Causes of Major Depressive Disorder. Part of the series: Mental Health & Behavior. The causes of major depressive disorder are often chemically-based, but they can sometimes be thinking-based, much like normal depression. Understand what causes the short-term, very intense symptoms of major depressive disorder with information from a licensed mental health counselor in this free video on mental health conditions. Read more: http://www.ehow.com/video_4791045_causes-major-depressive-disorder.html