Serotonin-related, anxiety/aggression-driven, stressor-precipitated depression. A psycho-biological hypothesis.

The concept of a 5-HT related, anxiety and/or aggression-driven, stressor-precipitated depression is formulated and discussed. It comprises the following elements. The 5-HT ergic disturbances found in some depressed individuals - and of them particularly lowered CSF 5-HIAA - are linked to the anxiety- and the aggression-components of the depressive sydrome. In this type of depression - called 5-HT related depression - dysregulation of anxiety and/or aggression are primordial and mood lowering is a derivative phenomenon. In other words this is a group of anxiety/aggression-driven depressions. The 5-HT ergic impairment in certain types of depression is a trait-phenomenon, ie, persists during remission. This disturbance makes the individual susceptable for perturbation of anxiety- and aggression-regulation. Anxiety and (overt or suppressed) anger, are core constituents of the stress-syndrome. Thus, the 5-HT ergic disturbance will induce a heightened sensitivity for stressful events, ie, the latter will induce more readily than normal, stress phenomena , among which anxiety and anger. The latter psychological features induce lowering of mood and thus "drive" the patient into a fullblown depression. Furthermore it is predicted that anxiolytics and serenics (ie, anti-aggressive drugs) that act via normalisation of 5-HT ergic circuits, will exert a antidepressant effect in 5-HT related depression, in addition to their therapeutic actions in anxiety disorders and states of increased aggressiveness, respectively. The exact nature of the 5-HT ergic impairment in 5-HT related depression has yet to be elucidated.