T helper-1 activation via interleukin-16 is a key phenomenon in the acute phase of severe, first-episode major depressive disorder and suicidal behaviors

•First episode major dysmood disorder (FE-MDMD) is a severe subtype of depression.•FE-MDMD is characterized by activation of the immune-inflammatory response (IRS)•Activated IRS pathways are primarily driven by Th-1 polarization and interleukin-16.•Elevated tumor necrosis factor signaling is another important pathway in FE-MDMD.•IL-16 or CD4 activation are promising novel drug targets to treat FE-MDMD.