Anxiety and increased aggression as pacemakers of depression

The concept of a serotonin (5-HT)-related, anxiety and/or aggression-driven, stressor-precipitated depression is formulated and discussed. The serotonergic disturbances found in some depressed individuals, particularly those with lowered CSF 5-HIAA, are linked to the anxiety and aggression components of the depressive syndrome. In this type of depression, called 5-HT-related depression, dysregulation of anxiety and/or aggression is hypothesized to be primordial and mood-lowering is a derivative phenomenon. In other words, this is a group of anxiety/aggression-driven depressions. The author submits that the serotonergic impairment in certain types of depression is a trait phenomenon, i.e. it persists during remission. This disturbance makes the individual susceptible to perturbation of anxiety and aggression regulation. Anxiety and (overt or suppressed) anger are core constituents of the stress syndrome. Thus the serotonergic disturbance will induce a heightend sensitivity to stressful events, i.e. the latter will induce stress phenomena, including anxiety and anger, more readily than normal. The latter psychological features induce lowering of mood, and thus 'drive' the patient into a full-blown depression. Furthermore, it is predicted that anxiolytics and serenics (i.e. anti-aggressive drugs) that act via normalization of serotonergic circuits will exert an 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 serotonergic impairment in 5-HT-related depression has yet to be elucidated.