So, let's start at the very beginning, which is the physical basis for depression.
A really good way to understand depression is think about diabetes.
Here's a picture we've lifted from adam.com that shows a malfunctioning pancreas. This organ, that lives near your stomach, produces an extremely important hormone, insulin, which helps regulate our body's sugar levels. Too much insulin in the system makes you tired and droopy (as happens with hypoglycemics), and too little insulin causes the sugar in our bodies to rise to dangerous levels. An overabundance of sugar in our tissues causes damage, such as when it harms tissues used for eyesight, causing blindness.
The exact cause of diabetes is not known -- a combination of genetics and overall health -- but we know the effects of the condition quite well. The standard treatment for diabetes is a regimen of exercise, diet, and medicine to regulate insulin levels.