Serotonin, depression, and aggression: The problem of brain energy
Anyone who has been reading the mass media and watching television in recent decades is familiar with the use of tryptophan as an antidepressant. Tryptophan is easily converted to serotonin and melatonin in the body. The most popular kind of antidepressant, the “serotonin reuptake inhibitor”, is said to act by increasing the action of serotonin in the brain. Many people have read articles in popular science magazines explaining that a deficiency of serotonin can cause depression, suicide, and aggression. Estrogen is often said to achieve its “wonderful” effects by increasing the effects of serotonin.
Reserpine is an ancient tranquilizer, derived from a plant used in India for centuries. It has a powerful tranquilizing action, has been used to treat hypertension, and was found to be an antidepressant (Davies and Shepherd, 1955). It lowers the concentration of serotonin in the brain and other tissues.
But the term “antidepressant,” as distinguished from “tranquilizer,” says that the drug is intended to relieve depression. Injecting serotonin never does that, but sometimes adrenalin or dopamine does, and these “SSRI” drugs increase the activities of those other amines enough that those changes could explain the altered mood, if it weren’t for the need to speak of a “new generation of drugs.” Injecting serotonin, or increasing its activity, can cause sedation, helplessness, or apathy, but these drugs have that effect only some of the time. Therefore, they aren’t called tranquilizers. If they were really selective for serotonin, they just wouldn’t be antidepressants. And chemicals that antagonize serotonin do seem to function as antidepressants (Martin, et al., 1992).
Serotonin: Effects in disease, aging and inflammation
Women have migraines more often than men do, and they tend to occur in association with ovulation or menstruation. Estrogen inhibits monoamino oxidase, MAO, especially the A form that is most active in detoxifying serotonin, and it increases the enzymes that control the rate of serotonin synthesis. During serotonin excess, the veins and capillaries of the pia mater are engorged with blood, while circulation to the brain generally is depressed. Visual symptoms are probably produced by contriction of arterioles, while the pain is associated with engorged veins. Progesterone activates the MAO-A, and has other antiserotonin effects on blood vessels and nerves.
Recently (Shansky, et al., 2010; Figueiredo, et al., 2007), females have been found to be more susceptible to stress, and to have reduced uptake of serotonin (prolonging its effects), which increases glucocorticoids and ACTH. Kendler, et al. (2005) have found that people with reduced serotonin uptake are more susceptible to stress-induced depression.
Tryptophan, serotonin, and aging
The fatigue produced by “over-training” is probably produced by a tryptophan and serotonin overload, resulting from catabolism of muscle proteins and stress-induced increases in serotonin. Muscle catabolism also releases a large amount of cysteine, and cysteine, methionine, and tryptophan suppress thyroid function (Carvalho, et al., 2000). Stress also liberates free fatty acids from storage, and these fatty acids increase the uptake of tryptophan into the brain, increasing the formation of serotonin. Since serotonin increases ACTH and cortisol secretion, the catabolic state tends to be self-perpetuating. This process is probably a factor influencing the rate of aging, and contributing to the physiological peculiarities of aging and depression.
Theanine May Treat Depression In Humans
It is a human study, and it used a relatively low dose theanine - only 250mg daily for 8 weeks. Theanine improved virtually all symptoms including actual symptoms of depression, anxiety, and cognitive function. I wonder what would double that dose have achieved given the study I posted about theanine BOTH reducing serotonin and increasing dopamine.