The symbols can be translated as follows:



Electrical currents: In reality, the current is generated by depolarizations of cell membranes that are adjacent to each other. Small packages of neurotransmitters are secreted into the tiny spaces between brain cells (neurons) where it leads to the creation of microscopic currents in adjacent nerve cells. The current thus spreads from one cell to another; a microscopic chain reaction.


Electrical outlets: In reality these are post-synaptic receptors on the nerve cells. Receptors are proteins on the outside of nerve cells that get turned on by specific substances (neurotransmitters) that bind to them.  Synapses are the tiny gaps between brain cells where they interact with each other via the secretion of the neurotransmitters. In depressed patients, there is an increased number of post synaptic receptors generated. In treated depressed patients, over 1-2 weeks there is a reduction in the number of these receptors in a process called down regulation. Feeling better often tends to correspond with this down regulation process, or some other process we don't understand, which is why there is often a delay of 1-2 weeks between the time one starts taking an antidepressant and the time when one actually starts to feel better from it.


Neurotransmitters: The main neurotransmitter system affected by Celexa is serotonin. The six medications listed are part of a class called the Selective Serotonin Reuptake Inhibitors (SSRIs). By blocking the re-uptake of serotonin, the medications increase the amount of serotonin in the synapses between the cells thereby increasing the serotonin current. Thus starts the cascade that results ultimately in a renewed equilibrium.


Autoreceptors: There is new research that hints at more complicated issues than the above simple schematic. Serotonin (5-HydroxyTryptophan or 5-HT) binds to at least 15 different subtypes of receptors in the brain including slow down or autoreceptors. One subtype in particular has received a lot of scrutiny and it is called the 5 HT 1A autoreceptor. This receptor is sometimes located on the secreting nerve cell. If you think of baseball, this secreting cell is analogous to the "pitcher", as opposed to the post synaptic or "the catcher" receptor. 5 HT 1A acts to slow down the pitching of serotonin balls as it were. One theory is that SSRI medications work by so bombarding this slow down mechanism with serotonin that it starts to shut down. Then the pitcher, without this braking mechanism, starts throwing more pitches of serotonin across the plate, and you feel better eventually. In some people, this theory goes, their slow down mechanism does not get shut down or desensitized by medication and therefore in these unfortunate folks, SSRIS do not work so well. The technical term for this phenomenon is hence called the desensitization of serotonergic autoreceptors mechanism of action.



Second Messenger Systems: Basically thinking of the pitcher and catcher, the catcher cell after it catches the serotonin ball, has its own set of reactions. These are complicated and involve a cascade of chemical reactions involving the enzyme adenylate cyclase, Cyclic AMP (cAMP) and other microscopic intracellular substances. These chemical reactions may be important to the mechanism of action.


Hypothalamic Pituitary Axis (HPA): This is a different ball of wax involving the concept that a difficult childhood may lead to an overactive cortisol system, specifically an increase in Corticotrophin Releasing Factor(CRF). Maybe antidepressants work by decreasing CRF.


THE WEB: Maybe it is not the serotonin current alone but a complex web involving multiple currents that is affected. Alternatively, maybe we are lumping together many distinct subtypes of depression when in reality different subtypes have entirely different mechanisms of action. Then there would not be "one" mechanism of action, but several. We don't know.