There are certainly strong correlations between substance abuse and other mental illnesses. However, you have to dig deeper: is the patient an alcoholic because of a preexisting mental illness? Is the alcoholism just the first outward sign that was noticed by others?

There is also a strong correlation among mental illnesses: once you get one (any one), you are statistically more likely to get one or more of the others within your lifetime. It doesn't help that they are often overlapping, though (e.g. bipolar disorder type 2 - bipolar depression). From the American Psychiatric Association Practice Guidelines: "in a study of patients in psychiatric treatment in the United States, 84% of major depressive disorder patients had at least one co-occurring condition: 61% had a co-occurring Axis I condition, 30% a co-occurring Axis II condition, and 58% a co-occurring Axis III condition (978). Anxiety disorders were the most common co-occurring disorder in the prior 12 months" (http://www.psychiatryonline.com/content.aspx?aID=655908)

As a slightly different example, 80-90% of schizophrenic patients smoke. This is because the stimulating effect of nicotine tends to improve their negative symptoms by increasing dopamine levels in certain parts of the brain (for about 15 minutes or so... then they need another one).

As far as alcohol causing depression: alcohol /is/ a depressant. It binds to GABA receptors (among other receptors) and increases sedation, decreases mental activity, etc. (GABA is the primary inhibitory neurotransmitter of the brain).

Inflammation as a cause of depression is not really significant right now. Look at our classes of antidepressants: tricyclics (which work in depression by inhibiting the reuptake of serotonin and norepinephrine), selective serotonin reuptake inhibitors, selective norepinephrine reuptake inhibitors, dopamine reuptake inhibitors (bupropion is mostly what I'm going for here, though sertraline also has some dopaminergic activity), serotonin receptor agonists (e.g. trazodone), and alpha-2 antagonists (mirtazapine - it indirectly increases serotonin and norepinephrine levels by blocking autoinhibition of alpha-2 receptors in the brain). None of these have noteworthy effects on inflammation, and all of them are effective in a modest population of patients (unfortunately only about 1/3 of patients achieve remission on their first drug trial, regardless of which one). Inflammation isn't really a significant theory of depression right now, although I'm not saying it doesn't exist. Mental illnesses are unbelievably complex and medical science is only beginning to catch up with our needs.

"None of these have noteworthy effects on inflammation, and all of them are effective in a modest population of patients"

The fact that taking drugs that mess with your neurotransmitter levels can sometimes alleviate depression doesn't prove, and isn't even particularly strong evidence for, the idea that depression is caused by some sort of neurotransmitter imbalance. Wearing perfume can also alleviate depression in some people, but it would be ridiculous to claim that depression is caused by a lack of Chanel No. 5.

History time. Antidepressant pharmacotherapy was actually discovered in the 1950s when reserpine, then used as an antihypertensive, was noted to cause depression. Reserpine acts by blocking the transmission of neurotransmitters 5HT, NE, and DA. Given that over twenty drugs, all with different actions on different neurotransmitters, have shown efficacy in depressed patients over the last 60 years, I think it would be rather shortsighted to dismiss the significant body of literature dedicated to the role of neurotransmitters in depression.

There are certainly many theories, and depression is a complicated disease. It is primarily modified by neurotransmitters, however. That much should be clear. Beta adrenergic receptor sensitivity and downregulation are also involved - but to what extent? Hypersecretion of cortisol (or lack of cortisol suppression) is also a factor - but to what extent? Even thyroid hormones are implicated.

Like I said, I'm not saying there is no inflammatory problem in depression - I said that we have no antidepressants based on this idea (and as far as I know, there are none in the pipeline in at least Phase II trials). Do I think inflammation is involved? Yes, I do. Do I think it's directly going to lead to more treatments for depression? No, I don't.

"Given that over twenty drugs, all with different actions on different neurotransmitters, have shown efficacy in depressed patients over the last 60 years, I think it would be rather shortsighted to dismiss the significant body of literature dedicated to the role of neurotransmitters in depression."

Virtually every form of sensory stimulation has been shown to ease depression, from aromatherapy to acupuncture to exercise. What makes you think that neurotransmitters are the root cause of the problem? To me the fact that no matter how you mess with the neurotransmitters it eases depression shows that this is a function of sensory novelty, as opposed to some neurotransmitter imbalance being the root cause.

"There are certainly many theories, and depression is a complicated disease."

What makes you think it's a single disease?