Background: Depression is one of the five most-common diseases globally, and is expected to be the second leading cause of disability by 2020 and its economic and social burden is a major problem worldwide 
Objective: The aim of this research was to elucidate the causes and symptoms of depression according to Persian Medicine (PM) and classic medicine.
Methods: In this study, works that were investigated were the Canon of Medicine, Al-Hawi Fi Teb, Kamel Al-Sina'a, Zakhireh Kharazmshahi and Exir A’azam. Classic medicine sources investigated were Kaplan and Sadock's Synopsis of Psychiatry and related articles in the Web of Science, Medline, Scopus, SID and Magiran. Research was done from January through April 2017, using keywords. 
Results:  To explain the biologic causes, various factors including humoral dystemperaments, cold and hot dystemperaments of chief organs especially heart and brain and some qualitative and quantitative changes in medical spirit should be considered. According to manuscripts some mental-emotional events in life can cause these changes. They independently may cause depression. Semiologically some symptoms and signs happen consequently to in the above-mentioned causes which are in common with depression signs and symptoms including grief, crying, low libido, weight loss, appetite and sleep disorders, exhaustion, slow cognitive processing, indecisiveness and willingness to die.
Conclusion: The major biological causes of depression is a group of dystemperamental syndromes (hot, cold, dry, and wet) on different bodily structures (humors, organs, and spirits). So preventive and therapeutic strategies for depression couldn’t be the same for all patients and the treatment should be designed according to the exact diagnosis.


Keywords: Major Depressive Disorder, Temperament, Persian Medicine


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