Changes to levels of neurochemicals
Clinical Depression is often said to be caused by a chemical imbalance in the brain, and this is what most drug treatments are based on. Certainly in many cases, there is a reduction in the amount of certain neurotransmitters found (monoamines such as serotonin and norepinephrine) in depressed people.
However, low serotonin levels are simply another symtom of depression, not a cause. The more negative introspection you carry out, and the fewer pleasure-giving activities you participate in, the lower your serotonin levels become.
"Regarding depression as "just" a chemical imbalance wildly misconstrues the disorder."
Psychology Today
March, 1999
Drug therapies that work on this imbalance lift depression completely in a third of those who take them and partially in another third. For a third of people, antidepressants don't work at all, and many who do get positive results stop taking them because the side effects are worse than the depression symptoms they are supposed to be treating.
Antidepressants are also much worse at preventing relapse than appropriate psychotherapy (which is obvious, when you consider they are treating a symptom, not the cause of depression.) (1, 2)
Depression can lead to chemical changes in the brain, which return to normal once your depression lifts.
Also, we are fully aware that clinical depression is far more than a prolonged sadness, or period of grieving. Yet these chemical imbalances can be found on occasion in all of these situations.
This is why depression is not caused by chemical imbalance in the vast majority of cases.