[Current biochemical hypotheses of endogenous depression].

In this short introductory review the current important working hypotheses of depression, the noradrenaline and serotonin hypotheses, are described and critically evaluated. Anticholinergic properties, co-modulation of various transmitters by different neuropeptides, great variations in the influence on the "re-uptake" mechanism for noradrenaline and serotonin with no effect by novel antidepressants like iprindole, mianserin and clenbuterol and variability to either stimulate or block receptor systems (alpha 1-, alpha 2-, beta-, serotonin-, dopamine-, adenylate cyclase dependent-, histaminergic receptors and possibly others) might further indicate a complex pathobiochemical background to depression. More recently, a unified hypothesis has been presented on the basis of subsensitivity of the noradrenaline-sensitive adenylate cyclase and/or down regulation of the number of beta-receptors by antidepressants of otherwise different pharmacological properties. Furthermore, another hypothesis, the "brain area specific imbalance of neurotransmitter systems" tries to combine current knowledge of the biochemistry of depressive disorders, the different pharmacological profiles of antidepressants and the divergence of symptomatology in depressed patients. Since antidepressant activity of drugs is dependent on the functional state of pre- and postsynaptic neurotransmission it seems essential to define the basal activity of such systems in vivo and to study the functional change after therapy. Furthermore, phenomena like adaptation and tolerance must be considered in future research in order to get more detailed information about pathobiochemical processes causing depression.