major Depression." Proceedings of the National Academy of Sciences of the United States of America Vol. 93, No. 9. 30 Apr 1996. Pages 3908-3913. 1 May 2009. <http://www.jstor.org/stable/39166 >.
Thomson, J. Richard. "Current Applications of Biological Science Part IV. Psychopharmacology: A Review." Bios Vol. 35, No. 3. Oct 1964. Pages 123-133. 1 May 2009. <http://www.jstor.org/stable/4606544 >.
Weissman, Myrna M., and Mark Olfson. "Depression in Women: Implications for Health Care Research." Science Vol. 269, No. 5225. 11 Aug 1995. Pages 799-801. yu1 May 2009. <http://www.jstor.org/stable/2888484 >.
Yirmiya, Raz, Inbal Goshen, Alon Bajayo, Tirzah Kreisel, Sharon Feldman, Joseph Tam, Victoria Trembovier, Valèr Csernus, Esther Shohami, Itai Bab. "Depression Induces Bone Loss through stimulation of the Sympathetic Nervous System." Proceedings of the National Academy of Sciences of the United States of America Vol. 103, No. 45. 07 Nov 2006. Pages 16876-1681. 1 May 2009. <http://www.jstor.org/stable/30051763 >.