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Is depression a disorder of a receptor superfamily? A critical review of the receptor theory of depression and the appraisal of a new heuristic model

Published online by Cambridge University Press:  16 April 2020

GB Cassano  and
D Marazziti
GB Cassano
Affiliation:
Institute of Psychiatry and II Chair of Psychiatry, University of Pisa, via Roma 67, 1-56100, Rome, Italy
D Marazziti*
Affiliation:
Institute of Psychiatry and II Chair of Psychiatry, University of Pisa, via Roma 67, 1-56100, Rome, Italy
*
*Correspondance and reprints.
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Summary

The monoamine hypothesis of depression and its direct derivation, the receptor theory, have constituted for several years a frame of reference for researchers working in the field of biological psychiatry. Although most of the data are derived from animal findings and must be considered inconclusive in view of various controversies, some guidelines may be identified: these would suggest that changes in postsynaptic beta-adrenoreceptors, presynaptic alpha 2-adrenoreceptors, as well as in type 2 serotonin receptors and dopaminergic autoreceptors may be involved in the mode of action of antidepressant drugs and, consequently, in the pathophysiology of depression. Nowadays, any attempt to correlate depression with the dysfunction of a single neurotransmitter or receptor is no longer tenable, since it is clear that depression is a heterogeneous disorder which involves abnormalities in the interactive relationships between neurotransmitters and receptors. If, on the one hand, this new model has opened up new fields of research and has led to the investigation of new systems, eg the GABAergic and GABA B receptors, on the other hand, it has been strongly limited by the lack of research tools and reliable peripheral CNS models for in vivo studies. A possible approach to this unresolved dilemma may be provided by molecular biology techniques, which have permitted the identification of the genes and sequencing of the primary structure of several membrane receptors. It is now established that receptors may be grouped into four superfamilies; in depression, there exists compelling evidence of alterations mainly in receptors belonging to the G-protein-coupled family: it is plausible that depression may be related to a disorder of the G-protein-coupled receptor superfamily. Such an hypothesis would represent an attempt to unify the different receptor abnormalities found in depression or following antidepressant treatments, and to shift from the monoamine paradigm to a new heuristic model. In addition, it would accommodate the various dysfunctions likely to be encountered and would open up new theoretical perspectives in the treatment of depression.

Keywords

depressionneuroreceptormolecular biologyG proteinsreceptor superfamily
Type
Review
Information
European Psychiatry , Volume 7 , Issue 6 , 1992 , pp. 259 - 270
Copyright
Copyright © Elsevier, Paris 1992

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