Search tips
Search criteria 


Logo of iranjparaThis JournalSearchAims and ScopeAuthor GuidelinesSubmit a ManuscriptThis JournalTUMS
Iran J Parasitol. 2012; 7(1): 1–17.
PMCID: PMC3488815

Latent Toxoplasmosis and Human


Toxoplasmosis is one of the most common parasitic diseases worldwide. Although estimated that one third of the world's population are infected with Toxoplasma gondii, but the most common form of the disease is latent (asymptomatic). On the other hand, recent findings indicated that latent toxoplasmosis is not only unsafe for human, but also may play various roles in the etiology of different mental disorders. This paper reviews new findings about importance of latent toxoplasmosis (except in immunocompromised patients) in alterations of behavioral parameters and also its role in the etiology of schizophrenia and depressive disorders, obsessive–compulsive disorder, Alzheimer's diseases and Parkinson's disease, epilepsy, headache and or migraine, mental retardation and intelligence quotients, suicide attempt, risk of traffic accidents, sex ratio and some possible mechanisms of T. gondii that could contribute in the etiology of these alterations.

Keywords: Toxoplasmosis, Toxoplasma gondii, Mental disorder, Behavioral parameter


Toxoplasma gondii is an intracellular protozoan that infects approximately one-third of the world's population. Members of the cat family are final hosts of T. gondii and various warm-blooded animals including humans, are intermediate host. There are three infectious stages in the life cycle of T. gondii, including: oocysts containing sporozoites, tachyzoites and bradyzoites contained in tissue cysts (1).

Infection in human generally occurs through consuming food or drink contaminated with oocysts and tissue cysts from undercooked meat. Congenital transmission and organ transplantation are also other routes of infection (1).

Different conditions such as, number of parasite, virulence of the organism, genetic background, sex, and immunological status seem to affect the course of infection (1).

Most common form of the infections in humans are latent (asymptomatic) but in some conditions including immunocompromised patients and congenitally infected fetuses and newborns, may cause severe disease (2). Symptomatic infection is usually characterized by lymphadenopathy and reticular cell hyperplasia. Congenital infections acquired during the first trimester are more severe than those acquired in the second and third trimester, in congenital disease; hepatitis and pneumonia are followed by central nervous system (CNS) involvement resulting in hydrocephalus, retinochoroiditis and cerebral calcifications (3, 4). Ocular toxoplasmosis can be seen after congenital or acquired infection as a result of acute infection or reactivation (1). In immunocompromised patients such as AIDS, toxoplasmosis almost always happens as a result of reactivation of chronic infection. In these patients, clinical symptoms consist of mental status changes, seizures, sensory abnormalities, cerebellar signs, movement disorders, and neuropsychiatric findings (1).

Toxoplasma gondii consists of three main genotypes, designated type I, II, and III which differ in virulence and epidemiological pattern. Type I strain is associated with high-level virulence in mice (5). This type has been recorded in patients with ocular toxoplasmosis (6). Type II is nonvirulent for mice but generate chronic infection with persistence of tissue cysts. This strain is also most commonly associated with human infections in Europe and North America (5). Type III is nonvirulent for mice and less frequent than type II in Europe and North America. This Type is most frequent strain from animals (5). Moreover, Type I and II strains have been recorded in patients with congenital disease and AIDS patients (7, 8).

Although, seroprevalence rate of toxoplasmosis estimated between 20%-80% in different parts of the world including Iran (9, 10), but, the most common form of the disease is latent (asymptomatic). In fact after ingestion of the parasite and proliferation of tachyzoites in various organs during the acute stage, the parasite forms cysts in the brain and establishes a chronic infection in human and rat (11, 12). A variety of brain cells, including astrocytes and neurons, can be infected (13). So, the infection may causes various hormonal and mental disorders (1417); moreover, other findings have shown that, latent toxoplasmosis can cause a wide range of behavioral changes in humans and animal models (1821).

The purpose of this review article is demonstration of new finding on the impact of latent toxoplasmosis on human.

Latent toxoplasmosis and behavioral parameters

Recent studies demonstrated that latent infection with T. gondii can alter behavioral parameters of human and rodents (18, 20). These alterations in rodents are named with the term of ‘parasite manipulation’ and in human by ‘parasite constraint’ (19). Toxoplasma gondii has only one final host (cat) but many intermediate hosts (all warm-blooded vertebrates). Rodents are persistent intermediate host reservoir for T. gondii in natural conditions; hence manipulation hypothesis mention a parasite may alter host behavior for its own benefit, usually by enhancing its transmission rate (19). Humans are dead-end hosts for T. gondii, because that rarely eaten by feline. In these conditions, induction of behavioral alterations termed as ‘parasitic constraint’ (19).

Different studies have been conducted on the relationship between latent toxoplasmosis and behavioral parameters in humans. Interestingly these parameters are different in infected men and women. For example, intelligence, affectothymia (warm, outgoing, attentive to others, kindly, easy-going, participating and likes people) and superego strength (rule-conscious, dutiful, conscientious, conforming, moralistic, staid and rule bound) are higher in infected women, while infected men have lower intelligence, superego strength and novelty seeking (low novelty seeking indicates rigid, loyal, stoic, slow-tempered and frugal personalities); both infected men and women have higher levels of guilt-proneness (they tend to be more apprehensive, self-doubting, worried, guilt prone, insecure, worrying and self-blaming) (2227).

Flegr (2007) suggested, “Infected men were more likely to disregard rules and were more expedient, suspicious, jealous, and dogmatic and infected women more likely warm hearted, outgoing, conscientious, persistent, and moralistic”(20). Furthermore, other studies showed infection with T. gondii in humans can cause diminish in reaction time and psychomotor performance (2830).

In animal models, T. gondii infected rats also observed significantly more active and less fear of novelty (neophobic fear) than uninfected animals (31, 32). Likewise, Hodcova et al. found learning capacity of T. gondii infected mice was diminished in static rod test and 8-arm radial maze test but spontaneous activity of these mice was increased in the wheel running test than non infected animals (33). Other studies showed the aversion of T. gondii infected rodents to predator odors (cat) were decreased compared to non infected animals, this event may cause increase predation risk of infected rodents and also increase transmission the parasite (3436).

These observations support consents with the “behavioral manipulation” hypothesis, which states a parasite may alter host behavior for its own benefit by enhancing its transmission rate (19).

Latent toxoplasmosis, schizophrenia and depressive disorders

Schizophrenia is a chronic, neuropsychiatric disease of uncertain cause that affects approximately 1% of people (37). Genetic and environmental factors including some infections (e.g. rubella, influenza, T. gondii, herpes simplex virus type 2 (HSV-2)) play roles in its etiology (38). In recent years, many studies have reported the higher incidence of Toxoplasma infection in schizophrenia patients. Majority of case control studies have been conducted on anti T. gondii antibodies test in schizophrenia patients; confirmed the higher infection with T. gondii (3956). For example, 42.1% of patient with first-episode schizophrenia and 11.1% of healthy controls were seropositive to T. gondii infection (P < 0.007) (39).

The result of a meta-analysis of 42 studies which carried out in 17 countries showed the odds ratio of T. gondii antibodies in individuals with schizophrenia was OR 2.73 (57).

Another study demonstrated individuals with higher levels of T. gondii IgG antibodies significantly having more severe symptoms of psychoses (55). In addition, significant positive associations between increased levels of T. gondii IgG antibodies in schizophrenia patients were also observed with hazard ratio of 1.24 (58).

In addition infection with T. gondii may confer an increased risk of mortality in individuals with schizophrenia. Dickerson et al. have examined antibodies to T. gondii in 358 patients with schizophrenia and followed-up these peoples up to 5 years. The results indicated that the overall mortality rate was 8.6% for schizophrenia patients who were seropositive to Toxoplasma compared with 1.7% for seronegative schizophrenia patient (P < 0.003) (59).

There are also evidences that maternal and prenatal infection with T. gondii are as risk factors for schizophrenia and psychoses in adult offspring (60, 61). In this regard, Brown et al., have measured maternal anti-T. gondii IgG antibody in 63 women who their infants later developed schizophrenia or other schizophrenia spectrum disorders. Accordingly, the OR of schizophrenia and schizophrenia spectrum disorders increased in patients with high maternal anti-T. gondii IgG antibody (OR = 2.61; P = 0.051) (61). Another study in Denmark showed risk of schizophrenia in neonates with high levels of maternal anti-T. gondii IgG antibodies was significantly higher than control subjects (OR = 1.79; P = 0.045).

Recently, Horacek et al. found the gray matter density in the brain of schizophrenia patients who latently infected with T. gondii was significantly reduced than Toxoplasma negative schizophrenia patients in the caudate, median cingulate, thalamus and occipital cortex and in the left cerebellar hemispheres (62).

Furthermore, there are evidences that different genotypes of T. gondii have diverse effects on the course of psychosis. In this regard, Xiao et al. had investigated different genotypes of T. gondii in 219 pregnant women whose children developed schizophrenia and psychotic illnesses in adult life (63) and found that the risk for the development of psychoses in the offspring of mothers infected with genotype I T. gondii were significantly higher compared with the matched unaffected control mothers (P = 0.03).

The association of higher titers of T. gondii IgG antibody with anxiety, depression and schizophrenia spectrum disorders was also observed. Groër et al. observed higher titers of T. gondii IgG antibody was positively correlated with depression and anxiety in women during pregnancy. Indeed, depression and anxiety in pregnant women infected with genotype I T. gondii were highest than other genotypes; but this was not significant (64). Mothers with high titers of T. gondii IgG antibodies had significantly higher risk of schizophrenia spectrum disorders (65).

Some antischizophrenic and antipsychotic drugs can inhibit proliferation of T. gondii in vitro (6668); interestingly, Kar and Misra reported a depressed patient with Toxoplasma seropositivity that showed poor response to anti-depressants drugs. The patient successfully treated with anti-depressants drugs only after treatment by anti-Toxoplasma drugs (pyrimethamine and sulphadiazine) (69).

Latent toxoplasmosis and obsessive–compulsive disorder

Obsessive-Compulsive Disorder (OCD) is an anxiety disorder characterized by recurrent, unwanted thoughts (obsessions) and/or repetitive behaviors (compulsions). Repetitive behaviors such as hand washing, counting, checking, or cleaning are often performed with the hope of preventing obsessive thoughts or making them go away. OCD affects about 2.2 million American adults (70).

The rate of anti-T. gondii IgG antibodies among 42 patients with OCD and 100 healthy volunteers was studied and the seropositive rate among OCD patients was 47.62% significantly higher than the rate in healthy volunteers (19%; P<0.01) (71). Brynska et al. reported two children with symptoms of obsessive-compulsive disorder along with acquired toxoplasmosis. They found that OCD symptoms were observed immediately following acquired toxoplasmosis. These children were treated with anti-Toxoplasma drugs without any psy-chopharmacological treatment that caused significant improvement of OCD symptoms (72).

Latent toxoplasmosis and suicide attempt

Suicide is the act of deliberately killing oneself. Risk factors for suicide include mental disorder (such as depression, personality disorder, alcohol dependence, or schizophrenia), and some physical illnesses, such as neurological disorders, cancer, and HIV infection. Global burden of suicide is one million deaths per year (73). In three independent studies, seroprevalence of toxoplasmosis in people who had suicide attempt were investigated (7476). Arling et al. compared seropositivity and antibody titers of T. gondii between 99 patients with recurrent mood disorders with history of suicide attempt versus 119 patients with recurrent mood disorders without history of suicide attempt and 39 healthy controls individuals in US (74). Accordingly, no significant relation between T. gondii seropositivity and suicide attempt status was found; but the titers of T. gondii IgG antibodies in suicide attempters had significantly higher than non suicide attempters (P = 0.004). In addition, predictive association between history of suicide attempt and titers of T. gondii IgG antibodies was OR = 1.55, (P=0.006). Yagmur et al. have measured anti-T. gondii antibodies (IgG, IgM) in 200 cases of suicide attempts and 200 healthy volunteers in Turkey (75). As the result the positive rate for anti-T. gondii IgG antibodies was 41% and for IgM was 5.5% in suicide attempters, while the positive rate in controls were 28% and 5% for IgG and IgM antibodies. This differences for anti-T.gondii IgG antibody was statistically significant (P=0.004). In addition, there is a positive association between rates T. gondii infection and suicide in women of postmenopausal age (76).

Latent toxoplasmosis and risk of traffic accidents

Traffic accidents are among the main reasons for public health damage. Nearly 1.3 million people die each year on the world's roads, and between 20 and 50 million sustain non-fatal injuries (77). In four studies, seroprevalence rate of toxoplasmosis in victims of traffic accidents and control group were investigated (7881).

Flegr et al. in Prague (Czech Republic) found the risk of an accident in individuals with latent toxoplasmosis was 2.65 times higher than the toxoplasmosis-negative individuals (78). Moreover, the value of the odds ratio (OR) significantly increased with level of anti-Toxoplasma antibody titer (P < 0.0001); the OR of risk of an accident in subjects with low, moderate and high antibody titers were 1.86, 4.78 and 16.03 respectively.

The seroprevalence rate of T. gondii infection in victims of traffic accidents and in control group were 32.43% and 8.64% respectively (P <0.0001) in Turkey (79). In another study, the seroprevalence rate of toxoplasmosis was 53.5% for victims of traffic accidents and 28.0% in control groups (P <0.0001) (80). Furthermore, RhD molecule with unknown mechanisms has protective effect against traffic accidents in Toxoplasma positive individuals. In this study, 3890 male draftees were tested for Toxoplasma infection and RhD phenotype. The incidence rate of traffic accidents during their military service would be monitored. The result showed the probability of a traffic accident in RhD-negative individuals with high titers of anti-Toxoplasma antibodies was more than six times higher rate than Toxoplasma negative or RhD positive individuals (81).

Latent toxoplasmosis, Alzheimer's diseases and Parkinson's disease

Alzheimer's disease is the most common neurodegenerative disorders that results in the irreversible loss of neurons, particularly in the cortex and hippocampus. Approximate prevalence of the disease is 1% among those 65 to 69 years of age, rising to 40 to 50 percent among persons 95 years of age and over. It is characterized clinically by progressive impairment in memory, judgment, decision making, orientation to physical surroundings, and language (82). Parkinson's disease is also the second most common neurodegenerative disorder, after Alzheimer's disease. Approximate prevalence of Parkinson's disease is 0.5 to 1 percent among persons 65 to 69 years of age, and increases with age to 1% to 3% among persons 80 years of age and older. The clinical manifestations of Parkinson's disease are characterized by resting tremor, bradykinesia, rigidity, and postural instability (82).

In a case control study about latent toxoplasmosis and Alzheimer's disease, the seropositive rate of anti-T. gondii IgG antibodies among individuals with Alzheimer's disease was 44.1% significantly higher those than control groups 24.3% (83). In addition, two studies evaluated the seroprevalence rate of toxoplasmosis in patients with Parkinson's disease.

The seroprevalence rate of anti-T gondii IgG antibodies in the patients with Parkinson's disease and control groups were 42.3 and 22.5% respectively, which is statistically significant (P = 0.006) (84). Although anti-T. gondii antibodies were detected in 50% and 40% of the patients with Parkinson's disease and in the control groups respectively, but the difference was not statistically significant (85).

Latent toxoplasmosis, epilepsy, headache and or migraine

Epilepsy is the most common serious brain disorder worldwide affecting people of all ages, race and social class. It is characterized by recurrent seizures to severe and prolonged convulsions. The annual incidence rate of epilepsy is around 40–70 per 100,000 in industrialized countries and 100–190 per 100,000 in resource-poor countries (86). Several etiologic factors including infections (viral, bacterial, fungal and parasitic infection) in the etiology of epilepsy are involving (87).

In order to determine whether there is a relation between toxoplasmosis and epilepsy, Stommel et al. had measured anti-T.gondii IgG antibodies in 22 patients with cryptogenic epilepsy and 23 healthy controls. They found thta anti-T.gondii IgG antibodies among epileptic patients were significantly elevated compared to controls (59% increased in optical density, P=0.013) (88).

Also, in a case-control study 52% of cryptogenic epilepsy patients, 22% of known cause epilepsy patients and 18% of healthy controls were seropositive to T. gondii, the seropositive rate in cryptogenic epilepsy patients was statistically significant from other groups (P <0.01) (89). In contrast, there were not any associations between epilepsy and seropositive rates of T. gondii and Toxocara canis in 100 cryptogenic epileptic patients and 50 healthy volunteers (90).

The prevalence of anti-T.gondii IgG antibody in the migraine patient was statistically higher than control groups (91). The seropositive rate for patients with migraine was 44.2%, in healthy controls was 26.0%, and for control subjects with headache due to rhinosinusitis was 24%.

Palmer (2007) had performed a meta-analysis to clarify the association between latent toxoplasmosis and cryptogenic epilepsy. This study compared the seroprevalence of toxoplasmosis rates in 17 different countries, against the prevalence rates for epilepsy in those regions; and three case controlled studies about latent toxoplasmosis and cryptogenic epilepsy. The result showed that odds ratio of the three case controlled studies is 4.8, which indicated that epilepsy is 4.8 times more prevalent among Toxoplasma seropositive persons (92). Furthermore, the ecological study showed a strong association between the prevalence of epilepsy and the seroprevalence of toxoplasmosis within the same region (P<0.001). Palmer concludes, “The prevalence of toxoplasmosis is an important factor in the prevalence of epilepsy”. “An area with a reduced burden of toxoplasmosis will also have a reduced burden of epilepsy” and the higher seroprevalence of toxoplasmosis is associated with higher the rate of epilepsy in the population (92).

Latent toxoplasmosis, mental retardation and intelligence quotients (IQ)

Mental retardation (MR) is one of the most common neuropsychiatric disorders among children and adolescents. Mental retardation is more frequent in males and its prevalence among young individuals is about 1%. Various factors including congenital infections are involved on its etiology (93). Prenatal infection with Toxoplasma and rubella probably responsible for about 2-3% of all the cases of mental deficiency, cytomegalovirus infection is also associated with about 10% of microcephalic mental deficiency (94).

A systematic investigation on the subject of latent toxoplasmosis and cognitive functions in Toxoplasma infected and non infected children (with comparison of social background, physical, behavior and intelligence quotients) showed an average IQ of infected children had lower than the controls (93 versus 110 respectively) (95). In addition, the results of a cases-control study among 450 mental retarded and 395 healthy children in Brazil displayed that 54.8% of the cases and 29.3% of controls were seropositive to Toxoplasma. Retinochoroiditis in mental retarded children was fourfold more prevalent than the healthy children and maternal exposure to cats and contact with soil were associated with an increase risk of mental retardation in this study (96). In this regard, Flegr et al. searched personality parameters of 857 Toxoplasma positive and negative military conscripts. They observed various personality parameters in the infected individuals were significantly lower than non infected controls. Moreover, they unexpectedly observed intelligence quotients (IQ) and educational levels of infected individuals were significantly lower than non infected individuals (25).

Latent toxoplasmosis and sex ratio

The secondary sex ratio (the ratio of boy to girl at birth) is around 0.51 in most populations. This ratio may be influenced by various factors such as stress, immunosuppression, and age, the sex of preceding siblings, paternal endocrine disruption, and socioeconomic status of parents (97). A remarkable study in this regard showed that latent toxoplasmosis affect on the sex ratios in human. The results of a retrospective cohort study among 1,803 infants born from 1996 to 2004 in Czech Republic (with regarding the mother's age, concentration of anti-Toxoplasma antibodies, previous deliveries and abortion and the sex of the newborn) showed the secondary sex ratio in 454 Toxoplasma positive mothers was increased (proportion of males, 0.608) than in 1,349 Toxoplasma negative mothers (proportion of males, 0.527; P=0.0027), also after according of antibody concentration, the probability of the birth of a boy was increased with the increasing of titer of anti-Toxoplasma antibodies up to a value of 0.72 for 111 mothers with the highest titers; on the other word, “for every 260 boys born, 100 girls are born to women with the highest concentration of anti-Toxoplasma antibodies. Another study on mouse models reveal that mice with congenital toxoplasmosis in the early phase of latent infection produced a higher sex ratio and in the later phase of infection had a lower sex ratio than controls (98). Following the previous studies, Kaňková et al. suggested the immunosuppression effects of latent toxoplasmosis may increase sex ratio in mice and human. During latent toxoplasmosis in mice, significant modulation of the immune response and cytokine production occurred which it affect the secondary sex ratio (99).

Some possible mechanisms of T. gondii that could contribute in the etiology of neurological and behavioral abnormalities

Brain is one of the most important locations for T. gondii cysts formation. A variety of brain cells, including astrocytes and neurons, can be infected (13). Various alterations such as anatomical, immunological, pathological, neurotransmitter and genes expression may occur during infection of brain with T. gondii (4, 100102). Some of these alterations may also play roles in etiology of various neurological disorders.

Different neurological diseases of humans including schizophrenia, depression, Alzheimer's diseases and Parkinson diseases are associated with hippocampus and amygdala abnormalities (103109). The hippocampus is a bilateral incurved seahorse-shaped structure of the cerebral cortex. It is involved in physiopathological processes of higher functions, like learning, memory, consciousness and information processing, language (110). The amygdala is also an almond-shaped group of nuclei at the heart of the telencephalon. It is associated with a range of cognitive functions, including emotion, learning, memory, attention and perception (111). There are evidences that Toxoplasma infection have greatest impacts on the hippocampus and amygdala. Vyas et al. studied bioluminescence imaging of the brain of rats infected with T. gondii (35). They found the density of tissue cyst was higher in amygdala region. Hermes et al. also investigated the effects of T. gondii infection on various neurological and behavioral abnormalities in chronically infected mice (101) and observed various factors such as inflammations and pathological findings were more common in hippocampus areas. The weight of brain in chronically infected mice was also decreased; moreover, in a magnetic resonance imaging (MRI) study a mild to moderate ventricular dilatation of the brain of chronically infected mice was revealed (101).

Another likely hypothesis which T. gondii could cause neurodegenerative and psychiatric disorders, is modulation of different neurotransmitters especially dopamine in brain by the parasite (112114). The T. gondii genome is known to contain 2 aromatic amino acid hydroxylases that potentially could directly affect dopamine and/or serotonin biosynthesis. Dopamine is an important neurotransmitter which plays various roles in etiology of neuropsychological disorders including schizophrenia and other neurological diseases such as depression, Alzheimer's disease and Parkinson disease (112). Dopamine levels are also often increased in schizophrenia patients (112) and decreased in patients with Alzheimer's disease, Parkinson's disease and major depression (113). In this regards, serotonin or 5-hydroxy-3-indole acetic acid, norepinephrine, homovanillic acid and dopamine in the brain of acute and chronic Toxoplasma infected mice were measured so dopamine level was 14% increased in chronic infection but it was normal in acute infection. Homovanillic acid was 40% raised in acute but not in chronic infection. Norepinephrine was 28% decreased in acute but not in chronic infection. Although serotonin is implicated in a broad range of serotonin disorders like depression, schizophrenia, and Parkinson's disease, but it was not changed in acute and chronic infected mice (102). Treatment with a dopamine reuptake inhibitor (GBR 12909) alters the behavior of the mice infected with T. gondii (115). Treatment of infected rats with the haloperidol (a typical antipsychotic known dopamine D2 antagonist) and valproic acid (a mood-stabilizing drug use for treatment of epilepsy and bipolar disorder, but the mechanisms of its actions not fully understood) can reversed loss of fear to predator odor (116). Furthermore, T. gondii has two genes encoding tyrosine hydroxylase which that produces L-DOPA (117). This finding helps to better understand about dopamine alterations within the brain infected with T. gondii.

There are also evidences that inflammatory responses to infections may contribute to developing schizophrenia and related psychotic disorders (118, 119). Likewise, inflammatory responses are the innate defense against Toxoplasma infection (120).

Increased maternal levels of the inflammatory cytokine IL-8 and TNFα during pregnancy are associated with an increased risk for schizophrenia and psychotic illness among offspring (121, 122). Elevated IL-8 levels in pregnant women with anti-T gondii IgM antibody were also reported (123). IL-8 is responsible for activation and recirculation of neutrophils and increase during early infection with T. gondii (124).

Several reports described increased levels of IL-6, IL-2, and IL8 in schizophrenia patients (125129). IL-6 is also associated with clinical feature of schizophrenia (127). Decrease levels of IL-2 and IFNγ were reported in schizophrenia patients during treatment with anti psychotic drugs (130, 131). IL-6 have protective role during early infection with T. gondii and IL-6 deficient mice are more susceptible for T. gondii infection (132). IL-6 is also a marker of ocular toxoplasmosis (133). There is evidence that Toxoplasma infected astrocytes and microglial cells release of IL-1α, IL-6 and granulocyte/macrophage colony-stimulating factor (GM-CSF) (134). On the other hand, IL-6 may mediate the exacerbation of autoimmune disorders in the CNS; in addition, there is strong association between IL-6 and neurotransmitter production (135). Furthermore, in vitro stimulation of neurons to secrete dopamine and probably other catecholamines by IL-6 were also reported (136).

Another possible correlation between T. gondii infection and schizophrenia is tryptophan metabolism. More than 95% of L-tryptophan in mammals is degraded through the kynurenine pathway. The two enzymes are capable of catalyzing the first step in the pathway, tryptophan 2, 3-dioxygenase (TDO) and indoleamine dioxygenase (IDO), which regulate of kynurenine metabolism (137, 138). The activity of IDO is mainly stimulated by IFN-γ and IL-2 (137). Kynurenic acid (KYNA) is an endogenous antagonist of both N-methyl-D-aspartate (NMDA) and α7 nicotinic acetylcholine (α7nACh) receptors. These two receptors are widely are involved in physiological processes underlying learning, memory and cognitive processes. The activities of both TDO and IDO in the brain are normally very low; but in some pathophysiological conditions like inflammation, activities of these receptors may increase that result high levels of KYNA. High levels of KYNA may contribute to the patients’ cognitive impairment (138139). KYNA elevates in CSF of schizophrenia Patients (140142).

On the other hand, tryptophan is an essential amino acid for T. gondii replication (143); and degradation of intracellular tryptophan by IDO which it mediated by IFN-γ inhibit intracellular replication of T. gondii (143, 144).

Astrocytes play a pivotal role in the production of KYNA in the CNS, because astrocytes are the main source of KYNA (119). Likewise, astrocytes are one of the most important cells that invade by T. gondii (145); astrocytes degraded tryptophan by IDO to inhibit T. gondii replication (145). Although, there are no any direct evidences which whether T. gondii infected cells produce KYNA after degradation of tryptophan by IDO but it is plausible.


In this review article, new aspects of the latent toxoplasmosis discussed. About one third of the world's populations are latently infected with T. gondii without any clinical symptoms; however, recent studies indicated that latent toxoplasmosis may be playing various roles in the etiology of different mental disorders. The pathphysiology of mental illnesses originated from the brain dysfunction. Because the brain is one of the most important sites for T. gondii cysts formation, hence various alterations in brain may occur during infection. Some of these alterations may also play roles in etiology of various mental disorders. Until now, different hypotheses proposed that Toxoplasma infection involve in pathphysiology of mental illnesses. The role of T. gondii infection in hippocampus and amygdala abnormalities, neurotransmitters alterations (particularly dopamine), inflammatory responses in brain, tryptophan metabolism and kynurenic acid formation are the most of these hypotheses.


We thank Mr. Ali Abdoli for his assistance in preparation of the manuscript. The authors declare that there is no conflict of interests.


1. Montoya JM, Liesenfeld O. Toxoplasmosis. Lancet. 2004;363:1965–1976. [PubMed]
2. Weiss LW, Dubey JP. Toxoplasmosis: A history of clinical observations. Int J Parasitol. 2009;39:895–901. [PMC free article] [PubMed]
3. Hill D, Dubey JP. Toxoplasma gondii: transmission, diagnosis and prevention. Clin Microbiol Infect. 2002;8:634–640. [PubMed]
4. Bhopale GM. Pathogenesis of toxoplasmosis. Comp Immun Microbiol Infect Dis. 2003;26:213–222. [PubMed]
5. Maubon D, Ajzenberg D, Brenier-Pinchart MP, Darde ML, Pelloux H. What are the respective host and parasite contributions to toxoplasmosis? Trends Parasitol. 2008;24:299–303. [PubMed]
6. Vallochi AL, Muccioli C, Cristina Martins M, Silveira C, Belfort R, Vicente Rizzo L. The Genotype of Toxoplasma gondii Strains Causing Ocular Toxoplasmosis in Humans in Brazil. Am J Ophthalmol. 2005;139:350–351. [PubMed]
7. Ajzenberg D, Cogne N, Paris L, Bessieres MH, Thulliez P, Fillisetti D, Pelloux H, Marty P, Dardé ML. Genotype of 86 Toxoplasma gondii isolates associated with human congenital toxoplasmosis and correlation with clinical findings. J Infect Dis. 2002;186:684–689. [PubMed]
8. Khan A, Su C, German M, Storch GA, Clifford DB, Sibley LD. Genotyping of Toxoplasma gondii strains from immunocompromised patients reveals high prevalence of type I strains. J Clin Microbiol. 2005;43(12):5881–7. [PMC free article] [PubMed]
9. Tenter AM, Heckeroth AR, Weiss LM. Toxoplasma gondii: from animals to humans. Int J Parasitol. 2000;30:1217–1258. [PMC free article] [PubMed]
10. Shahmoradi A, Rezaian M, Dalimi A. Sheep an important reservoir of human toxoplasmosis in Iran. Med J IR.Iran. 1993;7(3):173–174.
11. Sharifian M, Dalimi A, Kazemi B. Early diagnosis of toxoplasmosis by PCR method in the blood of experimentally infected rats. J Vet Res. 2003;58(4):323–327.
12. Zare F, Dalimi A, Ghaffarifar F. Detection of active Toxoplasma godii (RH strain) in the different body tissues of experimentally infected rats. Modares J Med Sci. 2006;9(1):19–23.
13. Carruthers VB, Suzuki Y. Effects of Toxoplasma gondii infection on the brain. Schizophr Bull. 2007;33:745–751. [PMC free article] [PubMed]
14. Stahl W, Kaneda Y, Noguchi T. Reproductive failure in mice chronically infected with Toxoplasma gondii . Parasitol Res. 1994;80:22–28. [PubMed]
15. Stahl W, Kaneda Y. Impaired thyroid function in murine toxoplasmosis. Parasitology. 1998;117:217–22. [PubMed]
16. Abdoli A, Dalimi A, Movahedin M. Impaired reproductive function of male rats infected with Toxoplasma gondii . Anderolgia. 2012 doi: 10.1111/j.1439-0272.2011.01249.x. [Epub ahead of print] [PubMed] [Cross Ref]
17. Yolken RH, Dickerson FB, Fuller Torrey E. Toxoplasma and schizophrenia. Parasite Immunol. 2009;31:706–15. [PubMed]
18. Flegr J. Effects of Toxoplasma on Human Behavior. Schizophr Bull. 2007;33:757–760. [PMC free article] [PubMed]
19. Webster JP. Rats, cats, people and parasites: the impact of latent toxoplasmosis on behavior. Microb Infect. 2001;3:1037–1045. [PubMed]
20. Webster JP. The Effect of Toxoplasma gondii on animal behavior: Playing Cat and Mouse. Schizophr Bull. 2007;33:752–756. [PMC free article] [PubMed]
21. Abdoli A, Bahrami F, Dalimi A, Ghaffarifar F. Effect of toxoplasmosis on central nervous system. J Contemporary Neuroscience. 2011;31-31:5–15.
22. Flegr J, Hrdy I. Influence of chronic toxoplasmosis on some human personality factors. Folia Parasitol. 1994;41:122–126. [PubMed]
23. Flegr J, Zitkova S, Kodym P, Frynta D. Induction of changes in human behavioure by protozoan Toxoplasma gondii . Parasitology. 1996;113:49–54. [PubMed]
24. Flegr J, Kodym P, Tolarová V. Correlation of duration of latent Toxoplasma gondii infection with personality changes in women. Biol Psychol. 2000;53:57–68. [PubMed]
25. Flegr J, Preiss M, Klose J, HavlIcek J, Vitakova M, Kodym P. Decreased level of psychobiological factor novelty seeking and lower intelligence in men latently infected with the protozoan parasite Toxoplasma gondii Dopamine, a missing link between schizophrenia and toxoplasmosis? Biol Psychol. 2003;63:253–268. [PubMed]
26. Novotna M, Havlicek J, Smith P, Kolbekova P, Skallova A, Klose J, Gasva Z, Pisacka M, Sechovska M, Flegr J. Toxoplasma and reaction time: role of toxoplasmosis in the origin, preservation and geographical distribution of Rh blood group polymorphism. Parasitology. 2008;135:1253–1261. [PubMed]
27. Lindova J, Novotna M, Havlıcek J, Jozıfkova E, Skallova A, Kolbekova P, Hodny Z, Kodym P, Flegr J. Gender differences in behavioural changes induced by latent toxoplasmosis. Int J Parasitol. 2006;36:1485–1492. [PubMed]
28. Havlicek J, Gasova Z, Smith AP, Zvara K, Flegr J. Decrease of psychomotor performance in subjects with latent ‘asymptomatic’ toxoplasmosis. Parasitology. 2001;122:515–520. [PubMed]
29. Novotná M, Hanusova J, Klose J, Preiss M, Havlicek J, Roubalová K, Flegr J. Probable neuroimmunological link between Toxoplasma and cytomegalovirus infections and personality changes in the human host. BMC Infect Dis. 2005;5:54. [PMC free article] [PubMed]
30. Flegr J, Novotná M, Lindová J, Havlíček H. Neurophysiological effect of the Rh factor. Protective role of the RhD molecule against Toxoplasma-induced impairment of reaction times in women. Neuroendocrinol Lett. 2008;29:475–481. [PubMed]
31. Webster JP. The effect of Toxoplasma gondii and other parasites on activity levels in wild and hybrid Rattus norvegicus. Parasitology. 1994;109:583–589. [PubMed]
32. Berdoy M, Webster JP, Macdonald DW. Parasite-altered behaviour: is the effect of Toxoplasma gondii on Rattus norvegicus specific? Parasitology. 1995;111:403–409. [PubMed]
33. Hodcova H, Kodym P, Flegr J. Poorer results of mice with latent toxoplasmosis in learning tests: impaired learning processes or the novelty discrimination mechanism? Parasitology. 2007;134:1329–1337. [PubMed]
34. Berdoy M, Webster JP, Macdonald DW. Fatal attraction in rats infected with Toxoplasma gondii . Proc R Soc Lond B. 2000;267:1591–1594. [PMC free article] [PubMed]
35. Vyas A, Seon-Kyeong K, Giacomini N, Boothroyd JC, Sapolsky RM. Behavioural changes induced by Toxoplasma infection of rodents are highly specific to aversion of cat odours. Proc Nat Acad Sci USA. 2007;104:6442–6447. [PubMed]
36. Lamberton PHL, Donnelly CA, Webster JP. Specificity of the Toxoplasma gondii-altered behaviour to definitive versus non-definitive host predation risk. Parasitology. 2008;135:1143–1150. [PubMed]
37. Freedman R. Schizophrenia. N Engl J Med. 2003;349:1738–1749. [PubMed]
38. Brown AS. The environment and susceptibility to schizophrenia. Prog Neurobiol. 2011;93:23–58. [PMC free article] [PubMed]
39. Yolken RH, Bachmann S, Rouslanova I, Lillehoj E, Ford G, Torrey EF, Schroeder J. Antibodies to Toxoplasma gondii in individuals with first-episode schizophrenia. Clin Infect Dis. 2001;32:842–844. [PubMed]
40. Cetinkaya Z, Yazar S, Gecici O, Namli MN. Anti-Toxoplasma gondii antibodies in patients with schizophrenia—preliminary findings in a Turkish sample. Schizophr Bull. 2007;33:789–91. [PMC free article] [PubMed]
41. Dogruman-Al F, Aslan S, Yalcin S, Kustimur S, Turk S. A possible relationship between Toxoplasma gondii and schizophrenia: A seroprevalence study. Int J Psychiatry Clin Pract. 2009;13:82–87. [PubMed]
42. Leweke FM, Gerth CW, Koethe D, Klosterkotter J, Ruslanova I, Krivogorsky B, Torrey EF, Yolken RH. Antibodies to infectious agents in individuals with recent onset schizophrenia. Eur Arch Psychiatry Clin Neurosci. 2004;25:4–8. [PubMed]
43. Alipour A, Shojaee S, Mohebali M, Tehranidoost M, Abdi Masoleh F, Keshavarz H. Toxoplasma infection in schizophrenia patients: A comparative study with control group. Iranian J Parasitol. 2011;6:31–37. [PMC free article] [PubMed]
44. Daryani A, Sharif M, Hosseini SH, Karimi SA, Gholami S. Serological survey of Toxoplasma gondii in schizophrenia patients referred to Psychiatric Hospital, Sari City, Iran. Trop Biomed. 2010;27:476–482. [PubMed]
45. Hamidinejat H, Ghorbanpoor M, Hosseini H, Alavi SM, Nabavi L, Razi Jalali MH, Pourmehdi Borojeni M, Jafari H, Mohammadaligol S. Toxoplasma gondii infection in first-episode and inpatient individuals with schizophrenia. Int J Infect Dis. 2010;14:e978–e981. [PubMed]
46. Yuksel P, Alpay N, Babur C, Bayar R, Saribas S, Karakose AR, Aksoy C, Aslan M, Mehmetali S, Kilic S, Balcioglu I, Hamanca O, Dirican A, Kucukbasmaci A, Oner A, Torun MM, Kocazeybek B. The role of latent toxoplasmosis in the aetiopathogenesis of schizophrenia – the risk factor or an indication of a contact with cat? Folia Parasitol. 2010;57:121–128. [PubMed]
47. Krause D, Matz J, Weidinger E, Wagner J, Wildenauer A, Obermeier M, Riedel M, Müller N. The association of infectious agents and schizophrenia. World J Biol Psychiatry. 2010;11:739–743. [PubMed]
48. Wang HL, Wang GH, Li QY, Shu S, Jiang MS, Guo Y. Prevalence of Toxoplasma infection in first-episode schizophrenia and comparison between Toxoplasma-seropositive and Toxoplasma-seronegative schizophrenia. Acta Psychiatrica Scand. 2006;114:40–48. [PubMed]
49. Wang H, Yolken RH, Hoekstra PJ, Burger H, Klein HC. Antibodies to infectious agents and the positive symptom dimension of subclinical psychosis: The TRAILS study. Schizophr Res. 2011;129:47–51. [PubMed]
50. Alvarado-Esquivel C, Alanis-Quiñones OP, Arreola-Valenzuela MA, Rodríguez-Briones A, Piedra- Nevarez LJ, Duran-Morales E, Estrada-Martínez S, Martínez-García SA, Liesenfeld O. Seroepidemiology of Toxoplasma gondii infection in psychiatric inpatients in a northern Mexican city. BMC Infect Dis. 2006;6:178. [PMC free article] [PubMed]
51. Alvarado-Esquivel C, Urbina-Álvarez JD, Estrada-Martínez S, Torres-Castorena A, Molotla-de-León G, Liesenfeld O, Dubey JP. Toxoplasma gondii infection and schizophrenia: A case control study in a low Toxoplasma seroprevalence Mexican population. Parasitol Int. 2011;60:151–155. [PubMed]
52. El-Sahn AA, Shatat HZ, Ghitany EM. Seropositivity of toxoplasmosis in patients with schizophrenia. J Egypt Public Health Assoc. 2005;80:509–24. [PubMed]
53. Tanyuksel M, Uzun O, Araz E, Koru O, Babur C. Possible role of toxoplasmosis in patients with first-episode schizophrenia. Turk J Med Sci. 2010;40:399–404.
54. Bachmann S, Schröder J, Bottmer C, Torrey EF, Yolken RH. Psychopathology in first-episode schizophrenia and antibodies to Toxoplasma gondii . Psychopathology. 2005;38:87–90. [PubMed]
55. Amminger GP, McGorry PD, Berger GE, Wade D, Yung AR, Phillips LJ, Harrigan SM, Francey SM, Yolken RH. Antibodies to infectious agents in individuals at ultra-high risk for psychosis. Biol Psychiatry. 2007;61:1215–7. [PubMed]
56. Hinze-Selch D, Däubener W, Eggert L, Erdag S, Stoltenberg R, Wilms S. A controlled prospective study of Toxoplasma gondii infection in individuals with schizophrenia: beyond seroprevalence. Schizophr Bull. 2007;33:782–8. [PMC free article] [PubMed]
57. Torrey EF, Bartko JJ, Lun Z-R, Yolken RH. Antibodies to Toxoplasma gondii in patients with schizophrenia: a meta-analysis. Schizophr Bull. 2007;33:729–736. [PMC free article] [PubMed]
58. Niebuhr DW, Millikan AM, Cowan DN, Yolken R, Li Y, Weber NS. Selected infectious agents and risk of schizophrenia among U.S. military personnel. Am J Psychiatry. 2008;165:99–106. [PubMed]
59. Dickerson F, Boronow J, Stallings C, Origoni A, Yolken R. Toxoplasma gondii in individuals with schizophrenia: Association with clinical and demographic factors and with mortality. Schizophr Bull. 2007;33:737–740. [PMC free article] [PubMed]
60. Mortensen PB, Nørgaard-Pedersen B, Waltoft BL, Sørensen TL, Hougaard D, Torrey EF, Yolken R. Toxoplasma gondii as a risk factor for early-onset schizophrenia: Analysis of filter paper blood samples obtained at birth. Biol Psychiatry. 2007;61:688–693. [PubMed]
61. Brown AS, Schaefer CA, Quesenberry CP, Liu L, Babulas VP, Susser ES. Maternal exposure to toxoplasmosis and risk of schizophrenia in adult offspring. Am J Psychiatry. 2005;162:767–773. [PubMed]
62. Horacek J, Flegr J, Tintera J, Verebova K, Spaniel F, Novak T, Brunovsky M, Bubenikova-Valesova V, Holub D, Palenicek T, Höschl C. Latent toxoplasmosis reduces gray matter density in schizophrenia but not in controls: Voxel-based-morphometry (VBM) study. World J Bioll Psychiatry. 2011 doi: 10.3109/15622975.2011.573809. [Epub ahead of print] [PubMed] [Cross Ref]
63. Xiao J, Buka SL, Cannon TD, Suzuki Y, Viscidi RP, Torrey EF, Yolken RH. Serological pattern consistent with infection with type I Toxoplasma gondii in mothers and risk of psychosis among adult offspring. Microb Infect. 2009;11:1011–1018. [PubMed]
64. Groër MW, Yolken RH, Xiao JC, Beckstead JW, Fuchs D, Mohapatra SS, Seyfang A, Postolache TT. Prenatal depression and anxiety in Toxoplasma gondii-positive women. Am J Obstet Gynecol. 2011;204(5):433.e1–7. [PMC free article] [PubMed]
65. Pedersen MG, Stevens H, Pedersen CB, Nørgaard-Pedersen B, Mortensen PB. Toxoplasma infection and later development of schizophrenia in mothers. Am J Psychiatry. 2011;168(8):814–21. [PubMed]
66. Jones-Brando L, Torrey EF, Yolken R. Drugs used in the treatment of schizophrenia and bipolar disorder inhibit the replication of Toxoplasma gondii . Schizophr Res. 2003;62:237–244. [PubMed]
67. Goodwin DG, Strobl J, Mitchell SM, Zajac AM, Lindsay DS. Evaluation of the mood-stabilizing agent valproic acid as a preventative for toxoplasmosis in mice and activity against tissue cysts in mice. J Parasitol. 2008;94:555–557. [PubMed]
68. Goodwin DG, Strobl JS, Lindsay DS. Evaluation of five antischizophrenic agents against Toxoplasma gondii in human cell cultures. J Parasitol. 2011;97:148–51. [PubMed]
69. Kar N, Misra B. Toxoplasma seropositivity and depression: a case report. BMC Psychiatry. 2004;4:1. [PMC free article] [PubMed]
70. National Institute of Mental Health. Obsessive-compulsive disorder, OCD. 2011. Available from:
71. Miman O, Kusbeci OY, Aktepe OC, Cetinkaya Z. The probable relation between Toxoplasma gondii and Parkinson's disease. Neuroscience Lett. 2010;475:129–131. [PubMed]
72. Brynska A, Tomaszewicz-Libudzic E, Wolanczyk T. Obsessive-compulsive disorder and acquired toxoplasmosis in two children. Eur Child Adolesc Psychiatry. 2001;10:200–204. [PubMed]
73. WHO. World report on violence and health; Geneva: World Health Organization; 2002.
74. Arling TA, Yolken RH, Lapidus M, Langenberg P, Dickerson FB, Zimmerman SA, Balis T, Cabassa JA, Scrandis DA, Tonelli LH, Postolache TT. Toxoplasma gondii antibody titers and history of suicide attempts in patients with recurrent mood disorders. J Nerv Mental Dis. 2009;197:905–908. [PubMed]
75. Yagmur F, Yazar S, Ozcan Temel H, Cavusoglu M. May Toxoplasma gondii increase suicide attempt-preliminary results in Turkish subjects? Forens Sci Int. 2010;199:15–17. [PubMed]
76. Ling VJ, Lester D, Mortensen PB, Langenberg PW, Postolache TT. Toxoplasma gondii seropositivity and suicide rates in women. J Nerv Ment Dis. 2011;199(7):440–4. [PMC free article] [PubMed]
77. WHO. Global status report on road safety; Geneva: World Health Organization; 2009.
78. Flegr J, Havlícek J, Kodym P, Malý M, Smahel Z. Increased risk of traffic accidents in subjects with latent toxoplasmosis: a retrospective case-control study. BMC Infect Dis. 2002;2:11. [PMC free article] [PubMed]
79. Yereli K, Balcioğlu IC, Ö zbilgin A. Is Toxoplasma gondii a potential risk for traffic accidents in Turkey? Forens Sci Int. 2006;163:34–37. [PubMed]
80. Kocazeybek B, Ali Oner Y, Turksoy R, Babur C, Cakan H, Sahip N, Unal A, Ozaslan A, Kılıc S, Saribas S, Aslan M, Taylan A, Koc S, Dirican A, Bulent Uner H, Oz V, Ertekin C, Kucukbasmaci O, Mamal Torun M. Higher prevalence of toxoplasmosis in victims of traffic accidents suggest increased risk of traffic accident in Toxoplasma-infected inhabitants of Istanbul and its suburbs. Forens Sci Int. 2009;187:103–108. [PubMed]
81. Flegr J, Klose J, Novotná M, Berenreitterová M, Havlíček J. Increased incidence of traffic accidents in Toxoplasma-infected military drivers and protective effect RhD molecule revealed by a large-scale prospective cohort study. BMC Infect Dis. 2009;9:72. [PMC free article] [PubMed]
82. Nussbaum RL, Ellis CE. Alzheimer's disease and Parkinson's disease. N Engl J Med. 2003;348:1356–1364. [PubMed]
83. Yilmaz KO, Ozlem M, Mehmet Y, Orhan Cem A, Suleyman Y. Could Toxoplasma gondii have any role in Alzheimer disease? Alzheimer Dis Assoc Disorder. 2011;25:1–3. [PubMed]
84. Miman O, Kusbeci OY, Aktepe OC, Cetinkaya Z. The probable relation between Toxoplasma gondii and Parkinson's disease. Neuroscience Lett. 2010;475:129–131. [PubMed]
85. Celik T, Kamişli O, Babür C, Cevik MO, Oztuna D, Altinayar S. Is there a relationship between Toxoplasma gondii infection and idiopathic Parkinson's disease? Scand J Infect Dis. 2010;42:604–8. [PubMed]
86. Sander JW. The epidemiology of epilepsy revisited. Curr Opin Neurol. 2003;16:165–70. [PubMed]
87. Preux PM, Druet-Cabanac M. Epidemiology and etiology of epilepsy in sub-Saharan Africa. Lancet Neurol. 2005;4:21–31. [PubMed]
88. Stommel EW, Seguin R, Thadani VM, Schwartzman JD, Gilbert K, Ryan KA, Tosteson TD, Kasper LH. Cryptogenic epilepsy: An infectious etiology? Epilepsia. 2001;42:436–438. [PubMed]
89. Yazar S, Arman F, Yalcin S, Demirtas F, Yaman O, Sahin I. Investigation of probable relationship between Toxoplasma gondii and cryptogenic epilepsy. Seizure. 2003;12:107–109. [PubMed]
90. Akyol A, Bicerol B, Ertug S, Ertabaklar H. Epilepsy and seropositivity rates of Toxocara canis and Toxoplasma gondii . Seizure. 2007;16:233–237. [PubMed]
91. Koseoglu E, Yazar S, Koc I. Is Toxoplasma gondii a causal agent in migraine? Am J Med Sci. 2009;338:120–122. [PubMed]
92. Palmer BS. Meta-analysis of three case controlled studies and an ecological study into the link between cryptogenic epilepsy and chronic toxoplasmosis infection. Seizure. 2007;16:657–663. [PubMed]
93. Vasconcelos MM. Mental retardation. J Pediatr (Rio J) 2004;80(2):S71–82. [PubMed]
94. Stern H, Booth JC, Elek SD, Fleck DG. Microbial causes of mental retardation the role of prenatal infections with cytomegalovirus, rubella virus, and Toxoplasma . Lancet. 1969;294:443–448. [PubMed]
95. Alford CA, Stagno S, Reynolds DW. Congenital toxoplasmosis: clinical, laboratory and therapeutic considerations, with special reference to subclincial disease. Bull NY Acad Med. 1974;50:160–181. [PubMed]
96. Caiaffa WT, Chiari CA, Figueiredo RP, Orefice F, Antunes CM. Toxoplasmosis and mental retardation-report of a case-control study. Mem Inst Oswaldo Cruze. 1993;88:253–261. [PubMed]
97. Kaňková Š, Kodym P, Frynta D, Vavrinova R, Kubena A, Flegr J. Influence of latent toxoplasmosis on the secondary sex ratio in mice. Parasitology. 2007;134:1709–1717. [PubMed]
98. Kaňková Š, Šulc J, Nouzová K, Fajfrlík K, Frynta D, Flegr J. Women infected with parasite Toxoplasma have more sons. Naturwissenschaften. 2007;94:122–127. [PubMed]
99. Kaňková Š, Holáň V, Zajícová A, Kodym P, Flegr J. Modulation of immunity in mice with latent toxoplasmosis—the experimental support for the immunosuppression hypothesis of Toxoplasma-induced changes in reproduction of mice and humans. Parasitol Res. 2010;107:1421–1427. [PubMed]
100. Xiao J, Jones-Brando L, Talbot CC, Yolken RH. Differential effects of three canonical Toxoplasma strains on gene expression in human neuroepithelial cells. Infect Immun. 2011;79:1363–1373. [PMC free article] [PubMed]
101. Hermes G, Ajioka JW, Kelly KA, Mui E, Roberts F, Kasza K, Mayr T, Kirisits MJ, Wollmann R, Ferguson DJ, Roberts CW, Hwang JH, Trendler T, Kennan RP, Suzuki Y, Reardon C, Hickey WF, Chen L, McLeod R. Neurological and behavioral abnormalities, ventricular dilatation, altered cellular functions, inflammation, and neuronal injury in brains of mice due to common, persistent, parasitic infection. J Neuroinflammation. 2008;5:48. [PMC free article] [PubMed]
102. Stibbs HH. Changes in brain concentration of catecholamines and indoleamines in Toxoplasma gondii infected mice. Annal Trop Med Parasitol. 1985;79:153–157. [PubMed]
103. Laakso MP, Soininen H, Partanen K, Helkala EL, Hartikainen P, Vainio P, Hallikainen M, Hänninen T, Riekkinen PJ. Volumes of hippocampus, amygdala and frontal lobes in the MRI-based diagnosis of early Alzheimer's disease: Correlation with memory functions. J Neural Transmission. 1995;9:73–86. [PubMed]
104. Horna R, Ostertunb B, Frica M, Solymosib L, Steudelb A, Möllera HJ. Atrophy of hippocampus in patients with Alzheimer's disease and other diseases with memory impairment. Dementia. 1996;7:182–186. [PubMed]
105. Shenton ME, Gerig G, McCarley RW, Székely G, Kikinis R. Amygdala-hippocampal shape differences in schizophrenia: the application of 3D shape models to volumetric MR data. Psychiatry Res. 2002;115(1-2):15–35. [PMC free article] [PubMed]
106. Bogerts B, Lieberman JA, Ashtari M, Bilder RM, Degreef G, Lerner G, Johns C, Masiar S. Hippocampus-amygdala volumes and psychopathology in chronic schizophrenia. Biol Psychiatry. 1993;33:236–246. [PubMed]
107. Mervaala E, Föhr J, Könönen M, Valkonen-Korhonen M, Vainio P, Partanen K, Partanen J, Tiihonen J, Viinamäki H, Karjalainen AK, Lehtonen J. Quantitative MRI of the hippocampus and amygdala in severe depression. Psychol Med. 2000;30:117–25. [PubMed]
108. Tanskanen P, Veijola HM, Piippo UK, Haapea M, Miettunen JA, Pyhtinen J, Bullmore ET, Jones PB, Isohanni MK. Hippocampus and amygdala volumes in schizophrenia and other psychoses in the Northern Finland 1966 birth cohort. Schizophr Res. 2005;75:283–294. [PubMed]
109. Tebartz van Elst L, Baeumer D, Lemieux L, Woermann FG, Koepp M, Krishnamoorthy S, Thompson PJ, Ebert D, Trimble MR. Amygdala pathology in psychosis of epilepsy A magnetic resonance imaging study in patients with temporal lobe epilepsy. Brain. 2001;25:140–149. [PubMed]
110. Taupin P. The hippocampus neurotransmission and plasticity in the nervous system. Nova Science Publishers; 2007.
111. Baxter MG, Murray EA. The amygdala and reward. Nat Rev Neuroscience. 2002;3:563–573. [PubMed]
112. Davis KL, Kahn KS, Ko G, Davidson M. Dopamine in schizophrenia: a review and reconceptualization. Am J Psychiatry. 1991;148:1474–1486. [PubMed]
113. Wolfe N, Katz ID, Albert ML, Almozlino A, Durso R, Smith MC, Volicer L. Neuropsychological profile linked to low dopamine: in Alzheimer's disease, major depression, and Parkinson's disease. J Neurol Neurosurg Psychiatry. 1990;53:915–917. [PMC free article] [PubMed]
114. Chan-Palay V, Asan E. Alterations in catecholamine neurons of the locus coeruleus in senile dementia of the Alzheimer type and in Parkinson's disease with and without dementia and depression. J Comarat Nuerol. 1989;287:373–392. [PubMed]
115. Skallova A, Kodym P, Frynta D, Flegr J. The role of dopamine in Toxoplasma induce behavioural alterations in mice: an ethological and ethopharmacological study. Parasitology. 2006;133:525–535. [PubMed]
116. Webster JP, Lamberton PHL, Donnelly CA, Torrey EF. Parasites as causative agents of human affective disorders? The impact of anti-psychotic, mood-stabilizer and anti-parasite medication on Toxoplasma gondii's ability to alter host behaviour. Proc R Soc B. 2006;273:1023–1030. [PMC free article] [PubMed]
117. Gaskell EA, Smith JE, Pinney JW, Westhead DR, McConkey GA. A unique dual activity amino acid hydroxylase in Toxoplasma gondii . PLoS ONE. 2009;4(3):e4801. doi: 10.1371/journal.pone.0004801. [PMC free article] [PubMed] [Cross Ref]
118. Müller M. Immunological and infectious aspects of schizophrenia. Eur Arch Psychiatry Clin Neurosci. 2004;254:1–3. [PubMed]
119. Müller N, Schwarz MJ. Immune system and schizophrenia. Curr Immunol Rev. 2010;6:213–220. [PMC free article] [PubMed]
120. Miller CM, Boulter NR, Ikin RJ, Smith NC. The immunobiology of the innate response to Toxoplasma gondii . Int J Parasitol. 2009;39:23–39. [PubMed]
121. Brown AS, Hooton J, Schaefer CA, Zhang H, Petkova E, Babulas V, Perrin M, Gorman JM, Susser ES. Elevated maternal interleukin-8 levels and risk of schizophrenia in adult offspring. Am J Psychiatry. 2004;161:889–895. [PubMed]
122. Buka SL, Tsuang MT, Torrey EF, Klebanoff MA, Wagner RL, Yolken RH. Maternal cytokine levels during pregnancy and adult psychosis. Brain Behav Immun. 2001;15:411–420. [PubMed]
123. Rostami Nejad M, Jahani Sherafat S, Roshani M, Telkabadi M, Lahmi F, Cheraghipour K, Kaboli AR, Alavi-Moghaddam M. The evaluation of interleukin-8 chemokine in chronic and acute Toxoplasma gondii infection. Gastroenterol Hepatol Bed Bench. 2011;4(1):34–37. [PMC free article] [PubMed]
124. Jue CH, Chockalingam A, Leifer CA. Early response of mucosal epithelial cells during Toxoplasma gondii infection. J Immunol. 2009;183:7420–7. [PMC free article] [PubMed]
125. Cazzullo CL, Scarone S, Grassi B, Vismara C, Trabattoni D, Clerici M, Clerici M. Cytokines production in chronic schizophrenia patients with or without paranoid behaviour. Prog Neuropsychopharmacol Biol Psychiatry. 1998;22:947–957. [PubMed]
126. Maes M, Bosmans E, Calabrese J, Smith R, Meltzer HY. Interleukin-2 and interleukin-6 in schizophrenia and mania: Effects of neuroleptics and mood stabilizers. J Psychiatric Res. 1995;29:141–152. [PubMed]
127. Ganguli R, Yang Z, Shurin G, Chengappa R, Brar JS, Gubbi AV, Rabin BS. Serum Interleukin-6 concentration in schizophrenia: elevation associated with duration of illness. Psychiatry Res. 1994;51:1–10. [PubMed]
128. Lin A, Kenis G, Bignotti S, Tura GJB, De Jong R, Bosmans E, Pioli R, Altamura C, Scharpé S, Maes M. The inflammatory response system in treatment-resistant schizophrenia: increased serum Interleukin-6. Schizophrenia Res. 1998;32:9–15. [PubMed]
129. Zhang XY, Zhou DF, Zhang PY, Wu GY, Cao LY, Shen YC. Elevated interleukin-2, interleukin-6 and interleukin-8 serum levels in neuroleptic-free schizophrenia: association with psychopathology. Schizophr Res. 2002;57:247–58. [PubMed]
130. Arolt V, Rothermundt M, Wandinger KP, Kirchner H. Decreased in vitro production of interferon-gamma and interleukin-2 in whole blood of patients with schizophrenia during treatment. Mol Psychiatry. 2000;5:150–158. [PubMed]
131. Zhang XY, Zhou DF, Cao LY, Zhang PY, Wu GY, Shen YC. Changes in serum interleukin-2, -6, and -8 levels before and during treatment with risperidone and haloperidol: relationship to outcome in schizophrenia. J Clin Psychiatry. 2004;65:940–7. [PubMed]
132. Jebbari H, Roberts CW, Ferguson DJ, Bluethmann H, Alexander J. A protective role for IL-6 during early infection with Toxoplasma gondii . Parasite Immunol. 1998;20:231–9. [PubMed]
133. Lahmar I, Abou-Bacar A, Abdelrahman T, Guinard M, Babba H, Ben Yahia S, Kairallah M, Speeg-Schatz C, Bourcier T, Sauer A, Villard O, Pfaff AW, Mousli M, Garweg JG, Candolfi E. Cytokine profiles in toxoplasmic and viral uveitis. J Infect Dis. 2009;199:1239–49. [PubMed]
134. Fischer HG, Nitzgen B, Reichmann G, Hadding U. Cytokine responses induced by Toxoplasma gondii in astrocytes and microglial cells. Eur J Immunol. 1997;27:1539–48. [PubMed]
135. Müller N, Riedel M, Ackenheil M, Schwarz MJ. Cellular and humoral immune system in schizophrenia: A conceptual re-evaluation. World J Biol Psychiatry. 2000;1:173–179. [PubMed]
136. Hama T, Kushima Y, Miyamoto M, Kubota M, Takei N, Hatanaka H. Interleukin-6 improves the survival of mesencephalic catecholaminergic and septal cholinergic neurons from postnatal, two-week-old rats in cultures. Neurosci. 1991;40:445–452. [PubMed]
137. Muller N, Schwarz M. Schizophrenia as an inflammation-mediated dysbalance of glutamatergic neurotransmission. Neurotoxicity Res. 2006;10:131–148. [PubMed]
138. Wonodi I, Schwarcz R. Cortical kynurenine pathway metabolism: A novel target for cognitive enhancement in schizophrenia. Schizophr Bull. 2010;36:211–218. [PMC free article] [PubMed]
139. Schwarcz R, Hunter CA. Toxoplasma gondii and schizophrenia: Linkage through astrocyte-derived kynurenic acid? Schizophr Bull. 2007;33:652–653. [PMC free article] [PubMed]
140. Nilsson LK, Linderholm KR, Engberg G, Paulson L, Blennow K, Lindström LH, Nordin C, Karanti A, Persson P, Erhardt S. Elevated levels of kynurenic acid in the cerebrospinal fluid of male patients with schizophrenia. Schizophr Res. 2005;80:315–322. [PubMed]
141. Erhardt S, Blennow K, Nordin C, Skogh E, Lindström LH, Engberg G. Kynurenic acid levels are elevated in the cerebrospinal fluid of patients with schizophrenia. Neurosci Lett. 2001;313:96–98. [PubMed]
142. Schwarcz R, Rassoulpour A, Wu HQ, Medoff D, Tamminga CA, Roberts RC. Increased cortical kynurenate content in schizophrenia. Biol Psychiatry. 2001;50:521–530. [PubMed]
143. Miller CM, Boulter NR, Ikin RJ, Smith NC. The immunobiology of the innate response to Toxoplasma gondii . Int J Parasitol. 2009;39:23–39. [PubMed]
144. Däubener W, Spors B, Hucke C, Adam R, Stins M, Kim KS, Schroten H. Restriction of Toxoplasma gondii growth in human brain microvascular endothelial cells by activation of indoleamine 2,3-dioxygenase. Infect Immun. 2001;69:6527–31. [PMC free article] [PubMed]
145. Wilson EH, Hunter CA. The role of astrocytes in the immunopathogenesis of toxoplasmic encephalitis. Int J Parasitol. 2004;34:543–8. [PubMed]

Articles from Iranian Journal of Parasitology are provided here courtesy of Tehran University of Medical Sciences