Toxoplasmosis and psychiatric disorders

Tanvir Singh, MD
Alina Rais, MD
T. Rais, MD
All are Assistant Professors in Dept. of Psychiatry,
University of Toledo Medical Center,
Toledo, Ohio, USA

A literature review to trace the evidence which links the protozoan Toxoplasma gondii to major psychiatric conditions. And to formulate a hypothesis to support influence of toxoplasmosis in psychiatric disorders.

Key words- “Toxoplasmosis,” “Toxoplasmosis and psychiatry”

Introduction
Recently there has been renewal of interest in “infectious causation” of psychiatric disorders. And one of the organisms, which have received special attention, is toxoplasma gondii. This is primarily because of its wide prevalence and special affinity for brain tissue. Estimate is that 30-60 percent of humans are infected with toxoplasma gondii. (1) Though most of them do not show any noticeable effect (1).

Life cycle and transmission of Toxoplasma gondii.

Toxoplasma gondii is an intracellular parasite of the family Coccidia.
The sexual phase of life cycle occurs in the intestinal tract of cat, which is
definitive host while the asexual phase occurs in the central
nervous system of intermediate host. (Human, mouse, sheep, birds, pig)
Sexual replication leads to production of oocyst which are passed in cat
feces and sporulate in soil. After ingestion by intermediate host, asexual
replication occurs, initially as rapidly dividing tachyzoites, followed by
encystations as bradyzoites. Life cycle is completed when cat ingest tissues
of intermediate hosts containing bradyzoites. Human can become infected
postnatal by contact with oocyst from cat feces or consumption of
parasite in undercooked meat from infected animal like sheep or pig
(2-3).
In humans toxoplasma is also amongst commonest infections to be transmitted during
pregnancy. Mothers who are infected during pregnancy have on average 30 percent
chance of infecting their fetus. More so in last trimester
(60%) than first (14%) and second (29%). (4).

Methods

In order to examine the relation between toxoplasmosis and psychiatric disorders, PsycINFO and MEDLINE searches were conducted. Search terms included: toxoplasmosis, toxoplasmosis and psychiatry. Case reports and review articles were critically appraised. Further references were obtained from identified articles

Results

Extensive literature review revealed ample evidence linking toxoplasma infection to
major psychiatric conditions.


The following findings were found to be of special significance-
(1).Studies done on mothers of schizophrenics have persistently shown elevated
titers of IgM against T. gondii (5-6).
(2).Between 1953 and 2003, 18 out of 19 studies show individuals with serious
psychiatric problems (inpatients) to have increase level of antibody to
T.gondii and 11 of these studies showed difference being statistically
significant. (7)
(3).Leweke et al., 2004, (8) investigated the levels of toxoplasma antibodies in serum and CSF (cerebrospinal fluid) of patients with schizophrenia. They found untreated individuals with recent onset of schizophrenia had higher level. Treatment resulted in decrease level.
(4).Toxoplasma infection in AIDS patients has been found to result in delusions,
hallucinations and thought disorder. (9).
(5).Significant changes in personality and psychomotor performance have
been found in asymptomatic toxoplasma positive individuals. (10-12).
And these changes in personality and psychomotor performance seems to be
directly proportional to level of anti- toxoplasma immunity. (10-11)
(6).Several medications like valproic acid and haloperidol used in psychiatric
disorders have the ability to inhibit the in vitro replication of T. gondii. (13).
(7).Selten and Kahn, 2002(14) did a 30-year follow up study of 13
persons known to have congenital toxoplasmosis. (asymptomatic at birth).
Five subjects refuse to collaborate, five remain healthy, and one committed suicide
(Diagnosed as antisocial personality), one had major depression
with cannabis dependence and another one had gender identity disorder. So
out of 8 who could be followed up 3 developed significant psychiatric
problems.
(8).Increase in dopamine level can play a role in many forms of schizophrenia.
(15-17). It has been demonstrated that toxoplasma infection results in increase level of dopamine in mice. (18)
(9).Nitric oxide serves as one of neurotransmitter in brain, which can be
neurotoxic in high dose. It has been found to be elevated in both schizophrenia as well
toxoplasma positive individuals. (19). Research supports nitric oxide
role as anti-infective agent in brain especially against toxoplasma. (20). But vigorous high levels as found in toxoplasma infection might be resulting in neuronal damage (21).
(10).T. gondii cysts lie within the cells of Para ventricular region of the human brain and congenital infection has been found to result in necrosis along lateral ventricles. This necrosis of cells results in loss of cell lining of ventricles as well blockage of
cerebral aqueduct, which leads to swelling of lateral ventricles. This swelling resembles the ventricular enlargement seen in Schizophrenia and bipolar disorders. (22)
(11).France and Ireland which has a higher prevalence of schizophrenia also has
much higher incidence of Toxoplasma gondii (7).

DISCUSSION

We know humans like mice are intermediate hosts in life cycle.
Parasite species are known to influence the behavior of their host to
increase their probability to move to new host and complete their life cycle.
Behavior alteration is meant to increase intermediate host susceptibility
to predation and therefore the probability of their transmission to a definitive
host. (23). Toxoplasma achieves its objective probably by increasing synthesis
of dopamine (18), or by secreting‘LSD’ like substance (linked to serotonin)
(22). And interestingly they are the same neurotransmitters, which
are affected, in most of psychiatric conditions (15).
Infected rodents have been observed to show adverse behavior, which make them easy prey for cats. Some of the behavior changes observed during trials have included impaired motor performance and higher activity level (24), deficits in
learning capacity and memory (25), longer reaction time (26), and reduced specific predator avoidance (27).
What we are suggesting here is that when humans enter the life cycle of toxoplasma gondii and get infected. It is possible that neurotransmitter induced behavioral changes results in psychiatric conditions. This hypothesis is supported by many studies, which prove the personality-altering role of toxoplasma gondii in humans. (10-12, 28, 29)
J.Flegr et al, 2003(10) did a study on 857 military conscripts and found
toxoplasma positive subjects mostly had just elementary education,
significantly lower verbal intelligence and significantly lower factor of
novelty seeking. Other studies on humans with latent toxoplasmosis
have also shown significant impaired psychomotor performance and prolonged
reaction time in the subjects (29-30).
Question arises why only a few toxoplasma gondii positive individuals suffer from
psychiatric problems? Possible explanation could be in genetic variation, which seems to
play decisive role to confer vulnerability to pathogen like T.gondii. (31-32)

Conclusion

Hypotheses of “infectious causation of psychiatric disorders” should be active focus of research. And establishing role of toxoplasma gondii in etiopathogenesis in many psychiatric disorders might lead to new medication for their prevention and treatment.

References-

 

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