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LETTERS TO THE EDITOR
Pregnancy, Schizophrenia and
Rheumatoid Arthritis
SIR—That certain conditions can influence the clinical
course or occurrence of RA provides a unique
opportunity to learn more about the nature of the
disease. Of these conditions, pregnancy, which in most.
women ameliorates the disease, has provoked the
greatest interest. In a recent editorial [1], the focus to
explain a relationship between pregnancy and RA was
on the action of inflammatory cytokines. I wish to
point out that metabolic changes such as lower cellular
glutathione (GSH) concentrations, as well as immune
events, modulate the inflammatory type response in T
lymphocytes [2]. The cellular GSH concentration is
regulated, in part, by serum thiols which include GSH,
cysteine, cysteinyl-glycine and homocysteine (hyc). Of
particular interest here is hyc, which has a profound
effect on plasma redox thiol status [3] and whose
concentration in serum is increased transiently in RA
patients receiving methotrexate [4]. Most interesting is
that the total serum hyc concentration decreases during
pregnancy, becoming maximal in the second trimester,
to ~50% of the level in non-pregnant women [5]. After
parturition, its concentration returns to normal.
A second condition is schizophrenia in which there
is a low frequency of RA. In a review of 14
epidemiological studies of the relationship of RA to
schizophrenia, the authors conclude that the data were
not perfect, but were good [6]. Methylation deficiency
comprises a prominent theory to explain schizophrenia.
The administration of methyl-labelled methionine to
603'
schizophrenic patients showed that the rate and total
expiration of labelled CO2 were three times less in the
patients than in the controls [7]. That this aberration
involves hyc metabolism is confirmed by a recent case
report of homocysteinaemia and schizophrenia [8].
These findings raise the possibility that the inciting
agent in RA is metabolic changes which affect the
redox status of cells.
G. W. RAFTER
Department of Biochemistry, West Virginia University,
School of Medicine, Morgantown, WV 26506-9142,
USA
Accepted 30 October 1995
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Herzenberg LA. Redox regulation of signal transduction:
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USA 1994;91:3619-22.
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evidence for abnormal methyl metabolism in schizophrenia. Bio!
Psychiatry 1992^2:1078-90.
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schizophrenia as a case of methylation deficiency. J Neural
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