Is serotonin conclusively linked to depression? Some highlights from the article &quot;The Depressing News about Anti-Depressants&quot;:

ever since a seminal study in 1998, whose findings were reinforced by landmark research in The Journal of the American Medical Association last month, that evidence has come with a big asterisk. Yes, the drugs are effective, in that they lift depression in most patients. But that benefit is hardly more than what patients get when they, unknowingly and as part of a study, take a dummy pill—a placebo. As more and more scientists who study depression and the drugs that treat it are concluding, that suggests that antidepressants are basically expensive Tic Tacs.
One team of researchers wondered if antidepressants were &quot;a triumph of marketing over science.&quot; Even defenders of antidepressants agreed that the drugs have &quot;relatively small&quot; effects. &quot;Many have long been unimpressed by the magnitude of the differences observed between treatments and controls,&quot; psychology researcher Steven Hollon of Vanderbilt University and colleagues wrote—&quot;what some of our colleagues refer to as 'the dirty little secret.' &quot;In Britain, the agency that assesses which treatments are effective enough for the government to pay for stopped recommending antidepressants as a first-line treatment, especially for mild or moderate depression.
But if experts know that antidepressants are hardly better than placebos, few patients or doctors do. Some doctors have changed their prescribing habits, says Kirsch, but more &quot;reacted with anger and incredulity.&quot;
Doctors see with their own eyes, and feel with their hearts, that the drugs lift the black cloud from many of their depressed patients. But since doctors are not exactly in the habit of prescribing dummy pills, they have no experience comparing how their patients do on them, and therefore never see that a placebo would be almost as effective as a $4 pill. &quot;When they prescribe a treatment and it works,&quot; says Kirsch, &quot;their natural tendency is to attribute the cure to the treatment.&quot; Hence the widespread &quot;antidepressants work&quot; refrain that persists to this day.
Right about here, people scowl and ask how anti-depressants—especially those that raise the brain's levels of serotonin—can possibly have no direct chemical effect on the brain. Surely raising serotonin levels should right the synapses' &quot;chemical imbalance&quot; and lift depression. Unfortunately, the serotonin-deficit theory of depression is built on a foundation of tissue paper. How that came to be is a story in itself, but the basics are that in the 1950s scientists discovered, serendipitously, that a drug called iproniazid seemed to help some people with depression. Iproniazid increases brain levels of serotonin and norepinephrine. Ergo, low levels of those neurotransmitters must cause depression. More than 50 years on, the presumed effectiveness of antidepressants that act this way remains the chief support for the chemical-imbalance theory of depression. Absent that effectiveness, the theory hasn't a leg to stand on. Direct evidence doesn't exist. Lowering people's serotonin levels does not change their mood. And a new drug, tianeptine, which is sold in France and some other countries (but not the U.S.), turns out to be as effective as Prozac-like antidepressants that keep the synapses well supplied with serotonin. The mechanism of the new drug? It lowers brain levels of serotonin. &quot;If depression can be equally affected by drugs that increase serotonin and by drugs that decrease it,&quot; says Kirsch, &quot;it's hard to imagine how the benefits can be due to their chemical activity.&quot;

Is this article true?  What evidence is there that serotonin is linked to depression?
It's all about the receptors, really.  There are 7 families of serotonin receptors that perform different functions within the brain, and according to Wikipedia 14 different subtypes have been discovered. 

The article assumes that a blanket level of serotonin would be sufficient to "perk" up the brain, wherein it is much more complicated.  Serotonin serves to modulate the level of excitation or inhibition depending on the circumstances.  Most of the "effect" from today's antidepressants is related to modulating projections from the dorsal raphe in the brainstem to dopaminergic neurons in the frontal cortex, but some of the serotonergic neurons in the basal ganglia can be hyperactive in situations where there is mild psychosis.  So, depending on the etiology of the depression, suppressing those neurons local to that portion of the anatomy can actually be helpful.

So, it's less to do with the transmitter that is being discussed, and everything to do with which subtypes of receptors are being agonized or antagonized.  While we have learned a tremendous amount about the relationships between neurotransmitters at different nuclei, we still have a lifetime or more of research to go.