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We and others have shown that in vitro tryptoline (tetrahydro-beta-carboline) formation accounts for the apparent-N-methylating activity of a brain enzymatic preparation using 5-methyltetrahydrofolic acid (5-MTHF) as a cofactor and tryptamines or catecholamines as substrates. This paper demonstrates that N5,10-methylenetetrahydrofolate reductase (methylene reductase) is responsible for this in vitro tryptoline formation with human brain enzymatic preparations. Others have described a folate-responsive psychosis which was associated with markedly reduced methylene reductase activity. Therefore, we also have examined this enzymatic activity in autopsied brains from chronic schizophrenics and controls. There were no statistically significant differences between activities for schizophrenics and controls in the six brain regions studied. Thus, although it is possible that some subgroup of schizophrenics may be characterized by abnormal methylene reductase activity, there does not appear to be a general association between the two.

An inbred colony of narcoleptic doberman pinschers has been analyzed for muscarinic receptor levels in 19 discrete brain regions. In comparison to age-matched controls, receptors were generally elevated in the brainstem and reduced in forebrain areas. No changes in receptor binding affinity were detected. The increased receptor levels found in the brainstem suggest that cholinoceptive neurons in this region are hypersensitive and may be involved in the initiation of cataplexy and other aspects of the narcolepsy syndrome.