Posted by Cam W. on October 29, 2001, at 16:23:49
In reply to Re: Thanks to Cam, posted by medlib on October 26, 2001, at 15:34:50
Med - I thought that I posted to this, yesterday, but it didn't show up (Hmmmm....). I haven't read the Serotonin chapter in the online psychopharmacology text, but I will relate some of what I know about the actions of neurotransmitters in relation to one another (this is my view of it, and it would be nice if someone with a better grasp of the interconnective relationship between neurotransmitters could fill in the blanks and make corrections).
I look at all neurotransmission as eletrical pulses of varying intensity. These pulses can be separated in strengths, depending on the action of the pulse and what kind of nerve is carrying that pulse. The two most common pulses seem to be 40Hz and 2-3Hz. These pulses have different activities and transmit signals with different meanings. It is this electrical activity that causes our movements, thoughts, and feelings.
There are two basic neurotransmitters in the brain; glutamate and GABA (gamma-amino-butyric acid). All other neurotransmitters (like dopamine, serotonin, acetylcholine, and norepinephrine; which really should be called neuromodulators), modify the effects of these glutamate and GABA. These neurotransmitters can also modify the action of the other neurotransmitters, as well. Therefore, there is an elaborate interplay amongst all of the 100's of neurotransmitters (incl. peptides, proteins, nitric oxide, etc).
The reason I pick out glutamate and GABA is because glutamate's main action is excitory. It stimulates other nerves, to which it is connected, into firing. GABA, on the other hand is an inhibitory neurotransmitter, thus slows the electrical transmission of neurons.
In addition to speeding up and slowing down of neurons, the brain needs to modify signals so that these signals will act at a certain brain structure, with a certain intensity. This is the job of neurotransmitters and neuromodulators. Since we always are talking about mood, energy and drive on this board, we most often talk about the neurotransmitters that control these systems: serotonin, dopamine, and norepinephrine.
For example, a serotonin neuron is stimulated to fire by electrical imput from glutamate acting on NMDA receptors (either primarily via NMDA receptors on the serotonin neuron, or secondarily through some other neuroreceptor-containg neuron). Several othe neurotransmitters have a variety of different receptors imbedded into the surface of our serotonin neuron. The firing (or blocking) of these receptors changes the electrical activity of our serotonin cell, ultimately causing our cell to either release a large amount of serotonin from it's synaptic terminal (and hence propagate or carry on the electrical signal to the next neuron) or to stifle the electrical signal (and our serotonin neuron does not release any serotonin). Between these polar situations, there are also a spectrum of different possibilities of what our neuron could do, which results in the exchange of electrical activities (and serotonin release) of varying degrees.
It is the action of various neurotransmitters regulating each other in countless configurations in both sensory and motor neurons, that makes us, us. For example, Serotonin regulates dopimine flow (and vice versa) for determining how aggressive one is, or how sexual one is. The serotonin input involves impulsivity and the dopamine input involves pleasure and drive. The synaptic interconnections (amount, type, and quality of) between dopamine and serotonin, and the nature of the electrical flow between neurons containing each of these neurotransmitters, determines how aggressive one is, or how sexual a person is.
The above is incredibly simplified. These systems (impulsivity and sexuality) are also modulated by other neurons and neuromodulators from various other brain regions. The brain (like the Earth) acts like an organism, where affecting one part ( neurotransmitter system, brain area, neurotransmitter concentrations, specific receptor subtype concentration) affects the whole brain. The brain can lose proper function due to injury; which can be due to physical reasons (physical trauma) or due psychological reasons (psychological trauma).
Psychological trauma occurs when a neuronal system(s) in the brain becomes overburdened or overstressed. Brain neuron systems have a maximum capacity, after which they start to break down. The brain's other component's trying to counteract the overactivity (stress) of the brain area by modifying neuron-induced electrical flow to the area, while at the same time trying to compensate for the loss or reduction of activity from the overloaded neuronal system.
For example, the HPA axis (Hypothalamus-Pituitary-Adrenal) is thought to control the body's response to stress. It initiates the body's automatic "fight or flight" response. When overtaxed or overwhelmed by stress (environmental, as well as psychological), the HPA axis starts to malufunction. This malfunction can occur in different ways and different outcomes can be measured. For exmaple, in some cases, there will be uncontrolled cortisol release from adrenals, and this may result in a deadening (or even a down-regulation) of glucocorticoid receptors in the hypothalamus and pituitary. Thus the feedback mechanism (cortisol stimulation of the above glucocorticoid receptors) which turns off the cortisol flow is dysfunctional, so the cortisol flow is not turned off, and eventually this system collapse results in the symptoms that we call depression. The body has not been able counter or reverse the stress it is receiving; the body's homeostatic mechanisms breakdown; depression ensues.
The malfunction can occur at other parts of the HPA axis (ACTH-receptor deadening) or even through other brain systems related to, and interconnected with, the HPA axis. In many cases, no matter what or where the breakdown is or what part is "broken", the final set of symptoms (eg. symptoms of depression) will look similar. In other words, many widespread and different neurochemical breakdowns can each result (as an overt endpoint) in similar symptomatology (ie. depressive symptoms).
This complexity is partially why I do not think that the monoamine theory of depression is correct. Serotonin, norepinephrine and dopamine are only part of the show. Low brain serotonin levels, while seen in depression, do not necessarily mean that low serotonin "causes" depression. There have been studies that have refuted this. We have found that in many people diagnosed with depression, when we return serotonin to the body (using a SSRI) the depression resolves, but not in everyone.
I look at adding to serotonin to a depressed brain, as being a piece of wire splicing together a malfunctioning electrical cord. The serotonin from the SSRI allows some areas of the brain to funtion better. The low serotonin that we see in the spinal cord of some people with depression may actually be a result of depression and not a cause. But, maybe by adding back serotonin into the system, the part that has broken down can slowly mend, because the increase in serotonin is altering the levels of all the other neurotransmitters and neuromodulators, by interacting with them. The interaction of the increased serotonin may help push the body back to a state of homeostasis, and the depression resolves.
The above is a guess, I really should have consulted some papers, but I am too lazy. Work has been a little rough. I have been working 12 hour days, with only a day off here and there. I am catching on to the computer system, and begininng to get a feel for my patients and docs. I am finding the overall work much easier than my last job. I am not positive that I want to go back and work in mental health again. I am finding that I can make a difference in the mental health of the minority of people with mental illness who use the store I work at. Word of mouth is already getting around this fairly large farming community (only 5000 people in town, but at least twice to 3 times that in surrounding areas). I am already being asked to talk to several people about their depression and their antidepressants.
Like I said, so far I am liking it. After 13-14 years, everyone needs a change. I do feel much better about myself, and do believe that I am growing, as a person.
Thanks for asking, everyone - Cam
poster:Cam W.
thread:13010
URL: http://www.dr-bob.org/babble/social/20011025/msgs/13113.html