Hypothesis for Mechanism of Sex Differences in Depression

Hypothesis for Mechanism of Sex Differences in Depression

Depression is one of the most debilitating disorders affecting millions of people worldwide. However, some mystery remains in the etiology and treatment of depression. One of the unveiled mysteries is the mechanism and extent of sex differences in depression. An obvious sex difference in depression has three evidences as follows: (A) The incidence of depression for girls rises from age 11 to 13 years until by the age of 15 years is one of the most robust findings in psychiatric epidemiology revealing that females are twice as likely to suffer from depression than males. (B) Men are more liable to have persistent depression, whereas women tend to suffer from a more episodic disorder. (C) Depressed men are also more likely to commit suicide and to abuse substances than depressed women.Knowing the overt sex difference of depression in incidence and symptoms, I suggest that sex differences in depression also possibly have its psychophysiological mechanism affecting treatment choices. However, treatment guidelines of depression do not take sex differences into consideration.Current evidence indicate differences in inflammatory profiles, molecular signatures, and treatment responses toward antidepressants in depressed men and women. Based on the above noted findings, I hereby propose the external/internal model (E/I Model) for the sex difference in depression, i.e., more pronounced impairment in response to external stimuli (e.g., social interaction) in depressed women; and more conspicuous abnormality responding to internal thought (e.g., self contemplation) in depressed men. Consequently, sex specific depression treatment should be implemented, such as interpersonal therapy in women and meditation in men.