meeting was held on November 16-17, 2000 which focused on the possible role of
Toxoplasma gondii in serious human psychiatric diseases such as
schizophrenia and bipolar disorder. Presentations were made by 24 investigators
working in different aspects of the epidemiology, pathology, and molecular
biology of Toxoplasma infection and human brain diseases. The following is a
summary of the presentations. Abstracts and slides follow.
Yolken, the organizer, opened the meeting by summarizing evidence suggesting
that many cases of schizophrenia, and perhaps of bipolar disorder as well, may
be caused by infectious agents. Dr.
Torrey then provided an overview of epidemiological aspects of schizophrenia and
bipolar disorder that are consistent with an infectious etiology in general and
with toxoplasmosis and transmission by cats in particular.
presentations focused specifically on Toxoplasma gondii.
Dr. Barta discussed the history of the organism, its position in the
evolution of parasites, and its life cycle and basic features.
Man is an intermediate host, and the cat species is the definitive host. Dr. Carruthers described its mechanisms of cell invasion
using various proteins and noted that the retinitis that sometimes follows
congenital toxoplasma infection may not begin until adolescence. Drs. Halonen and Daubener each described aspects of
toxoplasma’s effects on the brain, including its effect on IFNγ, TNFα,
and IDO as well as its greater affinity for glia, especially astrocytes, over
effects of toxoplasmosis in the brain were described by several speakers.
Dr. Holliman reviewed rodent studies that have demonstrated altered
behavior in mice and rats infected with this parasite.
Dr. Flegr summarized several studies that compared individuals who have
toxoplasma antibodies with individuals who do not; the former have significant
differences on personality questionnaires, although the effects on males and
females are not identical. Dr.
Gilmore noted that in his study, humans with toxoplasma antibodies appear to
have a modestly lower IQ, and Dr. Dickerson reported some preliminary results
suggesting mild cognitive impairment associated with toxoplasma antibodies.
Frenkel and Apt each discussed various aspects of toxoplasma infections in
humans, specifically congenital infections, acute primary infections in adults,
recurrent infections due to immunosuppression or AIDS, and latent infections.
Much discussion focused on the nature of cysts and their possible
metabolic activity. Issues of
diagnosis were also prominent with various diagnostic problems discussed in
presentations by Drs. Frenkel, Apt, and Ford, especially the interpretation of
IgM seropositivity. Dr. Weiss
provided a broad overview of methods for diagnosis infectious agents in the
brain in general.
specifically linking toxoplasma antibodies and individuals with schizophrenia
were summarized by Drs. Gilmore and Gu, Buka, Ford, and Torrey.
Affected individuals have had greater exposure to toxoplasma than have
non-affected individuals as measured by toxoplasma antibodies in their serum or
cerebrospinal fluid. Dr. Buka
described the Collaborative Perinatal Project, which affords an opportunity for
examining sera obtained during pregnancies that occurred in 1959–1966 for
offspring who have subsequently developed schizophrenia or bipolar disorder.
Dr. Norgaard-Pedersen described a similarly exciting research resource of
PKU-screening filter paper blood samples, which have been saved in Denmark since
1980 and can now be used to measure antibodies against toxoplasma for
individuals who have developed psychiatric disorders.
final set of presentations focused on the treatment of toxoplasmosis.
Dr. Brando summarized studies showing that many antipsychotics and mood
stabilizers used for individuals with schizophrenia and bipolar disorder also
are effective anti-toxoplasma agents. Dr.
Boronow reviewed the antipsychotics and mood stabilizers that are commonly used
in schizophrenia and bipolar disorder and what is known about their mode of
action. Dr. Hughes discussed the
merits of the various anti-toxoplasma drugs currently available, including the
problem of eradication of cysts. Dr. Hinze-Selch summarized issues relating to
design and ethical aspects of drug trials.
And details of planned or potential drug trials using anti-toxoplasma
agents to treat individuals with schizophrenia, added to their existing
antipsychotics, were presented by Dr. Dickerson (Baltimore), Dr. Phillips
(Australia), and Dr. Knable (Ethiopia).
summary, there was agreement that some association exists between infections
with toxoplasmosis and schizophrenia, and possibly also with bipolar disorder.
It remains to be elucidated, however, whether this association is causal,
or whether individuals who develop schizophrenia have personality
characteristics or lifestyles that would make it more likely that they would be
exposed to toxoplasmosis.
Yolken was strongly commended for organizing and hosting the meeting, and the
participants were commended for being attentive intermediate hosts of the
parasite and the presentations.