Dopamine hypofunction

There is no evidence for an elevated dopamine content or hypersensitivity of dopamine receptors in the brain of schizophrenic patients. Breakdown products of dopamine and noradrenaline are elevated neither in the urine nor in the blood or cerebrospinal fluid of schizophrenic patients. In some patients with chronic schizophrenia there is even evidence of dopamine hypofunction IKaroum et al.. 1987). 

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. 

The interaction of glutamate and its NMDA receptor with other brain neurotransmitters, including the aminergic dopamine and serotonin neuromodulators which are the main focus of this book, is very complex and only a few, simplified accounts of how NMDA receptor hypofunction... 

Jentsch JD, Roth RH. 1999. The neuropsychopharmacology of phencyclidine From NMDA receptor hypofunction to the dopamine hypothesis of schizophrenia. Neuropsychopharmacology 20 201-225. 

Thus, a GSH deficit has consequences consistent with the concept of functional disconnectivity, as hypofunction of NMDA-R and alteration of dopamine signaling have been observed. When imposed on animals during development, a GSH deficit induces also a structural disconnectivity, as revealed by the decrease in dendritic spines and parvalbumin-immunoreactivity of inhibitory intemeurons in the prefrontal cortex Finally, a transient GSH deficit during brain development causes deficits in visual recognition and olfactory integration. 

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