Our results showed that CMV infected subjects had lower scores in the personality dimension novelty seeking than the CMV-free subjects. Novelty seeking in infected subjects negatively correlated with levels of anti-CMV antibodies. Negative correlation was also found between novelty seeking and Toxoplasma-infection in Prague, while in villages and smaller cities the correlation was not significant. The effect of both infections, although highly significant, was rather low, explaining about 2 % of total variability of the novelty seeking in our experimental set. The study also revealed several other significant effects CMV or Toxoplasma infections and their interaction on personality traits. While the effect of the infections on novelty seeking was a priori expected, other effects were revealed by an ex post analysis. Therefore, the results concerning the other effects have to be corrected for multiple statistical tests. After the Bonferroni's correction for multiple tests, no ex post revealed effect remained significant.

The lower values novelty seeking in the Toxoplasma-positive subjects suggest that infected men are on average more reflective, tend to require more detailed information when making an opinion and are not easily distracted. They are also more reserved, slow, controlled; they do not waste their energy and feelings. They tend to be organized, methodical, and prefer activities with strict rules and regulations. The association between latent toxoplasmosis and low novelty seeking scores has already been reported [18]. The present study showed that the relation between toxoplasmosis and novelty seeking was not caused by parallel correlations between the risk of Toxoplasma infection and size of place of residence and between size of place of residence and novelty seeking scores. Surprisingly, toxoplasmosis and CMV infections were associated with considerably lower novelty seeking scores only in large cities. There were no significant differences in novelty seeking between infected and pathogens-free subjects in settlements with fewer than 10 thousand population (CMV) or fewer than 100 thousand population (Toxoplasma). At present we have no explanation for this phenomenon.

A previous study performed on a larger set of experimental subjects revealed that Toxoplasma-infected subjects scored lower in verbal intelligence as measured with the Otis test and showed lower probability of achieving secondary education than Toxoplasma-free subjects [18]. It was demonstrated in several countries including the Czech Republic [34] that prevalence of toxoplasmosis is higher in villages and small cities than in larger cities. At the same time, the probability of achieving higher education and possibly also higher verbal intelligence could positively correlate with the size of place of residence. Therefore, the observed effects of toxoplasmosis can in fact reflect a parallel influence of size of place of residence (and corresponding life style) on a) the risk of acquiring Toxoplasma infection and b) probability of achieving secondary education and higher verbal intelligence. This model was strongly supported by the results of the present study. All associations between Toxoplasma infection and education level or intelligence disappeared after adjustment for the effect of place of residence. It is also noteworthy that CMV infection, which shows a similar prevalence rates in villages and small and large cities, has no association with education level or intelligence.

Neither the psychopathological antecedents nor the pre-infection personality data of the subjects were available for our analysis. Based on a case-control study, it is not possible to tell whether there is a causal relation between two statistically associated factors (e.g. infection and lower novelty seeking scores) and/or to determine the direction of such a relation. Theoretically, the infection could induce personality changes, personality factors may have influenced the risk of infection and possibly a third factor, such as the socioeconomic status, may have played a role in both personality dimensions and the risk of infection. In our view, however, the most parsimonious explanation is that the infection, more precisely the presence of pathogens in the brain of infected subjects, induces changes in neurotransmitter levels, causing in turn changes in TCI personality dimensions. This hypothesis is based on several lines of indirect evidence:

a) Two different neurotropic pathogens with quite different life cycles and transmission routes are associated with the same psychological effect. This makes the existence of a third factor responsible for both lower novelty seeking scores and higher risk of infection rather unlikely. Moreover, the existence of such a factor would cause a statistical association between Toxoplasma and CMV infections. However, CMV infection was detected with equal frequency among Toxoplasma-free and Toxoplasma-infected subjects.

b) The existence of correlation between novelty seeking scores and levels of specific antibodies (significant in one-tailed tests) was observed for both Toxoplasma and CMV. Such a correlation between the intensity of personality change and specific immunity could hardly be found if novelty seeking would influence the risk of infection or if an unknown factor would independently influence both novelty seeking and the risk of infection.

c) A decrease in neophilia in naturally neophilic mice and a decrease of neophobia of naturally neophobic rats, probably caused by lower ability of discriminating between familiar and novel surroundings, was also observed in animals experimentally infected with Toxoplasma [3, 4, 8], and a related behavioral effect (the apomorphine-mediated decrease of prepulse inhibition) was observed in rats infected with CMV [48]. Therefore, the direction of the causal relation between novelty seeking-related behavioral changes and Toxoplasma/CMV infections has already been experimentally established in rodents.

d) Lower novelty seeking scores are claimed by several authors [29–33] to correlate with the background level of dopamine in the basal ganglia. The increased level of dopamine was indeed observed in mice experimentally infected both with Toxoplasma [19] and CMV [49].

The specific neurological mechanism underlying the association between the infections and novelty seeking was not the subject of the present study. The available results of neuroimmunological studies, however, suggest that several cytokines engaged in inflammation processes, like interleukins 1, 2 and 6, directly influence the level and turnover of many neuromodulators, including dopamine [50–53]. An extremely low concentration of interleukin 2 (IL-2) is able to potentiate dopamine release evoked by number of different stimuli, including K+ depolarization in mesencephalic cell cultures [54] and striatal slices [55]. Injections of IL-2 into the rat striatum have been shown to induce turning behaviors in rats that are typical of perturbation of the dopaminergic system [56] and subcutaneously administered IL-2 significantly increases locomotor activity of mice in the elevated plus-maze test [55]. Serious neuropsychiatric side effects demanding acute intervention regularly occur in oncological patients treated with IL-2 and lymphokine-activated killer cells [55, 57, 58]. Dormant forms of Toxoplasma and CMV persist in the brain of infected individuals for many years. The activation of acute disease in immunocompromised patients and immunohistochemical data obtained on mice [59] suggest that under normal conditions both diseases are kept in latent form by the host immune system. Local immune processes in the brain of subjects with latent infections are probably accompanied by local disturbances in particular cytokine levels [60–64]. This can influence the background level of neuromodulators and secondarily some of the personality dimensions.

It has been reported repeatedly that both toxoplasmosis and contact with cat, the definitive host of Toxoplasma gondii, are associated with higher risk of schizophrenia [20–28]. Similarly, schizophrenia was reported to correlate with CMV infection [65]. The background level of dopamine is supposed to play an important role in etiology of schizophrenia [66–68] and autoimmune-like effects on the dopamine system have been proposed as a possible mechanism involved in the pathogenesis of schizophrenia and Parkinson's disease [69]. Clinical investigations have detected increased levels of IL-2 in the CSF of schizophrenic patients manifesting symptoms of psychosis [70, 71]. It can be speculated that the local inflammation-induced increase in dopamine in the brain of infected subjects can be in fact the missing link between schizophrenia and Toxoplasma or CMV infection.