[The serotonin hypothesis of depression]

Current theoretical and experimental developments in serotonin research extend from the differentiated description of central cytoarchitectonic structures over the identification and characterization of multiple receptor subtypes by pharmacological and molecular biological methods to the elucidation of neurobiochemical and physiological mechanisms of interneuronal communication and postreceptor signal transduction. These advances parallel the modification and optimization of various strategies for researching the relevance of central serotonergic neurotransmission in the aetiopathogenesis of affective disorders. Strategies such as the paradigm of selective pharmacological provocation contribute significantly to the formulation of complex hypotheses on the physiological regulation of receptor sensitivity, on receptor function in depression and on the processes of therapeutically induced neuroadaptation. In addition it appears that the generation of hypotheses receives further input from fundamental advances at the level of molecular pharmacology and biology. Reviewing and integrating our current knowledge to define the present state of the art facilitates the assessment of the position of serotoninergic function in the pathophysiology of affective disorder and in the mechanisms of action of various therapeutic measures.