Schizophrenia neurotransmitter theory

The transmethylation hypothesis depended on the psychosis of mescaline as an example of how methylated compounds similar in structure to the monoamine neurotransmitters could be psychotogenic, and demonstrated how methionine, the precursor of the methyl donor S-adenosylmethionine, could exacerbate the psychotic symptoms of schizophrenia in patients. This theory was fed by studies of the now notorious pink spot, an amine found in paper chromatography of urine extracts from schizophrenics and thought to be 3,4-dimethoxyphenylethylamine (i.e., O-methylated dopamine). Subsequent studies eventually identified this as another compound or compounds, primarily of dietary origin. Another methylated derivative erroneously proposed to be found in higher quantities in schizophrenia was dimethyltryptamine. This compound is similar in structure to LSD, the hallucinogenic nature of which was the key to the serotonin deficiency hypothesis, which proposed that the known antagonism of serotonin (5-HT) by LSD indicated that psychotic disorders such as schizophrenia may result from a hypofunction of 5-HT. 

Stahl s Essential Psychopharmacology has established itself as the preeminent source of education and information in its field. This much expanded second edition enlists advances in neurobiology and recent clinical developments to explain with renewed clarity the concepts underlying drug treatment of psychiatric disorders. New neurotransmitter systems, new theories of schizophrenia, clinical advances in antipsychotic and antidepressant therapy, new coverage of attention deficit disorder, sleep disorders, and drug abuse, and a new chapter on sex-specific and sexual function-related psychopharmacology—these are all features of this edition. 

Gram doses of nicotinamide have been used in so-called orthomolecular psychiatry as a treatment for schizophrenia, originally because of the similarities between schizophrema and the depressive psychosis of pellagra. The underlying rationale for this use is that such high doses of niacin may deplete methyl donors, and at least one of the theories of the biochemical basis of schizophrenia was that the condition is caused by inappropriate methylation of neurotransmitter metabolites to yield psychotogenic compounds (Hoffer et al., 1957). There is no independent confirmation of the efficacy of nicotinamide in the treatment of schizophrenia. 

There are currently two dominant theories as to the etiology of schizophrenia. The most popular postulates abnormal neurotransmitter receptor function within the brain and, to a large extent, concentrates on studying dopamine and serotonin. Although this theory still provides psychiatry with its best tools for dealing with psychosis, namely medications, it has proved sterile ground for developing radical new treatment approaches. 

Since the discovery of the role of dopamine (DA) as a neurotransmitter in 1958, and the observations that antipsychotic drugs arepostsynaptic DA-receptor antagonists, interest in a dopaminergic hypothesis for the pathophysiology of schizophrenia has existed. However, these theories may be more appropriately oriented toward the treatment of psychosis with antipsychotics. 

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