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Influence of latent Toxoplasma infection on human personality, physiology and morphology: Pros and cons of the Toxoplasma-human model in studying the manipulation hypothesis


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The parasitic protozoan Toxoplasma gondii infects about one-third of the population of developed countries. The life-long presence of dormant stages of this parasite in the brain and muscular tissues of infected humans is usually considered asymptomatic from the clinical point of view. In the past 20 years, research performed mostly on military personnel, university students, pregnant women and blood donors has shown that this 'asymptomatic' disease has a large influence on various aspects of human life. Toxoplasma-infected subjects differ from uninfected controls in the personality profile estimated with two versions of Cattell's 16PF, Cloninger's TCI and Big Five questionnaires. Most of these differences increase with the length of time since the onset of infection, suggesting that Toxoplasma influences human personality rather than human personality influencing the probability of infection. Toxoplasmosis increases the reaction time of infected subjects, which can explain the increased probability of traffic accidents in infected subjects reported in three retrospective and one very large prospective case-control study. Latent toxoplasmosis is associated with immunosuppression, which might explain the increased probability of giving birth to a boy in Toxoplasma-infected women and also the extremely high prevalence of toxoplasmosis in mothers of children with Down syndrome. Toxoplasma-infected male students are about 3 cm taller than Toxoplasma-free subjects and their faces are rated by women as more masculine and dominant. These differences may be caused by an increased concentration of testosterone. Toxoplasma also appears to be involved in the initiation of more severe forms of schizophrenia. At least 40 studies confirmed an increased prevalence of toxoplasmosis among schizophrenic patients. Toxoplasma-infected schizophrenic patients differ from Toxoplasma-free schizophrenic patients by brain anatomy and by a higher intensity of the positive symptoms of the disease. Finally, five independent studies performed in blood donors, pregnant women and military personnel showed that RhD blood group positivity, especially in RhD heterozygotes, protects infected subjects against various effects of latent toxoplasmosis, such as the prolongation of reaction times, an increased risk of traffic accidents and excessive pregnancy weight gain. The modern human is not a natural host of Toxoplasma. Therefore, it can only be speculated which of the observed effects of latent toxoplasmosis are the result of the manipulation activity of the Toxoplasma aimed to increase the probability of its transmission from a natural intermediate to the definitive host by predation, and which are just side effects of chronic infection.
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Toxoplasma as the model organism for studying the parasite
manipulation hypothesis
Toxoplasma gondii is a parasitic protozoan whose effects on human
behaviour, personality and other phenotypic traits have been
studied most thoroughly, often in the context of the manipulation
theory, the theory suggesting that many parasites change the
phenotype of their host to increase their chances of transmission to
a new host by, for example, predation. There are various reasons
why this particular protozoon has become a favoured model for
evolutionary parasitologists, biologists and also psychiatrists.
First of all, Toxoplasma is a very common parasite both in
developed and developing countries, and some forms of diseases
caused by Toxoplasma infection have very serious impacts on
human health; taken together, all forms of toxoplasmosis are a
serious socio-economic burdens throughout the world (Pappas et
al., 2009; Torgerson and Macpherson, 2011). It is also important
to note that the study of the influence of toxoplasmosis on the
behaviour of laboratory animals has a very long tradition; this
includes a series of about 20 studies that started in the laboratory
of William M. Hudtchison in the early 1980s, followed by studies
by Joanne P. Webster and Manuel Berdoy in the 1990s, which were
succeeded by several other teams (for reviews, see Skallová et al.,
2006; Webster, 2007; Webster and McConkey, 2010).
Toxoplasma is an excellent model for studying the manipulation
hypothesis as it is trophically transmitted from an intermediate to a
definitive host by predation. In contrast to behavioural patterns
induced by directly or, more commonly, sexually transmitted
parasites, the behavioural patterns induced by a trophically
transmitted parasite are relatively easy to recognize (Parker et al.,
2009). For example, in a sexually transmitted parasite, the parasite’s
and the host’s genes have similar interests: they both ‘try’ to program
the host to increase the probability of host reproduction. In contrast,
the interests of the host and its trophically transmitted parasite
radically differ. The intermediate host, e.g. the mouse, needs to
survive (and reproduce) for as long as possible while the parasite,
e.g. Toxoplasma, ‘wants’ the definitive host (here, a cat) to kill and
The parasitic protozoan Toxoplasma gondii infects about one-third of the population of developed countries. The life-long
presence of dormant stages of this parasite in the brain and muscular tissues of infected humans is usually considered
asymptomatic from the clinical point of view. In the past 20years, research performed mostly on military personnel, university
students, pregnant women and blood donors has shown that this ʻasymptomaticʼ disease has a large influence on various
aspects of human life. Toxoplasma-infected subjects differ from uninfected controls in the personality profile estimated with two
versions of Cattellʼs 16PF, Cloningerʼs TCI and Big Five questionnaires. Most of these differences increase with the length of time
since the onset of infection, suggesting that Toxoplasma influences human personality rather than human personality influencing
the probability of infection. Toxoplasmosis increases the reaction time of infected subjects, which can explain the increased
probability of traffic accidents in infected subjects reported in three retrospective and one very large prospective case-control
study. Latent toxoplasmosis is associated with immunosuppression, which might explain the increased probability of giving birth
to a boy in Toxoplasma-infected women and also the extremely high prevalence of toxoplasmosis in mothers of children with
Down syndrome. Toxoplasma-infected male students are about 3cm taller than Toxoplasma-free subjects and their faces are
rated by women as more masculine and dominant. These differences may be caused by an increased concentration of
testosterone. Toxoplasma also appears to be involved in the initiation of more severe forms of schizophrenia. At least 40 studies
confirmed an increased prevalence of toxoplasmosis among schizophrenic patients. Toxoplasma-infected schizophrenic patients
differ from Toxoplasma-free schizophrenic patients by brain anatomy and by a higher intensity of the positive symptoms of the
disease. Finally, five independent studies performed in blood donors, pregnant women and military personnel showed that RhD
blood group positivity, especially in RhD heterozygotes, protects infected subjects against various effects of latent
toxoplasmosis, such as the prolongation of reaction times, an increased risk of traffic accidents and excessive pregnancy weight
gain. The modern human is not a natural host of Toxoplasma. Therefore, it can only be speculated which of the observed effects
of latent toxoplasmosis are the result of the manipulation activity of the Toxoplasma aimed to increase the probability of its
transmission from a natural intermediate to the definitive host by predation, and which are just side effects of chronic infection.
Key words: behaviour, parasite, polymorphism, Rhesus factor, personality questionnaire, toxoplasmosis.
Received 10 April 2012; Accepted 26 August 2012
The Journal of Experimental Biology 216, 127-133
© 2013. Published by The Company of Biologists Ltd
Influence of latent Toxoplasma infection on human personality, physiology and
morphology: pros and cons of the Toxoplasma–human model in studying the
manipulation hypothesis
Jaroslav Flegr
Faculty of Science, Charles University, Department of Philosophy and History of Science, Prague, Czech Republic
eat the infected intermediate host. Some toxoplasmosis-associated
behavioural changes, e.g. the prolongation of reaction times in the
infected hosts (Hrdá et al., 2000), are rather simple and therefore
difficult to recognize from the side effects of the parasitic disease.
Other changes, however, are relatively complex and specific, e.g. the
fatal attraction phenomenon, i.e. the loss of the fear response to cat
odour (and not, for example, to dog odour) in infected rodents
(Berdoy et al., 2000). The existence of such complex behavioural
patterns suggests that the observed toxoplasmosis-associated changes
are the products of the parasite’s manipulative activity rather than
side effects of the acute toxoplasmosis (Poulin, 1995). This is further
supported by the fact that the intensity of some of the observed
behavioural changes increases with the length of time since the onset
of infection (Flegr et al., 1996; Havlíček et al., 2001). If the observed
behavioural patterns were merely the side effects of the acute form
of infection, their intensity would decrease over time from the
moment of the infection.
The probable role of Toxoplasma gondii in the origin and progress
of some important psychiatric diseases, including schizophrenia, is
another reason why this protozoan has become the most important
model for studying the influence of a parasite on human behaviour.
Schizophrenia afflicts about 0.5–1% of the population in all countries
worldwide and its health and socioeconomic impacts are
extraordinary (Saha et al., 2005). Since the 1950s it has been known
that the prevalence of toxoplasmosis in schizophrenic patients is
unusually high (Torrey et al., 2007). This systematic research was
initiated and developed by Edwin F. Torrey from the Stanley
Research Institute and Robert H. Yolken from the Johns Hopkins
University, who showed that the connection between schizophrenia
and toxoplasmosis is very strong and that the Toxoplasma infection
is most probably a very significant (but not exclusive) cause of
schizophrenia (Torrey and Yolken, 1995; Torrey and Yolken, 2005).
The effect of latent toxoplasmosis on the risk of schizophrenia is
stronger than that of any schizophrenia-associated gene variant
identified in genome-wide analyses (The International Schizophrenia
Consortium, 2009). A prospective study performed on personnel of
the American Army revealed that specific anti-Toxoplasma
antibodies show up in the serum of subjects before they contract
schizophrenia (Niebuhr et al., 2007). It was shown later that
toxoplasmosis increases the concentration of dopamine in the brain
of infected hosts, including humans (Flegr et al., 2003), and its
genome even contains unique genes for enzymes (tyrosine
hydroxylases) that play an important role in the synthesis of
dopamine (Gaskell et al., 2009). The increased concentration of
dopamine in certain regions of the brain is believed to play a key role
in the origin and progress of schizophrenia and the inhibition of
dopamine receptors is the basis of the function of all modern drugs
used in the treatment of schizophrenia (Tandon et al., 2010). Other
studies have shown that the symptom profiles of Toxoplasma-
infected and Toxoplasma-free schizophrenia patients differ and the
positive symptoms of the disease (hallucinations, delusions) are more
severe in Toxoplasma-infected patients (Wang et al., 2006). Modern
imaging techniques revealed that the morphology of the brain of
schizophrenics differs from that of controls by having a lower density
of grey matter (GM) in certain parts of the brain (Shenton et al.,
2001). A magnetic resonance imaging (MRI) study published in 2011
showed that these differences (reduction of GM volume bilaterally
in the caudate, median cingulate, thalamus and occipital cortex, and
in the left cerebellar hemisphere) are observed only in Toxoplasma-
infected patients while Toxoplasma-free patients (as well as
Toxoplasma-infected controls) have the same brain morphology as
Toxoplasma-free controls (Horacek et al., 2012). This observation
suggests that toxoplasmosis can induce morphological changes in the
brain of genetically predisposed subjects, which, possibly together
with a toxoplasmosis-associated imbalance in the levels of dopamine
and other neurotransmitters, e.g. serotonin (Henriquez et al., 2009)
or nitric oxide (NO) (Kaňková et al., 2010a), can result in
Changes in the personality profile of humans with latent
The personality profile of Toxoplasma-infected subjects was
studied using three standard psychological questionnaires, i.e.
Cattell’s 16PF, Cloninger’s TCI, NEO-PI-R (Big Five), and one
special psychological questionnaire, Toxo94, that searched for
specific changes expected to occur in subjects infected by the
parasite transmitted from prey to predator (Flegr, 2007). Several
studies have shown that infected men exhibited lower scores on
Cattell’s factor G – superego strength (they have tendency to
disregard rules) and higher scores on Cattell’s factor L – protension
(they are more suspicious and jealous). In women, the shift in these
two factors is opposite to that of men; they mainly show a positive
shift in Cattell’s factor A – affectothymia (they are more warm-
hearted, outgoing and easy-going than the more reserved, detached
and critical Toxoplasma-free women). With a new version of
Cattell’s questionnaire (v. 5), the infected men showed increased,
rather than decreased, scores on superego strength [(Flegr, 2010b)
for an explanation of discordant results between studies, see chapter
4]. Cloninger’s TCI showed that infected subjects, both men and
women, have decreased scores on factor NS – novelty seeking, i.e.
a lower tendency to search for new stimuli (Flegr et al., 2003;
Skallová et al., 2005). Ethopharmacological studies have shown
that lower novelty seeking scores are characteristic for individuals
with an increased concentration of dopamine in the brain tissue,
which is in an agreement with the increased synthesis of dopamine
in tissue cysts of Toxoplasma found in the brain of infected hosts
and with results of ethopharmacological studies performed with
Toxoplasma-infected mice (Hodková et al., 2007; Skallová et al.,
2005). Some studies also suggest that infected subjects have higher
scores on Cloninger’s ST – self-transcendence (Novotná et al.,
2005; Skallová et al., 2005). The NEO-PI-R questionnaire showed
more extraversion in infected subjects, both men and women, and
less conscientiousness in comparison with Toxoplasma-free
subjects (Lindová et al., 2012).
On the basis of predictions of the manipulation theory and
introspection of the Toxoplasma-infected author, a special
questionnaire called Toxo94 was constructed (Flegr, 2010b). This
questionnaire consisting of only 10 questions was distributed to
several groups of subjects tested for toxoplasmosis, such as two
large groups of university students and a group of women screened
for toxoplasmosis during pregnancy (Flegr, 2010b). The results
showed that infected men more often reported that diplomacy is not
their strong point, that their instinctive (reflex) behaviour under
imminent danger is rather slow and passive, that they believe that
some people have the power to impose their will on others with
hypnosis or through other means and that when they are attacked,
physically or otherwise, or when they should fight for something
important, they stop fighting at a certain moment because their own
subconsciousness betrays them and they loss the will to fight back.
The infected women more often report that diplomacy is not their
strong point, that their instinctive (reflex) behaviour under
imminent danger is rather slow and passive, that they believe that
some people have the power to impose their will on others with
hypnosis or otherwise and that they have a weak instinct for self-
The Journal of Experimental Biology 216 (1)
129Toxoplasmosis and human behaviour
preservation: in situations where somebody else might be afraid,
for example being alone in a forest at night or in an empty house,
they remain calm.
Influence of latent toxoplasmosis on human behaviour
Toxoplasma-infected subjects have prolonged reaction times, as
measured by a test of simple reaction times (Havlíček et al., 2001).
The psychomotor performance gets worse with the level of
development of the infection (estimated on the basis of a decrease
in the concentration of specific anti-Toxoplasma antibodies). The
performance of the subjects in the 3min simple reaction time test
suggests that toxoplasmosis impairs long-term concentration ability
rather than maximum performance. The largest performance
decrease in the test occurred in RhD negative subjects while the
performance of RhD-positive heterozygotes was not influenced by
the infection (Flegr et al., 2010; Novotná et al., 2008). The impaired
psychomotor performance of infected subjects can explain the
higher risk of traffic accidents and work accidents observed in four
retrospective studies (Alvarado-Esquivel et al., 2012; Flegr et al.,
2002; Kocazeybek et al., 2009; Yereli et al., 2006) and one
prospective study (Flegr et al., 2009). The risk of traffic accident
is again increased in RhD-negative drivers (Flegr et al., 2009). A
double-blind observational study showed that Toxoplasma-infected
men scored lower in clothes tidiness than uninfected men, whereas
infected women scored higher (but not significantly so) than
uninfected women (Lindová et al., 2006). Similarly, infected men
scored lower and infected women scored higher in sociability.
These outcomes match the results of the personality questionnaires.
The infected rural male students scored higher in suspiciousness
while infected rural female students scored lower in suspiciousness
than their non-infected peers (Lindová et al., 2006), which again
agrees with the results obtained with Cattell’s 16PF questionnaire.
However, the very opposite was true for students of urban origin –
infected male students showed lower and infected female students
higher suspiciousness than their Toxoplasma-free peers. Using the
method of experimental games, it was shown that both infected men
and infected women were less altruistic than Toxoplasma-free
subjects in the Dictator game while in the Trust game, the infected
men were less altruistic and infected women were more altruistic
than Toxoplasma-free men or women (Lindová et al., 2010).
Influence of Toxoplasma on the human phenotype
In addition to its influence on personality profile and behaviour,
Toxoplasma is known to affect other phenotypic traits in humans.
For example, infected male university students (age 19–22years)
have increased concentrations of testosterone (Flegr et al., 2008a;
Flegr et al., 2008b) and, from photographs, their faces are rated as
more masculine and dominant by females (Hodková et al., 2007).
In contrast, infected female students have decreased levels of
testosterone – which corresponds to decreased levels of testosterone
in infected male and female mice (Kaňková et al., 2011). Infected
male students are 3cm taller than non-infected male students and
both male and female students have a lower index finger to ring
finger ratio (Flegr et al., 2005b), which is considered as an
indication of being exposed to higher concentrations of testosterone
during pregnancy (Manning, 2002). The increased concentration of
testosterone was also recently reported in Toxoplasma-infected
men, women (Shirbazou et al., 2011) and rats (Vyas, 2013). It
should be noted, however, that recent studies performed on two
independent populations did not find increased levels of
testosterone in infected male soldiers and immunology clinic
patients (see Table1). An alternative explanation for the observed
increase in the level of testosterone in males (and expected increase
in the level of oestrogen) was suggested by James (James, 2010).
He proposed that high testosterone and high oestrogen individuals
are more susceptible to any infection, including the Toxoplasma
infection. This model can explain the increased concentration of
testosterone in men; however, it cannot explain the increased
concentration of testosterone in laboratory-infected rodents.
The infected students differ from non-infected students in
various morphological traits; however, at least some of the
observed differences could be caused by differences between the
populations of students coming from towns and from villages
(where the prevalence of latent toxoplasmosis is much higher than
Table1. Concentration of steroid hormones in Toxoplasma-infected and Toxoplasma-free subjects
Men Women
Toxoplasma free Toxoplasma infected Toxoplasma free Toxoplasma infected
NMean s.d. NMean s.d. tPNMean S.D. NMean s.d. tP
Immunology clinic patients
Testosterone 26 15.16 5.99 12 14.40 4.11 –0.029 0.796 128 1.21 0.61 65 1.37 0.79 0.064 0.186
Cortisol 26 200.90 82.60 13 204.90 74.15 0.040 0.717 129 226.10 125.40 65 226.80 125.40 –0.021 0.661
Estradiol 26 0.0986 0.0417 13 0.1013 0.0309 0.066 0.556 129 0.2049 0.2537 65 0.2985 0.3811 0.066 0.169
Military personel
Testosterone 50 15.87 4.55 50 15.19 3.04 –0.032 0.526 46 1.49 0.53 47 1.52 657.40 –0.029 0.682
Cortisol 50 542.50 122.30 50 466.90 108.30 –0.269 0.000 46 712.80 365.80 47 741.90 342.70 0.039 0.578
Estradiol 50 0.1146 0.0271 50 0.1123 30.70 –0.091 0.178 46 0.2883 0.3457 47 0.3009 0.3416 0.028 0.687
Students 2003–2006
Testosterone 1 68 0.393 0.234 22 0.496 0.251 0.161 0.026 143 0.272 0.274 29 0.252 0.400 –0.282 0.007
Testosterone 2 68 0.349 0.242 21 0.428 0.219 0.152 0.035 133 0.272 0.248 28 0.230 0.379 –0.142 0.003
Students 2007–2010
Testosterone 1 64 0.776 0.845 9 0.840 0.707 0.116 0.148 148 0.361 0.505 22 0.738 1.165 –0.186 0.000
Testosterone 2 63 0.561 0.645 8 0.489 0.222 0.060 0.461 155 0.186 0.136 24 0.176 0.115 –0.241 0.000
Cortisol 1 67 4.820 3.538 9 5.003 4.306 0.013 0.868 148 5.456 3.322 25 4.177 3.983 –0.137 0.007
Cortisol 2 67 3.049 1.630 9 2.040 1.236 –0.197 0.013 149 2.929 1.586 24 3.118 2.434 0.030 0.559
The concentration (nmoll–1) of total hormones was determined in serum of immunology patients and military personal, and that of free hormones was
determined in saliva of university students. Two samples were collected, the first at 09:00h (before ethological and psychological testing of students) and the
second at 11:30h. Statistical significance of the effect of toxoplasmosis on hormone concentration was estimated with a partial Kendall test, with age of
subjects as covariate. Significant results are shown in bold. (J.F., Š. Kaňková, M. Bičíková and J. Klose, unpublished.)
in Prague) (Kodym et al., 2000). Infected pregnant women have an
increased probability of giving birth to a boy; the shift in the sex
ratio is especially high in women with relatively recent latent
infection. The women with high levels of anti-Toxoplasma IgG
antibodies (but with low levels of IgM antibodies) gave birth to 250
boys per 100 girls while the women with low levels of anti-
Toxoplasma IgG antibodies gave birth to more girls than boys
(Kaňková et al., 2007b). The same effects have been confirmed in
mice infected with Toxoplasma in the laboratory (Kaňková et al.,
2007a). Pregnant women with toxoplasmosis have increased
weight gain: in the subpopulation of RhD-negative Toxoplasma-
infected women, the weight gain was nearly twice as high in the
16th week of pregnancy as in other pregnant women (Kaňková et
al., 2010b). The rate of early fetal development is lower and the
length of pregnancy is about 1.5days longer in Toxoplasma-
infected than in non-infected mothers (Flegr et al., 2005a; Kaňková
et al., 2010b). The children of Toxoplasma-infected mothers have
lower rates of motor development in the first 18months of life
(Kaňková et al., 2012). Most differences in the reproduction-
associated traits between infected and non-infected women can be
explained as being a result of immunosuppression and the resulting
(expected) decrease in the stringency of embryo quality control
(Neuhäuser and Krackow, 2007), which has been observed in both
humans (Flegr and Stříž, 2011) and mice (Kaňková et al., 2010a)
with latent toxoplasmosis. A large proportion of embryos with
various developmental defects, as well as a large percentage of
more immunogenic male embryos, are aborted in the early weeks
of pregnancy. In immunosuppressed Toxoplasma-infected women,
a fraction of such embryos are saved. This phenomenon can explain
not only the decreased rates of prenatal and postnatal development
of children of infected mothers but also the increased sex ratio in
their offspring. The lower stringency of embryo quality control can
also explain the observation published in the early 1960s of a
dramatically higher prevalence of toxoplasmosis in mothers of
children with Down syndrome, 84% versus 32% in controls
(Hostomská et al., 1957).
An endocrine hypothesis for the increased sex ratio of recently
infected women and decreased sex ratio of women infected for a long
time – namely, originally (before the infection) higher oestrogen and
testosterone levels in Toxoplasma infection-sensitive subjects and a
reduced concentration of these hormones as consequence of long-
term infection – has also been suggested (James, 2008; James, 2010).
The increased sex ratio of recently infected women can also be
explained by Catalano’s stress hypothesis, i.e. selective abortion of
male embryos of chronically stressed women (Catalano et al., 2012).
It should be noted that the immunological and the endocrine or stress
hypotheses are compatible as the increased level of steroids is known
to impair the function of the immune system.
An analogous effect to the fatal attraction phenomenon (Berdoy
et al., 2000; Kannan et al., 2010; Webster and McConkey, 2010)
was observed in Toxoplasma-infected humans. Infected men rated
the smell of cat urine as relatively more pleasant while infected
women rated it as relatively less pleasant compared with non-
infected controls (Flegr et al., 2011). Using urine from four other
animal species (tiger, dog, horse, brown hyena), a similar but
weaker effect was observed for hyena urine. Like the cat, the hyena
is a member of the Feliformia suborder; however, it is not known
whether any representatives of this superfamily other than cats
(family Felinidae) can be definitive hosts of Toxoplasma. The fatal
attraction phenomenon was not observed with tiger urine. This is
rather surprising because large cats are definitive hosts of
Toxoplasma, and monkeys and apes are a regular component of
their prey. It may be that the difference in the effects of the smell
of cat and tiger urine on human behaviour is due to the fact that the
important pheromone felinine is present in the urine of small cats
(Felinae subfamily) but absent in the urine of large cats
(Pantherinae subfamily) (Hendriks et al., 1995). It is, however,
possible that chance strongly influences which of the urine samples
is active in the fatal attraction test. In our study (Flegr et al., 2011),
samples of five individuals of each species were used in smell-
rating experiments. However, the relative attractiveness of
particular samples can still depend on the sample concentration and
the time elapsed from sample collection. It has been observed that
the effect of toxoplasmosis on olfactory preference follows an
inverted-Ufunction – the effect on mice is not observed when using
either a high or a very low amount of cat urine (Vyas et al., 2007).
Therefore, the results of odour studies partly depend on the dilution
of the samples tested. In this context, interesting side results were
obtained in one of our evolutionary psychology studies run in
parallel with the fatal attraction study. We found that the smell of
urine of men and of women in the fertile phase of the menstrual
cycle was relatively more pleasant for Toxoplasma-infected male
raters (Fig.1). No significant effect of toxoplasmosis was observed
with urine of women in infertile phases of the menstrual cycle. It
is possible that the smell of strange male urine might signal a
potential danger, which is not avoided to the same extent by
infected men – as has been suggested in a similar context by the
stress-coping hypothesis (Lindová et al., 2010).
Advantages and disadvantages of the Toxoplasma–human
model for studying the manipulation hypothesis
The greatest advantage of the Toxoplasma-human model for
studying the manipulation hypothesis is the convenience of
obtaining empirical data. Practically any clinical, ethological,
anthropological or psychological study could be supplemented with
testing the experimental subject for the presence of anamnestic anti-
Toxoplasma antibodies and with the comparison of the data from
Toxoplasma-infected and Toxoplasma-free subjects. Moreover, all
pregnant women are being screened for toxoplasmosis in some
countries. Here, we could just ask the women tested to provide
informed consent for the use of their clinical data or to complete a
special, e.g. psychological, questionnaire.
The human is a long-living animal, especially in contrast with
laboratory rodents. This is another very important advantage in
manipulation hypothesis studies (but see Webster et al., 2013). Acute
toxoplasmosis is usually only a mild disease in humans, a short event
in a long human life. The life-long latent toxoplasmosis is mostly
considered asymptomatic from the clinical point of view. Therefore,
there is little risk of mistaking manifestations of Toxoplasma’s
manipulative activity for side effects of the parasitic disease suffered.
The possible side effects of acute infection can be identified by
searching for a positive or negative correlation between the time
elapsed from the infection (which can be derived from the patient
medical records or estimated from the concentration of anamnestic
antibodies) and the intensity of the observed Toxoplasma-associated
phenotypic changes. Of course, the existence of such a positive
correlation cannot distinguish whether the observed changes are
manifestations of the manipulative activity or only symptoms of the
chronic disease. In the case of human parasites, we cannot run a
predation study, i.e. we cannot tell whether the manipulation activity
objectively increases the efficiency of parasite transmission from
intermediate to definitive host by comparing the prevalence of the
parasite in intermediate hosts captured and eaten by the definitive
host with that in a population of the intermediate host living in the
The Journal of Experimental Biology 216 (1)
131Toxoplasmosis and human behaviour
same area. Theoretically, it would be possible to compare the
intensity of behavioural manifestations of toxoplasmosis in high-
prevalence areas (with high rates of superinfections, i.e. new
infections in hosts previously infected with Toxoplasma) with the
intensity in low-prevalence areas (where the rates of superinfections
are low). The virulence of non-manipulative parasites increases in
the high-prevalence areas because in the competition between
different genetic lines of the parasite in the body of a superinfected
host, the winners are the lines with the highest rates of reproduction
and therefore usually those with the highest virulence (Ewald, 1994).
In contrast, the virulence of manipulative parasites decreases in the
high-prevalence areas, because in the competition within the body of
an infected host, the winners are the lines of non-manipulators that,
instead of wasting resources in the manipulation activity, invest the
maximum resources in reproduction (and leave the manipulation to
their competitors). Such studies, however, should be performed in a
long-term stable area and it is clear that the human is not a suitable
model. Even studies conducted in some suitable model animal in a
stable environment would not differentiate between the direct and
indirect manipulation activity. It is highly probable that some of the
observed effects, for example the shift of the sex ratio in infected
humans and mice (Kaňková et al., 2007a; Kaňková et al., 2007b),
are only side effects of the manipulative activity of Toxoplasma,
primarily aimed at suppressing the activity of the immune system of
the infected host and therefore increasing the survival of the parasite
in the host organism.
For obvious reasons, a laboratory infection experiment using a
Toxoplasma–human model to study the manipulation hypothesis is
not feasible. This is an important obstacle to the study of the causal
relationship between Toxoplasma infection and various
toxoplasmosis-associated traits. For example, the lower NEO PI-R
conscientiousness in infected subjects (Lindová et al., 2012) could
be an effect of the infection or it may be that there is a higher
probability of infection in persons with lower conscientiousness who
may have a lower tendency to adhere to hygienic standards. In some
cases, the causality direction is quite obvious. It is more probable that
toxoplasmosis causes impairment of reaction times than the persons
with longer reaction times having a higher probability of infection.
Sometimes, a longitudinal study can help; however, a large number
of subjects, preferably several thousand, would be needed for such a
study when the incidence of the parasitosis is relatively low. Before
the presence of genes for dopamine-synthesizing enzymes in the
genome of Toxoplasma was revealed (Gaskell et al., 2009) and
before an increased dopamine synthesis rate was found in
Toxoplasma tissue cysts (Prandovszky et al., 2011), it was not
possible to decide whether the positive association between
toxoplasmosis and schizophrenia was more probably caused by the
effect of Toxoplasma on the brain of predisposed individuals or by
a higher risk of Toxoplasma infection in schizophrenics. The results
of a prospective longitudinal study performed on US army personnel,
however, showed that Toxoplasma infection often precedes the first
episode of schizophrenia (Niebuhr et al., 2008).
An important hint concerning the causality can be provided by
measurement of the correlation between the duration of Toxoplasma
infection and the amount of observed phenotypic change. The
existence of a positive correlation suggests that the difference
observed between the infected and non-infected subjects is probably
the effect of latent infection. A negative correlation suggests that the
difference is a fading-out effect of past acute infection and the
absence of any correlation is likely to indicate that subjects with a
particular phenotype have an increased risk of infection. The
published results of similar studies suggest that many statistical
associations between latent toxoplasmosis and phenotypic traits are
caused by the effect of toxoplasmosis on the host phenotype;
however, some associations are probably caused by the effect of a
particular trait on the risk of infection and certain associations by
parallel effects of some third, known or unknown, factor on the host
phenotype and on the risk of Toxoplasma infection.
The last but yet very serious disadvantage of the human model is
connected with extreme genetic polymorphism in the human
population as well as with extreme heterogeneity of the
environmental factors that affect individuals in the study population.
Such genetic and non-genetic heterogeneity has a strong negative
influence on the observed effect size of any factor studied, including
latent toxoplasmosis. In statistics, the effect size is often estimated
as the proportion of the total variability of a dependent variable (e.g.
Non-infected Infected Non-infected Infected
Women Men
Fertile women
Non-fertile women
Odour pleasantness score
Fig.1. Differences between Toxoplasma-infected
and Toxoplasma-free men and women in the
odour pleasantness scores attributed to urine
samples of men, fertile and non-fertile women,
and cats. The signs denote the mean raw scores
attributed by a particular population to the
samples tested (at least five samples from
different individuals of the same species were
used); the vertical bars denote 0.95 confidence
intervals. Higher scores were attributed to urine
samples with a more pleasant smell (in
comparison with other urine samples). The
statistical significance of the toxoplasmosis–sex
interaction for men, women in the fertile phase of
the menstrual cycle, women in the non-fertile
phase of the menstrual cycle and cats was 0.021,
0.021, 0.067 and 0.006, respectively. The urine
odour was rated by 36 Toxoplasma-free women,
9 Toxoplasma-infected women, 26 Toxoplasma-
free men and 7 Toxoplasma-infected men on a 7-
point scale. (J.F., P. Lenochová, Z. Hodný and M.
Vondrová, unpublished.)
of a personality factor) that can be explained by the independent
variable studied (e.g. toxoplasmosis). While in studies performed on
inbred laboratory animals or on F1 hybrids we can often see factors
explaining a high percentage of the total variability of a particular
behavioural variable, in ecological and evolutionary studies
performed on outbreeding organisms, we mostly see factors
explaining 2–7% of variability (Moller and Jennions, 2002);
therefore, to find significant effects, we may need to use an order of
magnitude larger samples than in inbred animal studies.
A large within-sample and between-samples variability of
human populations is also the cause of the fact that various studies
performed on different populations often provide different, even
opposite, results. In laboratory experiments on inbred animals, we
study genetically identical animals that have been exposed to very
similar environmental factors during their lives. Therefore, they
will probably react identically to the same factor, for example to
Toxoplasma infection. In humans, the situation is very different for
various reasons. For example, toxoplasmosis influences the human
body and mind through several independent pathways. Infected
men have a higher concentration of testosterone (Flegr et al., 2008a)
and, therefore, are likely to be more competitive, but at the same
time they have impaired reaction times (Havlíček et al., 2001).
Therefore, if in one study a self-administered simple reaction time
test is distributed to groups of 20 draftees during regular military
testing while in another study the same test is individually
administered by an attractive female PhD student to male university
students, it can be expected that in the first study, the negative
influence of toxoplasmosis on reaction times will prevail while in
the second, the higher competitiveness of the infected students will
prevail in the final effect (Flegr et al., 2008c). In both studies, we
would find a significant effect of toxoplasmosis on performance in
the test; however, in the first study the effect would be negative but
in the second it would be positive.
Most physiological processes are regulated on various levels, from
the molecular to the psychological. If, for example, Toxoplasma
causes an increase in the dopamine concentration in certain regions
of the brain, the dopamine-synthesizing cells in other areas of the
brain may degenerate. Therefore, at a certain stage of infection, we
can detect, paradoxically, a decreased, rather than an increased, level
of dopamine in the brain of infected individuals. If toxoplasmosis
induces a decrease in superego strength, it could increase the
tendency of certain individuals to lie while filling out a questionnaire
and therefore we could detect seemingly increased rather than
decreased superego strength in these subjects in questionnaire
studies. When a subject recognizes some personality change that
he/she does not like, for example a toxoplasmosis-associated increase
of extraversion, he/she may try, consciously or unconsciously, to
mask this change while completing the questionnaire and he/she can
even overcompensate for the real personality change by moving from
extraversion to introversion.
Some biological theories suggest that a large part of the genetic
polymorphism is sustained in a natural outbreeding population as
a result of epistatic interactions and frequency-dependent selection
(Flegr, 2010a; Mayr, 1963; Templeton, 2008). The particular alleles
cannot be fixed or eliminated from the population because they
increase a trait positively in the context of one genotype and
negatively in the context of another, or because they are
advantageous when rare and disadvantageous when common. The
population cannot get rid of various mutations by selection and
remains polymorphic, and its members react to the same stimuli in
different, often even opposite, ways. This affects the results of our
ethological and psychological studies. Toxoplasmosis quite often
influences the same personality factor in different populations (men
and women, rural and urban populations, or RhD-positive and
RhD-negative subjects); however, the direction of the effect of a
factor may vary between populations. When we study the effect of
a factor on a heterogeneous population, we often find a significant
increase of variance in certain dependent variables, rather than a
significant difference between the population means of particular
variables (see Poulin, 2013). For example, comparison of Cattell’s
16PF personality profiles of young women screened for
toxoplasmosis during pregnancy showed that infected females
scored higher in intelligence and lower in guilt proneness than
Toxoplasma-free females. At the same time, they differed in the
variance of four other personality factors, namely surgency,
protension, shrewdness and self-sentiment integration (Flegr and
Havlíček, 1999). In technical articles, tests for equality of variance
are commonly used only to check preconditions of the statistical
tests. Our experience with real data and the present knowledge of
the genetic architecture of phenotypic characters, however, suggest
that many genetic and environmental factors influence the variance
rather than the mean values of particular characters in polymorphic
populations. Therefore, the results of the tests for equality of
variance should be published as full-bodied results of such studies.
There are several objective reasons why Toxoplasma gondii is
now used as the most important model for studying manipulative
activity in humans, which are summarized in the first paragraphs
of the present article. However, the most important are subjective
reasons and also chance. A large number of parasitic organisms
probably exist in helminths, protozoa, fungi, bacteria, archea and
viruses that may influence the phenotype of their human host even
more than the Toxoplasma. These organisms are, however, still
waiting for research teams to engage in a systematic study of their
influence on the human host.
I would like to thank the organizers and all participants of The Journal of
Experimental Biology 2012 symposium ʻNeural parasitology: how parasites
manipulate host behaviourʼ for creating a friendly environment for stimulating
This study was supported by the Grand Agency of the Czech Republic [grant no.
P303/11/1398] and Charles University of Prague [grant no. UNCE 204004].
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... Toxoplasmosis is a parasitic disorder activated by T. gondii [18]. The disease affects over one-third of the human population globally [15]. The main carriers of T. gondii are cats (Felis catus) [8], though other animals like cattle, swine, sheep, goats, dogs, birds, etc. are potential reservoirs of the disease, T. gondii reservoirs can be categorized into two-living and non-living reservoirs. ...
... The main carriers of T. gondii are cats (Felis catus) [8], though other animals like cattle, swine, sheep, goats, dogs, birds, etc. are potential reservoirs of the disease, T. gondii reservoirs can be categorized into two-living and non-living reservoirs. Living reservoirs include cats (final hosts) and other animals (intermediate hosts) [21] while non-living reservoirs include contaminated water and soil [15]. It should be noted that unlike other reservoirs of T. gondii, cats remain asymptomatic throughout their life. ...
Full-text available
Toxoplasmosis is a parasitic disease instigated by T. gondii. T. gondii can infect every warm[1]blooded vertebrate and the proportion of the world population that is suffering from the parasitic disease is over one-third. In this work, a nonlinear epidemic model is developed to analyze how various factors can instigate backward bifurcation phenomenon in the transmission dynamics of toxoplasmosis. The model is subjected to the usability test by employing ample mathematical techniques and is found to be usable. An analytical threshold that governed T. gondii transmissibility is derived and used to study the model qualitatively. Results from the analysis establish the existence of backward bifurcation for toxoplasmosis dynamics.
... Modes of infection include ingestion of tissue cysts which might be present in undercooked meat or dairy products or ingestion of oocysts in unwashed vegetables and fruits. Organ transplantation and blood transfusion have also been reported as potential portals for parasite entry (Flegr, 2013). In addition, congenital toxoplasmosis is caused by the transplacental transmission of tachyzoites (Alharbi et al, 2017). ...
... samples with less variability than is found in the general population) increases the likelihood of finding even weak significant effects if they exist. On the other hand, this setup could also artificially increase or decrease the observed strength of detected effects (the amount of variability in an output variable explained by the factors under study) [49]. In short, due to the specific composition of the population of study participants, we must be careful with the generalization of the findings. ...
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The confirmed number of SARS-CoV-2 infections up to 18 October 2022 is 626 million worldwide, but information about factors affecting the probability of infection or a severe course of COVID-19 remains insufficient and often speculative. Only a small number of factors have been rigorously examined, mostly by retrospective or cross-sectional studies. We ran a preregistered study on 5164 Internet users who shared information with us about their exposure to 105 risk factors and reported being COVID-19 negative before the beginning of the fourth wave of COVID-19 in the Czech Republic. After the fourth wave, in which 709 (13.7%) of participants were infected, we used a partial Kendall test controlled for sex, age, and urbanization to compare the risk of infection and a severe course of the disease in subjects who initially did and did not report exposure to particular risk factors. After the correction for multiple tests, we identified 13 factors – including male sex, lower age, blood group B, and larger household size – that increased the risk of infection and 16 factors – including mask-wearing, borreliosis in the past, use of vitamin D supplements, or rooibos drinking – that decreased it. We also identified 23 factors that increased the risk of a severe course of COVID-19 and 12 factors that decreased the risk. This preregistered longitudinal study is of explorative nature. Therefore, although the observed effects were strong and remained highly significant even after correction for multiple tests, it will be necessary to confirm their existence in future independent studies.
... Toxoplasma gondii causes chronic infections characterized by the life-long presence of cysts in various tissues, including the CNS. In immunocompetent hosts, the infection is clinically asymptomatic, but behavioral alterations have been linked with latent toxoplasmosis [148,149]. While Kusbeci and colleagues reported higher T. gondii seropositivity among AD patients [150], other studies failed to confirm toxoplasmosis as a risk factor for AD [151,152] or general cognitive decline [153]. ...
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The amyloid cascade hypothesis, focusing on pathological proteins aggregation, has so far failed to uncover the root cause of Alzheimer’s disease (AD), or to provide an effective therapy. This traditional paradigm essentially explains a mechanism involved in the development of sporadic AD rather than its cause. The failure of an overwhelming majority of clinical studies (99.6%) demonstrates that a breakthrough in therapy would be difficult if not impossible without understanding the etiology of AD. It becomes more and more apparent that the AD pathology might originate from brain infection. In this review, we discuss a potential role of bacteria, viruses, fungi, and eukaryotic parasites as triggers of AD pathology. We show evidence from the current literature that amyloid beta, traditionally viewed as pathological, actually acts as an antimicrobial peptide, protecting the brain against pathogens. However, in case of a prolonged or excessive activation of a senescent immune system, amyloid beta accumulation and aggregation becomes damaging and supports runaway neurodegenerative processes in AD. This is paralleled by the recent study by Alam and colleagues (2022) who showed that alpha-synuclein, the protein accumulating in synucleinopathies, also plays a critical physiological role in immune reactions and inflammation, showing an unforeseen link between the 2 unrelated classes of neurodegenerative disorders. The multiplication of the amyloid precursor protein gene, recently described by Lee and collegues (2018), and possible reactivation of human endogenous retroviruses by pathogens fits well into the same picture. We discuss these new findings from the viewpoint of the infection hypothesis of AD and offer suggestions for future research.
... Penularan penyakit dapat terjadi antara hospes satu ke hospes lainnya, maupun dari hospes intermedier ke hospes definitif atau sebaliknya (Andreletti et al., 2007).Penularan dapat terjadi secara kongenital lewat plasenta, dari induk ke anak sewaktu dalam kandungan dan dapat setelah lahir (Tenter et al., 2000). Selain itu, penularan dapat melalui kontak langsung dengan protozoa obligate intraseluler melalui ingesti makanan atau minuman yang terkontaminasi oleh feses yang mengandung oosista, ingesti daging yang mengandung sista karena proses pemasakan yang tidak matang, transfusi darah dan transplantasi organ (Flegr, 2013;Henriquez et al., 2009;Jones and Dubey, 2012;Torrey and Yolken, 2013). Pada umumnya induk tidak menunjukkan gejala toksoplasmosis tetapi menularkan parasit ke anak (Taila et al., 2011). ...
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Toxoplasmosis is a zoonotic parasites caused by Toxoplasma gondii. The red fruit’s extract contains tocopherol and betacarotene as antioxidant and it can repair the bodies immune system. This research was aimed to study the effect of red fruit’s extract to erithrocytes, hemoglobine, the values of PCV and TPP concentration of mice infected with T. gondii, so that the red fruit extract can be used as alternative herbal medicine for eliminating Toxoplasmosis. 15 of Balb/C mice, male, three months, 30 gr of body weight were used as experimental animals. The mice were then devided into three groups. Group I was a control, group II was tachyzoite infected and group III was tachyzoite infected and given red fruit’s extract. Group III given red fruit’s extract on first day with 0,53 g/kg BW/mice/day. Mice in group II and III were infected by injection Toxoplasma gondii tachyziote 1x103 a mice intraperitoneally. The blood sample was taken from five mice in each group at 7th and 12th day pass through cantus medialis. The blood was examinated in Clinical Pathology Laboratory, Faculty of Veterinary Medicine, Gadjah Mada University. Data were analyzed by using Factorial 2 x 3. The result showed no significant difference (P>0,05) in hemoglobin, and PCV’s value between groups I, II and III before and after infection of T. gondii’s tachyzoite. The TPP’s value between groups I, II and III before and after infection of T. gondii’s tachyzoite was significantly difference (P<0,05).
... In later studies, using Cloninger's TCI personality tests, Toxoplasma-infected individuals demonstrated decreased scores on factor NS (novelty seeking). This means that individuals had a lower tendency to search for new stimuli, which was seen in both men and women [24][25][26]. Decreased novelty-seeking scores have been associated with increased concentration of dopamine in the brain tissue, which is consistent with the increased levels of dopamine since in the brain tissue of infected mice [25,27]. ...
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Toxoplasma gondii is a parasite that affects about 20–80% of the global population. Chronic infection with toxoplasma, also called latent infection, has largely been considered to be asymptomatic with minimal to no clinical effects or sequelae. Though there is now clear evidence in animal models and mounting evidence in humans that latent toxoplasmosis can have various effects on behavior, personality, cognition, and even psychiatric conditions. In this chapter, we will explore the role latent toxoplasmosis plays in the behavior of animals and humans, and discuss the possible mechanisms for the observed effects.
... Toxoplasma gondii is an obligatory intracellular parasite, belongs to the phylum Apicomplexa, T.gondii infects warmblooded animals (Flegr, 2013). ...
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Toxoplasmosis is a zoonotic disease caused by Toxoplasma gondii, there are two hosts , cats play an important role as definitive hosts , cattle, sheep ,goats and human may play as intermediate hosts. Humans be infected by eating tissue cysts from Not cooked flesh and eat contaminated feed or water with oocytes shed in the faecal of infected cats. diagnosis of T. gondii itself is affirmation the infection but difficult, so many laboratories use serological methods to detect immunoglobulins which specific to T. gondii : latex agglutination (LA) test, Enzyme Linked Immuno Sorbent Assay and indirect fluorescent antibody test (IFAT) those methods was differ in specificity and sensitivity there is no systematic review that can perform the state of toxoplasmosis in the definitive host. Therefore the aims of the current existing review was to decided the risk factor of T. gondii infection and demonstrated the epidemiological form of infection in cats in Iraq.
... Toxoplasma gondii, the parasitic protozoon of cats, infects about one-third of the human population in both developed and developing countries (Tenter et al., 2000). Infected humans express no specific symptoms of the life-long infection, however, they differ from non-infected subjects by a higher incidence of many diseases and disorders (Flegr & Escudero, 2016;Flegr, Klapilová, et al., 2014;Flegr, Prandota, et al., 2014) and also by specific changes in personality (Flegr, 2013;Khademvatan et al., 2013;Lindová et al., 2012) and behavior (Fekadu et al., 2010;Houdek, 2017). These behavioral differences are mostly considered to be products or by-products of the manipulative activity of Toxoplasma aimed to increase the chance of transmitting from the infected intermediate host, which can be any warm-blooded animal, to its definitive host, a cat (Webster, 2007). ...
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Humans infected by Toxoplasma gondii express no specific symptoms but manifest higher incidence of many diseases, disorders and differences in personality and behavior. The aim of this study was to compare the political beliefs and values of Toxoplasma-infected and Toxoplasma-free participants. We measured beliefs and values of 2315 responders via an online survey (477 Toxoplasma-infected) using the Political Beliefs and Values Inventory (PI34). This study showed Toxoplasma-infected and Toxoplasma-free participants of our cross-sectional study differed in three of four factors of PI34, scoring higher in Tribalism and lower in Cultural liberalism and Anti-Authoritarianism. We found sex differences in political beliefs associated with Toxoplasma infection. Infected women scored higher in tribalism and lower in cultural liberalism, compared with the Toxoplasma-free control group, while infected men scored higher in economic equity. These results fit with sexual differences in behavior and attitude observed after toxoplasmosis infection. Controlling for the effect of worse physical health and mental health had little impact, suggesting that impaired health did not cause these changes. Rather than adaptation to prevalence of parasites, as suggested by parasite-stress theory, the differences might be side-effects of long-term mild inflammatory reaction. However, to get clear picture of the mild inflammation effects, more research focused on different infectious diseases is needed.
Background. Infection with latent toxoplasmosis has been implicated in the aetiology of mental disorders. However, findings are somewhat controversial in this area. Methods. The population of this study included individuals with latent toxoplasmosis on the Internet. The sample included volunteers with latent toxoplasmosis on Facebook, Twitter, and Instagram. The sample consisted of 59 females and 58 males (117 in total) from Iran and 44 other countries. Data were collected on-line using the 71-item abbreviated version of MMPI. The collected data were analyzed employing the t-test, Mann-Whitney-U test, Kendall’s tau_b correlation test, and robust regression. Results. Findings indicated that: a) the psychological profile of patients with latent toxoplasmosis was in the normal range on the eight clinical scales on the 71-item abbreviated version of MMPI (70>T-scorse>30(, b) in the male group, the predictor variable of duration of infection had significant predictive power in predicting scores on the four clinical scales of depression, psychopathic deviation, psychasthenia , and schizophrenia in the male group, the predictor variable of age also had a significant predictive power as to scores on the scale of hypochondriasis in this group, c) in the female group, the variable of duration of infection did not predict scores on any of the eight clinical scales significantly; only was the predictor variable of age capable of predicting scores on the scales of hysteria, paranoia, psychasthenia, psychopathic-deviation, d) there was not a significant difference between male and female groups on any of the clinical scales. Conclusion: Latent toxoplasmosis did not result in any psychiatric or psychological disorders in male and female groups; however, duration of infection predicted scores on the scales of Depression, Psychopathic-Deviation, Psychasthenia, and Schizophrenia and age predicted scores on Hs in males. As to females, age predicted scores on Hysteria, Paranoia, PsychopathicDeviation, and Psychasthenia. In addition, no significant difference was found in the mean scores of the clinical scales between males and females. Practical Implications. In males with latent toxoplasmosis, it is recommended to psychologists and psychiatrists to pay attention to disorders such as hypochondriasis, depression, psychopathic deviation, psychasthenia, and schizophrenia when screening for psychiatric disorders.
Intracellular parasite Toxoplasma gondii infects up to a third of the world population. The agent is neurotrophic, with a specific affinity to glia. It is possible that latent toxoplasma infection plays a role in the pathogenesis of schizophrenia. The alteration of cognitive functions is considered as an element of vulnerability for the development of some schizophrenia subtypes in the current state of knowledge. In theory, the changes of neurotransmission, the effect of cytokines, autoimmune reactions and disorders of brain development are considered to be responsible pathogenetic mechanisms. The hypothesis of the link between Toxoplasma infection and schizophrenia is supported by these findings: 1) statistically significant increase of antibodies to Toxoplasma in antipsychotic-naive, first-episode patients, 2) the PANSS total score related to the levels of IgG antibodies to TG and the levels of IgM antibodies depending on PANSS negative symptoms in First-Episode Schizophrenia, 3) prenatal exposure to toxoplasmosis and intrauterine infections with Toxoplasma as a risk factor for schizophrenia, 4) increased levels of cognitive impairment in persons with schizophrenia who have serologic evidence of Toxoplasma infection in comparison to Toxoplasma seronegative patients, 5) cognitive and behavioural changes in infected non-schizophrenic subjects 6) specific behavioural changes in infected animals, 7) adults with schizophrenia or bipolar disorder had more exposure than controls to the definitive host of Toxoplasma in childhood - cats. Neurocognitive assessment, functional brain imaging methods and molecular genetic techniques improve our possibilities to test the involvement of Toxoplasma in the etiology of schizophrenia.
Introduction and objective: Toxoplasma gondii is an intra cellular protozoan parasite which infects 30 to 60% of the world population. A wide range of toxoplasmosis conditions has been studied, but there are still unknown damages which must be explored. In the present research, the effect of this parasite on testosterone and cortisol changes in the infected men and women was examined. Materials and methods: A total of 180 patients (73 females and 107 males), were examined for lgG anti-Toxoplasma antibody, cortisol and testosterone in their plasma. In addition, the patients also filled in personality questionnaire DASS21 (depression, anxiety, and stress). Results: Results showed that 24(%13/33) females and 39(%20) males were positive with lgG anti-Toxoplasma antibody, respectively. A statistically significant correlation between Toxoplasma infection and testosterone and cortisol increase in women and men were observed. Stress and anxiety index also increased in men and women whereas depression index increased only in men. Conclusion: The results show a direct relation between raise Toxoplasma infection and cortisol, and testosterone increase in bout men and women and high DASS21 test score in Toxoplasma infected group. Significance and impact of the study: Our results may indicate that following Toxoplasma infection, the probability of stressful condition is high.
Objective: To compare two methods of calculating total antipsychotic drug dosage with a representative patient sample in Hong Kong. Methods: Antipsychotic prescription data from 8,620 inpatients and outpatients in the New Territories West Cluster hospitals of Hong Kong were collected. The total antipsychotic dose was calculated using the chlorpromazine equivalent method and the percentage of maximum recommended method. Results: There was 97.2% concordance between these two methods, with a Spearman's rank correlation of 0.92. High doses of antipsychotic medications were prescribed for 3.2% and 2.8% of the sample based on the chlorpromazine equivalent and percentage of maximum recommended methods, respectively. Conclusions: Total antipsychotic dose expressed as a percentage of the maximum recommended dose is easy to calculate and avoids the ambiguity associated with the chlorpromazine equivalent method, besides it helps to identify patients receiving high doses of antipsychotics, thus facilitating monitoring and adherence to current guidelines.
Typically, female rats demonstrate clear mate choice. Mate preference is driven by the evolutionary need to choose males with heritable parasite resistance and to prevent the transmission of contagious diseases during mating. Thus, females detect and avoid parasitized males. Over evolutionary time scales, parasite-free males plausibly evolve to advertise their status. This arrangement between males and females is obviously detrimental to parasites, especially for sexually transmitted parasites. Yet Toxoplasma gondii, a sexually transmitted parasite, gets around this obstacle by manipulating mate choice of uninfected females. Males infected with this parasite become more attractive to uninfected females. The ability of T. gondii to not only advantageously alter the behavior and physiology of its host but also secondarily alter the behavior of uninfected females presents a striking example of the 'extended phenotype' of parasites. Toxoplasma gondii also abolishes the innate fear response of rats to cat odor; this likely increases parasite transmission through the trophic route. It is plausible that these two manipulations are not two distinct phenotypes, but are rather part of a single pattern built around testosterone-mediated interplay between mate choice, parasitism and predation.
We examine the role of the protozoan Toxoplasma gondii as a manipulatory parasite and question what role study of infections in its natural intermediate rodent hosts and other secondary hosts, including humans, may elucidate in terms of the epidemiology, evolution and clinical applications of infection. In particular, we focus on the potential association between T. gondii and schizophrenia. We introduce the novel term 'T. gondii-rat manipulation-schizophrenia model' and propose how future behavioural research on this model should be performed from a biological, clinical and ethically appropriate perspective.
The past decades have seen mounting evidence that parasites alter their host's behaviour in ways that benefit transmission, based on differences in the expression of behavioural traits between infected and control individuals, or on significant correlations between trait expression and infection levels. The multidimensional nature of host manipulation has only recently been recognised: parasites do not target single host traits, but instead suites of interrelated traits. Here, I use recent research on animal personality (behavioural differences among individuals consistent across time and situations) and behavioural syndromes (correlations at the population level among distinct behavioural traits, or between the same trait expressed in different contexts) to provide a framework from which simple testable patterns of host behavioural changes can be predicted. Following infection, a manipulative parasite could (i) change the temporal consistency of its host's behavioural responses, (ii) change the slope of a host reaction norm, i.e. the way host behavioural traits are expressed as a function of an environmental gradient, or (iii) decouple two or more host behavioural traits and/or change the way in which they correlate with each other. Two case studies involving trematode parasites and their freshwater hosts are used to provide empirical illustrations of the above scenarios. These clearly illustrate the full richness of behavioural alterations induced by parasites, and how these effects would go unnoticed using the classical trait-by-trait comparisons of mean values between parasitised and non-parasitised individuals. However, the power of animal personality and behavioural syndromes to inform research on host manipulation by parasites will only be fully realised when underlying mechanisms are elucidated and linked to their phenotypic impacts.