At Issue: Schizophrenia and Rheumatoid Arthritis:
The Negative Association Revisited
by Robert J. Oken and Michael Schulzer
The At Issue section of the Schizophrenia Bulletin con-
tains viewpoints and arguments on controversial issues.
Articles published in this section may not meet the strict
editorial and scientific standards that are applied to
major articles in the Bulletin. In addition, the viewpoints
expressed in the following article do not necessarily rep-
resent those of the staff or the Editorial Advisory Board of
the Bulletin.—The Editors.
A strong negative association between schizophrenia
and rheumatoid arthritis (RA), implying low comor-
bidity, has been found in 12 of 14 previous studies,
which we review. To this literature we add two
recently acquired data sets encompassing 28,953 schiz-
ophrenia patients, only 31 of whom had comorbid RA.
Integrating our new data into those of the previous
nine studies, which stratified their populations accord-
ing to psychiatric diagnosis, we obtain a median fre-
quency of RA in schizophrenia populations of 0.09 per-
cent and a mean frequency of 0.66 percent, well below
the expected range of 1 percent. These data robustly
support prior studies.
We also present a meta-analysis evaluating the
association between the two diseases by integrating
information derived from m'ne data sets, each furnish-
ing an estimate of the relative risk of RA in schizo-
phrenia patients versus that in other psychiatric
patients. We find that the estimated rate of RA among
schizophrenia patients is only 29 percent of the corre-
sponding rate in other psychiatric patients. Further,
the relative risk of RA in schizophrenia patients versus
that in the general population is even less than 29 per-
cent and could be as low as one-third of this value.
We present a new hypothesis involving the platelet
activating factor system in an effort to account for this
negative association and review the suggestions of
other investigators toward this end. Finally, we con-
sider the glutamaterg