A meeting was held on November 16

A

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.

Dr.

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.

Several

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

neurons.

Behavioral

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.

Drs.

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.

Studies

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.

The

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).

In

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.

Dr.

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.

Abstracts

with slides: