Neurochemical Theory 1 of Depression
‘It is not too little but actually too much norepinephrine’. First, some background orientation. If somebody constantly yells or shouts at you, you stop listening. Similarly, if you surround a cell with lots of a neurotransmitter, the cell will not ‘listen as carefully—in scientific terms the cell will down regulate (decrease) the number of receptors for that neurotransmitter, in order to decrease its sensitivity to that messenger.
For example, if you double the amount of serotonin reaching the dendrites of a cell and that cell downgrades its serotonin receptors by 50 per cent, the effects roughly cancel out. If it down regulates by less than 50 per cent, the result will be more signalling and if it down regulates by more than 50 per cent, there will be less serotonin signalling in the synapse. In other words, how strong the signal is depends on how loudly the first neuron is shouting (amount of neurotransmitter being released) and how sensitively the second neuron listens.
The theory states that in patients with depression, there is too much norepinephrine, serotonin or both in parts of the brain. What happens if you prescribe medicines that increase these neurotransmitters even more? At first, the symptoms should get worse (this happens in a number of patients). Over the course of a few weeks the dendrites say, ‘there is too much shoutings—I cannot bear it. Let us down regulate our receptors a whole lot’. If this down regulation compensates for the extra signalling, the effects of excessive neurotransmitter will go and the person starts to feel better.
Neurochemical Theory 2 of Depression
‘The problem with depressive patients is too little of norepinephrine or serotonin or both’. Remember our discussion on neuron communication—at that time, we said the transmitting neuron has receptors for absorbing some of the neurotransmitter it has released. This process known as ‘reuptake’ is critical for proper neuronal communication. Why does the transmitting neuron reuptake the neurotransmitter? One reason is to decide on how much neurotransmitter to release or whether to stop releasing the neurotransmitter.
With this as a background, we will now try to understand the theory. Give a patient anti-depressant drugs that increase the levels of neurotransmitters. Due to the increased signalling, there will be down-regulation of the receptors over a period of weeks. The main argument is the idea that the autoreceptor on the transmitting neuron will down regulate more than the receptor on the second (listening) neuron. If this is the case, the second neuron may not be listening effectively, but the first neuron will be sending out a lot more neurotransmitter.
The net result is enhanced levels of serotonin or norepinephrine and the patient feels better. For a long time, psychiatrists have used this technique to alleviate major depression using ECT (electro convulsive therapy also known as ‘shock’ treatment). In animal experimentation, it has been observed that ECT decreases the number of norepinephrine autoreceptors.
At this point in time, there is considerable research and debate going on to explain the neurochemistry of depression. The best treatment for depressives seems to be newer drugs that target both serotonin and norepinephrine depending on the dosage and the symptoms. It is also important to note that there are several other neurotransmitters implicated in depression though their role is not as clear. Recall that one of the key signs of depression is lack of ‘pleasure’ or anhedonia.
It is logical to assume that the portions of the brain involved with feelings of pleasure or sadness must have something to do with depression. In fact, there is such a region in the brain and a neurotransmitter named dopamine1 which is involved in feelings of pleasure. Some researchers have implicated problems with dopamine levels in cases of depression. However, these are tentative findings and more research needs to be done before the details are sorted out.
One of the key factors in depression is the role of psy-chological stress. Repeated studies have demonstrated a clear link between stress and the onset of depression. The body’s stress response is thought to be the main cause of disruption in the levels of neurotransmitters. A very important caveat— studies have shown that the first few episodes of depression are preceded by stressful events but after that depression takes on a cycle of its own and is no longer related to stress.
Another important point to note is that more women suffer from depression than men (ratio is almost 2 to 1). Usually, these episodes occur at times when a woman’s body undergoes changes in hormone levels—puberty, menstruation, pregnancy/delivery and menopause. A number of researchers believe such increased risks for women are tied to the great fluctuations that occur during menstruation, menopause and parturition in the two main hormones—estrogen and progesterone.
As evidence, they cite the fact that women can get depressed when they artificially change their estrogen or progesterone levels (for example, when taking birth control pills). Critically, both these hormones can regulate neurochemical events in the brain—including the metabolism of neurotransmitters such as norepinephrine and serotonin. This is a new area of research with some seemingly contradictory findings, but there is increased confidence among scientists that there is a hormonal contribution to the preponderance of female depressions.