Disturbances in central serotonin (5-hydroxytryptamine, 5-HT) were first described in depression. They were inferred to exist based on the finding of lowered baseline and post-probenecid concentrations of 5-HIAA in CSF. Initially, depressed patients with and without deimonstrable disturbances in central 5-H1 seemed psychopathologically indistinguishable. Interpreting the available data, at that time, we introduced in 1971 the concept of biochemical heterogeneity of depression. Some forms, we postulated, are linked to disturbances in 5-HT functions, others are not or, to a much lesser extent. Subsequently, we showed the concept of a separate «5-HT depression» to be untenable. It seems more likely now that 5-HT disturbances in depression are not linked to a particular syndromal depression type, but to particular psychopathological dimensions, i.e. heightened anxiety and disturbed aggression regulation. These dimensions might form a prominent aspect of depression or may be virtually absent. They are moreover not specific for depression, but can occur in other psychiatric disorders as well. This might explain the seemingly capricious occurrence of 5-HT disorders in depression as well as their nosological non-specificity.
Based on the dimensional 5-HT hypothesis one might expect drugs that increase 5-HT availability in the brain to be effective in the various anxiety disorders, in depressions marked by increased anxiety and disturbed aggression regulation and in personality disorders with strong aggressive tendencies.