Neurochemical and receptor theories of depression.

The neurochemical and receptor theories relate depression to deficient neurotransmission at critical sites in the brain. While this concept has generated a number of theories of depression over the years, the research findings do not fully support any single theory in its entirety. Several issues thus remain controversial or inconclusive. For instance, the monoamine deficit theory is supported by low urinary MHPG in some forms of bipolar, but not unipolar depression. Cerebrospinal fluid MHPG and 5-HIAA studies are inconclusive. Amine metabolite research is also limited in scope because the information derived pertains to pre-synaptic and synaptic events and ignores post-synaptic events. Receptor research, which includes study of both pre-and post-synaptic sites, suggests supersensitivity of Beta-adrenergic receptors in depression. But this research is criticized because it is mostly animal based. Also, the findings of low melatonin in depression contradict the supersensitivity-hypothesis. Abnormally low post-synaptic alpha-2 adrenoceptors is indicated by findings of an attenuated GH response to clonidine. But abnormality of pre-synaptic alpha-2 adrenoceptor functions has not been demonstrated conclusively. Recent findings in depression suggest a dysregulation in the dynamic and interactive relationship between neurotransmitters and receptors. Accordingly, a comprehensive view of the abnormalities of the various neurotransmitter systems in depression requires studies which investigate pre- and post-synaptic events simultaneously, preferably during illness and remission.