When I started studying neuroscience I was - as any tabula rasa - convinced neuroscientists knew how to tackle the problem of depression. However they have been studying the same neurotransmitters for decades already with always the same results: not every patient reacts well to antidepressants/therapy.

Another theory, which has been around for decades aswell, is based on dysregulation of the Hypothalamic Pituitary Adrenal axis, which has led to a huge amount of inconsistent data aswell.

So, maybe there are different types of depression:
- the more environment based type, those patients can be helped with psychotherapy.
- the more 5-HT based type
- the more noradrenaline/dopamine based type
- and the HPA axis/ stress hormone type.

And to make it even more difficult: depression in the elderly and/or depression in people suffering from cardiovascular disorders (is depression just a prodrome or a causal factor?).

Unfortunately - like with everything in neuroscience - most of the time it will be mixed types, especially because everything is interconnected and both internal and external factors interact.
What do you think?

I think boosting neurotransmission, including cholinergic, adrenergic and dopaminergic transmission, should solve most people's depression regardless of cause.

Would you really consider that solving depression? I call that covering up symptoms. The base problem still exists, and in most cases I believe could be cured with proper nutrition and an orthomolecular approach.

if you believe that psychological causes underlie the depression, then getting at the root psychological causes might help. However, most depression is probably due to depressed physiology, which can be remedied through enhancing certain modes of neurotransmission. Proper nutrition is a more indirect approach that probably wouldn't work in most cases; otherwise, people wouldn't be taking prozac or other mood enhancers. I'm not trying to justify prozac; I'm just saying it's probably more effective than diet or orthomolecular approaches.

Check out the book, The Brain Chemistry Diet, by Dr. Lesser M.D.. He cites studies in which vitamins and a proper diet can be as effective as prescription drugs. There are a few key points, namely balancing copper and zinc levels, stablizing vitamin C levels, and ensuring adequate consumption of B vitamins (especially folic acid and niacin).

The United States is one of the most overfed yet malnourished countries in the world. Obviously people will get depressed when they are loaded with saturated fats and refined carbohydrates.