Effects T. gondii On Behavior and Psychiatric Symptoms
Beginning in the late 1970s, G. Piekarski (1978) and P.-A. Witting (1979) in Bonn began investigations to ascertain possible effects of latent T. gondii on mice and rats. The impetus for their research appears to have been the reported behavioral effects of other parasitic infections and the known association of congenital T. gondii with mental retardation. Piekarski and Witting reported that T. gondii caused impaired learning in mice and rats and impaired memory in mice. Based on these findings, Hutchinson, Hay et al. in Glasgow studied T. gondii –infected mice and reported that, compared to uninfected controls, the infected mice had impaired motor performance and increased activity, especially in exploring novel environments. Holliman summarized this early research.1 Much subsequent work has been carried out in rodents.2
Behavioral manipulation by T. gondii in animals
(see also section VI. Neurotransmitters and T. gondii)
The manipulation hypothesis states that a parasite may alter the behavior of its host in order to improve its transmission rate. Carl Zimmer’s Parasite Rex provides wonderful illustrations of this phenomenon.
Joanne Webster and her colleagues, initially at Oxford and now at Imperial College London, noted the early research cited above and carried it forward. Beginning in 1994, they published a series of studies demonstrating that rats infected with T. gondii were more active and less neophobic of cat urine than controls rats.3 Both changes would make it more likely that the rat would be eaten by a cat, thus completing the life cycle of T. gondii and being an example of the manipulation hypothesis. These studies were summarized by Dr. Webster.4 Webster and Glenn McConkey have also speculated about specific mechanisms that may explain the parasite manipulation.5-7
Given the findings of Webster et al., Ajai Vyas and his colleagues then at Stanford University sought to replicate them. They did so, showing in both mice and rats that T. gondii infection reverses the rodents’ natural aversion to the smell of cat urine and causes them to instead “develop an actual attraction to the pheromones”. 8 They also speculated regarding possible pathophysiological mechanisms9 and showed that one of the mechanisms used by T.gondii is to activate sexual arousal pathways of the rats10 Other research has suggested that T. gondii exerts its effect through epigenetic modulation of the host’s amygdala.11
Since these early demonstrations of the ability of T. gondii to manipulate behavior were carried out in rodents, the question of their relevance to humans remained. A study published in 2016 addressed this question. Normally chimpanzees are repelled by the scent of a leopard, which is a predator of chimps. In Gabon 33 chimps held in captivity were investigated regarding their reaction to leopard urine. The 24 chimps not infected with T. gondii demonstrated the expected aversion to the leopard urine but the 9 chimps infected with T. gondii did not. The reactions were specific to leopard urine and not for lion or tiger urine, neither of which is a natural predator of chimps since they don’t live in the rainforest where chimps live. Since T. gondii can manipulate the behavior of chimpanzees, it seems likely that it can also manipulate the behavior of humans.12
As suggested by the above findings, there is evidence that the effects of T. gondii on the brain are highly specific. For example, in experiments in which mice have been infected, the mice may have profound and widespread brain pathology and deficits in motor coordination and sensory deficits, but their cognitive skills remain relatively intact13. It has also been shown that the effects of T. gondii in rodents is sex specific as assessed by gene expression. A study of this specificity concluded that “the sex of the host plays a major role in determining variable brain and behavior changes following Toxoplasma infection”.14
Another interesting example of the effects of T. gondii on animal behavior is the sea otters who live off the coast of California. Many have become infected with T. gondii, presumably because of rainwater runoff from cat-infested areas carrying the oocysts into the ocean. A 2004 study reported that sea otters with toxoplasmosis were 3.7 times more likely to be attacked by sharks than others who were not infected.15
In 2018 another unexpected effect of T. gondii on human behavior was reported. College students who were seropositive were 1.4 times more likely to major in business than those who were seronegative. Among business professionals those who were seropositive were 1.8 times more likely to have started their own business.81
Effects of T. gondii on personality traits of humans
Jaroslav Flegr and his colleagues at Charles University in Prague have, since 1992, been studying the effects of T. gondii infection on human personality traits and behavior. Utilizing university students, military recruits, and blood donors, Flegr et al. have administered a series of personality questionnaires and compared individuals with and without antibodies to T. gondii. Infected men were shown to be more expedient, suspicious, jealous, and dogmatic, whereas infected women had more warmth and superego strength. Thus, sex differences of the effect of T. gondii in humans have been shown, just as they have been in rodents. Flegr has summarized these findings.16-17 An article describing Flegr’s research was also published in the Atlantic magazine.18 In a separate study T. gondii infection was associated with increased aggressive traits in women but not in men.19
Effects of T. gondii on cognition in humans
The effect of T. gondii on human cognition was initially noted in 1947 by Eichenwald reported mental retardation to be one outcome of severe congenital toxoplasmosis20. Following the 1947 report, additional studies were undertaken to assess the prevalence of antibodies to T. gondii in individuals with moderate and severe retardation. Many, but not all such studies were negative although these older studies used antibody measurements of varying sensitivity and the control groups were often poorly matched.21-22
Beginning in the 1970s, researchers initiated long-term follow-up studies of individuals with serological evidence of having been infected with T. gondii in utero, the majority of whom had no clinical manifestation at birth. A 20-year follow-up of 12 children in the Netherlands reported no major effects on intelligence, although several children had developed progressive chorioretinitis.23 An ongoing American study of 120 children with congenital toxoplasmosis who were treated for one year with anti-toxoplasmosis drugs has also reported no significant drop in IQ scores24. Of concern, however, was a subset of these children who had IQ scores within a normal range but which were significantly lower than their sibling controls.25 In another large American study of children born to women infected with T. gondii during pregnancy, the children of the women with the highest titres had delayed mental development in their first year and an increased risk of having an IQ less than 70 at 7 years.26 In summary, regarding the effect of toxoplasmosis on IQ, the statement by Remington, et al in 2001 appears to still be applicable: “The total contribution of congenital toxoplasmosis, including the less severe and clinically unapparent forms at birth, to mental retardation is uncertain”20 (p. 255).
In addition to congenital infections with T. gondii, postnatal infections may also affect human cognition and behavior. Two recent studies were carried out on schoolchildren. In Brazil 100 children ages 6-13 were tested for T. gondii antibodies and the results compared to their test results for reading, writing, and mathematics. Toxopositive children had a higher proportion of poor results on the mathematics subtest (p=0.009) but not on the other tests27. In Florida, 1,755 schoolchildren were tested for T. gondii antibodies and given a series of cognitive tests. Seropositivity was associated with lower reading skills (p=0.029) and memory capacities (p=0.017).28
Six studies, all published since 2014, have reported on cognitive effects of toxoplasma seropositivity in adults. A study of 352 adults with a mean age of 32.2 years, being used as healthy controls in a psychiatric study, reported an association between toxo IgM, but not IgG, and impaired immediate memory (p=0.04); language (p=0.004); and visuospatial construction (p=0.001)29. Another study of 180 adults with a mean age of 40.1, also being used as healthy controls in a psychiatric study, reported an effect of T. gondii on working memory.30
Four studies of older adults have all reported associations between toxo IgG positivity and cognitive problems. Eighty four volunteer adults with a mean age of 70.3 were divided into groups of 42 toxo IgG positive and negative. The toxo positive group showed significant impairment in working memory and verbal memory, both immediate and delayed recall, executive function were not affected.31.In a subset of this same cohort the toxo positive group displayed significant impairment in goal-directed behavior as assessed by an auditory distraction paradigm.32 Among 4,485 participants, mean age 69, in a national nutrition survey, toxo IgG seropositivity was associated with impairment of immediate memory (p=0.006) but not delayed memory.33 Finally, among 1,022 participants, mean age 77.5, in a longitudinal random population sample, toxo IgG seropositivity was significantly associated with a more rapid decline in executive function but not in decline of attention, memory, language or visuospatial function.34 However, a fifth study of 114 nondemented older adults reported “little evidence of an association between impaired memory function and T. gondii seropositivity.35
Effects of T. gondii on reaction time and vehicular homicides
In 1979 Hutchinson in Glasgow reported that infection with T. gondii impaired the motor performance of mice. In 2001 Havlicek et al in Prague compared T. gondii infected and uninfected human subjects on reaction time as measured by a standard computerized test. Infected individuals performed significantly more poorly and appeared to lose their concentration more quickly.36 Pearce et al., also demonstrated psychomotor slowing in healthy humans, as well as those with schizophrenia, who were infected with T. gondii compared with those not infected.37
Based on such findings, Flegr et al. in Prague wondered whether a delayed reaction time caused by a T. gondii infection might interfere with people’s ability to drive vehicles. He therefore compared the sera of 146 individuals deemed to have been responsible for causing a motor vehicle accident38, with 446 controls. Those individuals who had antibodies to T. gondii, compared with those without antibodies, had more than twice the risk of having caused a motor vehicle accident. Since that time there have been 9 attempts to replicate these findings, as summarized on the table. Five of the studies reported a statistically significant increase in T. gondii seropositivity among drivers involved in vehicular accidents compared to controls.40,41,80,90,92 Two other studies did not find a significant increase in seropositivity but did find a significant increase in T. gondii IgG mean titres in the accident group.89,91 Two studies were negative.39,88
In view of this association between traffic accidents and T. gondii, researchers in Mexico assessed the T. gondii antibody status in 133 individuals involved in work-related industrial accidents and 266 controls. Overall there was no association except among workers who had low socioecononomic status.42
|Country, Author and Year||Cases||Controls||Results|
Flegr, et al
|146 drivers who caused accident or pedestrians hit by vehicle, all injured||446 local residents from serological surveys||OR 2.65 (95% C.I 1.76-4.01)
Yereli, et al
|185 drivers involved in accidents, taken to ER.
Blood alcohol negative
|185 residents of same region, age and sex matched||cases 32% +;
controls 9% +
OR 5.07 (95% CI 2.69-9.65)
Kocazeybsk et al
|243 drivers involved in accidents (25 fatal), taken to ER. Blood alcohol negative.||200 blood donors, age and sex matched||cases 54% +
controls 28% +
OR 2.96 (95% CI 1.98-4.40)
Flegr, et al
|111 military recruits who had traffic accidents according to military records||3,7779 recruits with no accident on record||cases 25% +
controls 23% +
Samojlowicz et al
|42 drivers of cars, motorcycles or bikes in accident||86 people who died from disease, homicide, or as passengers in accident||cases 60%+
controls 49% +
Galvan-Ramirez et al
|159 drivers involved in accidents, taken to ER
|164 drivers who had never been in accidents||cases 34% +
controls 36% +
mean IgG titres higher in cases than controls; p = 0.01
Khadervatan et al
|103 drivers involved in accidents. Alcohol negative||200 residents of same city||cases 37%+
OR 2.02 (95% CI 1.73-3.33)
Shotar et al
|13 drivers arrested for being in accidents||200 “from normal population”||cases 15% +
controls 12% +
mean IgG titres higher in cases than controls
Stepanova et al
|100 drivers hosptialized for an accident for which they were responsible. Alcohol negative||152 people undergoing routine medical examinations||cases 45% +
controls 26% +
OR 2.37 (95% CI 1.34-4.2)
Burgdorf et al
|2,724 drivers in accidents from national register||6,294 matched controls blood donors||OR 1.11 (95% CI 1.00-1.23)
Psychiatric manifestations of congenital T. gondii infections
It is clearly established that congenital infections with T. gondii, especially early in pregnancy, can produce intracranial calcifications, mental retardation, deafness, seizures, and retinal damage. Less clearly established are the long-term effects of congenital infection that occur late in pregnancy and that are often latent at birth. Two research groups have reported late effects, especially lower IQ, following latent congenital infections.43-44 However, long-term follow-up of a similar cohort in Europe reported no loss of IQ or other significant sequelae.45
No study has reported psychosis or other symptoms of schizophrenia in children infected with congenital latent toxoplasmosis. Rima McLeod, who has followed large numbers of such children over many years, reported that among the congenitally-infected cases “there have been only rare persons with these neuropsychiatric or other disease”.46 However, a 30-year psychiatric follow-up of the European cohort cited above reported one case of major depression, one suicide, and one case of sex change among the eight cases on which clinical data were available.47
Psychiatric manifestations of adult T. gondii infections
Humans may become infected with T. gondii at any time in life. In immunocompetent individuals, the infection is asymptomatic 90 percent of the time. In the other 10 percent, the “primary infections cause a mild, mononucleosis-like illness with low-grade fever, malaise, headache, and cervical lymphadenopathy”48. The clinical picture is nonspecific but often includes headache, fever, malaise, myalgia, and lymphadenopathy.49-50 In recent years, most clinical cases have been described in patients with AIDS, thus making it difficult to ascertain which clinical symptoms are due to the toxoplasmosis and which are due to AIDS. However, in 1966, prior the AIDS epidemic, two publications summarized the neurological and psychiatric symptoms found in T. gondii infection occurring in adults.
Kramer in the Netherlands summarized 114 cases of symptomatic adult toxoplasmosis published between 1940 and 1964. Among these, he noted that “psychiatric disturbances were very frequent,” occurring in 24 cases. Some cases were described as having acute or subacute psychosis, and others as having “psychic alteration”.51 Ladee et al., also in the Netherlands, noted that “the literature not infrequently focuses attention on psychoses with schizophrenic or schizophreniform features that accompany chronic toxoplasmosis or that acquired in childhood or early in adult life. . . . In several instances a neurasthenic prodromal stage is followed by an initially suspected paranoid or paranoid-hallucinatory picture”.52
Many of these early reported cases are very interesting. For example, in 1951 Ström reported two cases of adult toxoplasmosis in laboratory workers. A 22-year-old woman who “often pipetted toxoplasma exudates” developed lyphadenopathy, headache, and fever. Diagnosis of toxoplasmosis was confirmed by skin test. Attempts to demonstrate T. gondii by microscopy of CSF or inoculation of CSF into mice was unsuccessful. She also had psychiatric symptoms: three months after the onset of infection, she “finds it difficult to concentrate,” “cannot follow a conversation when several people are present,” and “she feels far away, as if her body wasn’t there”.53
In another case, a 47-year-old woman who also worked in the laboratory with T. gondii presented “obviously delirious with delusions and hallucinations . . . the patients was irrational, spoke frequently to imaginary characters in the room and indicated she was going to die from toxoplasmosis.” In fact, she went into a coma and did die, and her diagnosis was confirmed at autopsy by animal inoculation of brain, liver, and spleen. Despite a normal CSF (no cells, normal protein and sugar), it was also positive for T. gondii by animal inoculation.54
Since 1966, there have been occasional similar case reports, but except for patients with AIDS in whom psychiatric symptoms are prominent, this subject has received little attention. An example of a case report was a 20-year-old male who presented with delusions, auditory hallucinations, and catatonic symptoms but was then diagnosed with toxoplasmic encephalitis based on serological tests.55 The incidence of such cases is unknown.
Another possible psychiatric manifestation of T. gondii infection in immunocompetent hosts is suicidal ideation. One study in the United States assessed T. gondii antibodies in 99 individuals who had made a suicide attempt; 119 individuals with a recurrent mood disorder but no history of suicide attempts; and 39 unaffected controls. There was no significant difference in T. gondii seropositivity, but those who had attempted suicide had higher T. gondii antibody titres (p=0.004).56 A recent study of 156 suicide attempters and 127 controls in Mexico reported similar results. There was no statistical difference in seropositivity but the titers of the T. gondii antibody was significantly higher (p=0.04) in the suicide attempters.57 The association between suicide attempts and higher titre to T. gondii antibodies was replicated by a study in Turkey.58 A third study reported an association between suicide attempts and T. gondii seropositivity in patients with schizophrenia, but the association was only significant in younger patients.59 In 2012 a Danish study reported that women who were infected with T.gondii were significantly more likely to be suicidal and twice as likely to successfully commit suicide, compared to women not infected60 and in Sweden, a study of 54 adult suicide attempters reported increased seropositivity of T. gondii (OR 7.12, p=0.08) compared to controls61. Finally, a study of national suicide rates in 17 European nations reported a significant association between the prevalence of T. gondii and the suicide rate.62
Several other studies are of interests regarding the effect of T. gondii on behavior and psychiatric symptoms. Holub and his colleagues in Prague divided individuals with schizophrenia into those with antibodies to T. gondii (n=57) and those without such antibodies (n=194), then retrospectively assessed their clinical histories. The patients with antibodies were found to have had an earlier onset of their illness for men, but not women; to have more severe symptoms; and to have been hospitalized for longer.63 Seropositive patients with schizophrenia have also been reported to have more negative symptoms82,83, a continuous course,84 and to be treatment resistant.85
Another study of interest was the effect of seropositivity to T. gondii on the mortality rate of individuals with schizophrenia. In an earlier study, Dickerson et al. reported that antibodies for T. gondii were associated with an increased mortality.64 However, a later study reported that this relationship was no longer statistically significant when it was corrected for age and gender.65 Finally, a demographic study reported a correlation between the prevalence of T. gondii and the national homicide rate in 20 European nations for the year 2000.66
Another approach to this question is to do a follow-up examination of individuals who are thought to have been infected by T. gondii during outbreaks of water-borne infection. Examples of such outbreaks include a 1979 outbreak among 39 U.S. military personnel67 and a 1995 outbreak among an estimated 2,900–7,700 people in Victoria, Canada.68 To date, such follow-up studies have not been done.
The effects of different strains of T. gondii
Although at least 15 distinct strains of T. gondii are known, most isolates of T. gondii in Europe and North America belong to one of three strains: I, II, or III. Despite having more than 98 percent genetic identity, the effects of the three strains are quite different in rodents and are assumed to be so in humans as well. In mice, for example, the three strains produce significantly different gene expression.69 Studies of the three strains on gene expression in human neuroepithelial cells also show markedly different effects on gene expression, with type I exhibiting the highest level of gene expression.70 Rodent studies have also shown that immunity is strain specific; thus a person infected with one strain of T. gondii can become re-infected by a different strain.71
It has also been shown that different strains of T. gondii produce different effects on mouse behavior.72 Similarly, it is known that type I T. gondii is much more lethal in mice than type II or type III, but it was not known whether or not this also applies to human infections. A study from our laboratory suggests that type I T. gondii, compared to type II or III, is more likely to produce psychotic symptoms, especially for affective psychoses.73 Another study from our laboratory showed that the different strains of T. gondii had very different effects on neurotransmitters74 In a related study, in human congenital T. gondii infections, different strains of T. gondii were found to produce differences in the incidence of premature births and eye disease.75,77
The question remains “whether or not different strains of T. gondii are responsible for different disease manifestations in humans”.76 Two reviews of studies on this question both concluded that in humans different strains do indeed exhibit different virulence and cause different manifestations 86,87 For another review of this issue see Rico-Torres.78
- Holliman RE. Toxoplasmosis, behaviour and personality. J Infect. 1997;35:105–110.
- Kannan G, Pletnikov MV. Toxoplasma gondii and cognitive deficits in schizophrenia: An animal model perspective. Schizophr Bull. 2012;38:1155-61
- Berdoy M, Webster JP, Macdonald DW. Fatal attraction in rats infected with Toxoplasma gondii. Proc R Soc Lond B. 2000; 267: 1591–1594.
- Webster JP. Rats, cats, people and parasites: the impact of latent toxoplasmosis on behavior. Microbes Infect. 2001;3:1037–1045.
- Webster JP, McConkey GA. Toxoplasma gondii -altered behaviour: clues as to mechanism of action. Folia Parasitol. 2010;57:95–104.
- Webster JP, Kaushik M, Bristow GC, McConkey GA. Toxoplasma gondii infection, from predation to schizophrenia: can animal behavior help us understand human behavior? J Exp Biol. 2013;216:99-112.
- Kaushik M, Lamberton PHL, Webster JP. The role of parasites and pathogens in influencing generalized anxiety and predation-related fear in the mammalian central nervous system. Horm Behav. 2012;62:191-201.
- Vyas A, Kim S-K, Giacomini N, et al. Behavioral changes induced by Toxoplasma infection of rodents are highly specific to aversion of cat odors. Proc Natl Acad Sci USA. 2007;104:6442-6447, copyright 2007, the National Academy of Sciences of the USA; linked to PDF file with permission
- Vyas A, Sapolsky R. Manipulation of host behaviour by Toxoplasma gondii : what is the minimum a proposed proximate mechanism should explain? Folia Parasitol. 2010;57:88–94.
- House PK, Vyas A, Sapolsky R. Predator cat odors activate sexual arousal pathways in brains of Toxoplasma gondii infected rats. PLoS One. 2011;6:e23277.
- Hari Dass SA & Vyas A. Toxoplasma gondii infection reduces predator aversion in rats through epigenetic modulation in the host medial amygdala. Mol Ecol. 2014; 23(24): 6114-22).
- Poirotte C, et al. Morbid attraction in leopard urine in Toxoplasma infected chimpanzees. Current Biology. 2016; 26: R83-R101.
- Gulinello M, Acquarone M, Kim JH, et al., Acquired infection with Toxoplasma gondiiin adult mice results in sensorimotor deficits but normal cognitive behavior despite widespread brain pathology. Microbes Infect. 2010;12:528-537.
- Xiao J, Kannan G, Jones-Brando L, et al. Sex-specific changes in gene expression and behavior induced by chronic Toxoplasma infection in mice. Neuroscience. 2012;206:39-48.
- Miller MA, Grigg ME, Kreuder C, et al. An unusual genotype of Toxoplasma gondii is common in California sea otters (Enhydra lutris nereis) and is a cause of mortality. Int J Parasitol. 2004;34:275-84.
- Flegr J. Effects of Toxoplasma on human behavior. Schizophr Bull. 2007; 33: 757–760.
- Flegr J. Influence of latent toxoplasmosis on the phenotype of intermediate hosts. Folia Parasitol. 2010;57:81–87.
- McAuliff K. How your cat is making you crazy. The Atlantic. March 2012.
- Cook TB, et al. “Latent” infection with Toxoplasma gondii: Association with trait aggression and impulsivity in healthy adults. Journal of Psychiatric Research. 2015; 60: 87-94.
- Remington JS, et al. Toxoplasmosis. In Remington JS and Klein JO (eds), Infectious Diseases of the Fetus and Newborn Infant, 5th (Philadelphia: Saunders) 2001.
- Mackie MJ, Fiscus AG, Pallister P. A study to determine causal relationships of toxoplasmosis to mental retardation. Am J Epidemiology 1971; 94: 215-221.
- Robertson JS. Toxoplasmin sensitivity: subnormality and environment. J Hyg Camp. 1966; 64: 405-410.
- Koppe JG, Loewer-Sieger DH, Roever-Bonnet H. Results of 20 year follow-up of congenital toxoplasmosis. The Lancet. 1980; Feb: 254-256.
- Mcleod R., Boyer K, Karrison, T., et al. Outcome of Treatment for Congenital Toxoplasmosis, 1981-2004: The National Collaborative Chicago-based, Congenital Toxoplasmosis Study. 2006. Clin Infect Dis 42: 1383-94.
- Roizen N, et al. Neurological and developmental outcome in treated congenital toxoplasmosis. Pediatrics 1995; 95: 11-20.
- Sever JL, et al. Toxoplasmosis: maternal and pediatric findings in 23,000 pregnancies. Pediatrics 1988; 82: 181-92.
- Ferriera EC, et al. Association between seropositivity for Toxoplasmsa gondii, scholastic development of children, and risk factors for T. gondii infection. Trans R Soc Trop Med Hyg 2013; DOI: 10.1093/trstmh/trt026.
- Mandy A, et al. Toxoplasma gondii seropositivity and cognitive functions in school-aged children. Parasitology 2015; 142: 1221-1227.
- Dickerson F, Stallings C, Origoni A, et al. Antibodies to Toxoplasma gondii and cognitive functioning in schizophrenia, bipolar disorder, and nonpsychiatric controls. The Journal of Nervous and Mental Disease. 2014; 202: 589-593.
- Hamdani N, Daban-Huard C, Godin O, et al. Effects of cumulative Herpsviridae and Toxoplasma gondii infections on cognitive function in healthy, bipolar and schizophrenia subjects. 2017. J Clin Psychiatry 78: 18-26.
- Gajewski PD, et al. Toxoplasma gondii impairs memory in infected seniors. Brain, Behavior and Immunity. 2014; 36: 193-199.
- Bestse C, et al. Latent Toxoplasma gondii infection leads to deficits in goal-directed behavior in healthy elderly. Neurobiology of Aging. 2014; 35: 1037-1044.
- Mendy A, et al. Immediate rather than delayed memory impairment in older adults with latent toxoplasmosis. Brain, Behavior and Immunity
- Ningamaker VL, Yolken, RH, Tang T, et al. Temporal cognitive decline associated with exposure to infectious agents in a population-based, aging cohort. 2016. Alzheimer Dis Assoc Disord 30: 216-222.
- Wyman CP, Gale SD, Hedges-Muncy A, et al. Association between Toxoplasma gondii seropositivity and memory function in nondemented older adults. 2017. Neurobiology of Aging 53: 76-82.
- Havlicek J, Gasova Z, Smith AP, et al. Decrease in psychomotor performance in subjects with latent ‘asymptomatic’ toxoplasmosis. Parasitology. 2001;122:515–520.
- Pearce BD, Hubbard S, Rivera HN, et al. Toxoplasma gondii exposure affects neural processing speed as measured by acoustic startle latency in schizophrenia and controls. Schizophr Res. 2013; 150: 258-61.
- Flegr J, Havlicek J, Kodym P, et al. Increased risk of traffic accidents in subjects with latent toxoplasmosis: a retrospective case-control study. BMC Infect Dis. 2002;2:11.
- Flegr J, Klose J, Novotna M, et al. 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:e72.
- Yereli K, Balcioglu IC, Ozbilgin A. Is Toxoplasma gondii a potential risk for traffic accidents in Turkey? Forensic Sci Int. 2006;163:34–37.
- Kocazeybek B, Oner YA, Turksoy R, et al. Higher prevalence of toxoplasmosis in victims of traffic accidents suggest increased risk of traffic accident in Toxoplasma-infected inhabitants of Istanbul and its suburbs. Forensic Sci Int. 2009;187:103–108.
- Alvarado-Esquivel C, Torres-Castorena A, Liesenfeld O, et al. High seroprevalence of Toxoplasma gondii infection in a subset of Mexican patients with work accidents and low socioeconomic status. Parasites & Vectors. 2012;5:13.
- Alford A, Stagno S, Reynolds DW. Congenital toxoplasmosis: clinical, laboratory, and therapeutic considerations, with special reference to subclinical disease. Bull NY Acad Med. 1974; 50:160–181.
- Wilson CB, Remington JS, Stagno S, et al. Development of adverse sequelae in children born with subclinical congenital Toxoplasma Pediatrics. 1980;66:767–774.
- Koppe JG, Rothova A. Congenital toxoplasmosis: a long-term follow-up of 20 years. Int Ophthalmol. 1989;13:387–390.
- McLeod R, VanTubbergen C, Montoya JG, et al. Human toxoplasmosis infection. In LM Weiss and K Kim, eds., Toxoplasma gondii. Amsterdam: Elsevier; 2013:109.
- Selton J-P, Kahn RS. Schizophrenia after prenatal exposure to Toxoplasma gondii? Clin Infect Dis. 2002; 35:633–634.
- Kravetz JD. Toxoplasma gondii.In: Fratamico PM, Smith JL, Brogden KA, eds, Sequelae and Long-Term Consequences of Infectious Diseases. Washington, D.C.: ASM Press; 2009:217–228.
- Carme B, Demar M, Ajzenberg D, et al. Severe acquired toxoplasmosis caused by wild cycle of Toxoplasma gondii, French Guiana. Emerg Infect Dis. 2009;15:656-658.
- Silva CS, Neves ES, Benchimiol EL, et al. Postnatal acquired toxoplasmosis patients in an infectious disease reference center. Braz J Infect Dis. 2008;12:438-441.
- Kramer W. Frontiers of neurological diagnosis in acquired toxoplasmosis. Psychiatr Neurol Neurochir. 1966;69:43–64.
- Ladee GA, Scholten JM, Meyes FEP. Diagnostic problems in psychiatry with regard to acquired toxoplasmosis. Psychiatr Neurol Neurochir. 1966;69:65–82.
- Ström J. Toxoplasmosis due to laboratory infection in two adults. Acta Med Scand. 1951;139:244–252).
- Sexton RC, Eyles DE, Dillman RE. Adult toxoplasmosis. Am J Med. 1953;14:366–377.
- Freytag HW, Haas H. Psychiatric aspects of acquired toxoplasmosis. Nervenarzt. 1979;50:128–131, in German.
- Arling TA, Yolken RH, Lapidus M, et al.Toxoplasma gondii antibody titers and history of suicide attempts in patients with recurrent mood disorders. J Nerv Ment Dis. 2009;197:905–908.
- Alvarado-Esquivel C, Sánchez-Anguiano LF, Arnaud-Gil CA, et al. Toxoplasma gondii infection and suicide attempts: A case-control study in psychiatric outpatients. J Nerv Ment Dis. 2013;201:948-52.
- Yagmur F, Yazar S, Temel HO, et al. May Toxoplasma gondii increase suicide attempt-preliminary results in Turkish subjects? Forensic Sci Int. 2010;199:15-17.
- Okusaga O, Langenberg P, Sleemi A, et al. Toxoplasma gondii antibody titers and history of suicide attempts in patients with schizophrenia. Schizophr Res. 2011;133:150-155.
- Pedersen MG, Mortensen PB, Norgaard-Pedersen B, Postolache TT. Toxoplasma gondii infection and self-directed violence in mothers. Arch Gen Psychiatry. 2012; 69(11): 1123-1130.
- Zhang Y, Träskman-Bendz L, Janelidze S, et al. Toxoplasma gondii immunoglobulin G antibodies and nonfatal suicidal self-directed violence. J Clin Psychiatry. 2012;73:1069-76.
- Lester D. Predicting European suicide rates with physiological indices. Psychol Rep. 2010;107:713-4.
- Holub D, Flegr J, Dragomirecká E, et al. Differences in onset of disease and severity of psychopathology between toxoplasmosis-related and toxoplasmosis-unrelated schizophrenia. Acta Psychiatr Scand. 2013;127:227-38.
- 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;33:737-40.
- Dickerson F, Stallings C, Origoni A, Schroeder J, Khushalani S, Yolken R. Mortality in Schizophrenia: Clinical and Serological Predictors. Schizophr Bull. 2013 Aug 13.
- Lester D.Toxoplasma gondii and homicide. Psychol Rep. 2012;111:196-7.
- Benenson MW, Takafuji ET, Lemon SM, et al. Oocyst-transmitted toxoplasmosis associated with ingestion of contaminated water. N Engl J Med. 1982;307:666–669.
- Bowie WR, King AS, Werker DH, et al. Outbreak of toxoplasmosis associated with municipal drinking water. Lancet. 1997;350:173–177.
- Hill RD, Gouffon JS, Saxton AM, Su C. Differential gene expression in mice infected with distinct Toxoplasma strains. Infect Immun. 2012;80(3):968-74).
- Xiao J, Jones-Brando L, Talbot CC Jr, et al. Differential effects of three canonical Toxoplasmastrains on gene expression in human neuroepithelial cells. Infect Immun. 2011;79:1363–1373.
- Elbez-Rubinstein A, Ajzenberg, D, Darde M-L, et al. Congenital toxoplasmosis and reinfection during pregnancy: Case report, strain characterization, experimental model of reinfection, and review. 2009. Journal of Infectious Diseases 199: 280-5.
- Kannan G, Moldovan K, Xiao J-C, et al. Toxoplasma gondii strain-dependent effects on mouse behavior. Folia Parasitol. 2010;157:151–155; Xiao JC, Ye L, O’Donnell et al. Antigen burden is a critical determinant for behavioral and molecular abnormalities in mice with chronic Toxoplasma infections (International Toxoplasmosis Conference, Gettysburg, PA, June 2015.
- Xiao J, Buka SL, Cannon TD, et al. Serological pattern consistent with infection with type I Toxoplasma gondii in mothers and risk of psychosis among adult offspring. Microbes Infect. 2009;11:1011–1018.
- Xiao J, Li Y, Jones-Brando L, Yolken RH. Abnormalities of neurotransmitter and neuropeptide systems in human neuroepithelioma cells infected by three Toxoplasma strains. J Neural Transm. 2013;120:1631-9.
- McLeod R, Boyer KM, Lee D, et al. Prematurity and severity are associated with Toxoplasma gondii alleles (NCCCTS, 1981-2009). Clin Infect Dis. 2012;54:1595-605.
- Boothroyd JC and Grigg, ME. Population biology of Toxoplasma gondii and its relevance to human infection: do different strains cause different disease? Current Opinion in Microbiology. 2002, 5: 438-442.
- Shobab et al. Toxoplasma serotype is associated with development of ocular toxoplasmosis. J Infect Dis. 2013; 208: 1520-8.
- Rico-Torres CP, Vargas-Villavicencio JA and Correa D. Is Toxoplasma gondii type related to clinical outcome in human congenital infection? Systematic and critical review. Eur J Clin Microbiol Infect Dis. 2016: 35: 1079-1088.
- Gohardehi S, Sharif M, Sarvi S. et al. The potential risks of toxoplasmosis for traffic accidents: A systematic review and meta-analysis. Experimental Parasitology. 2018; 191: 19-24.
- Burgdorff KS, Trabjerg B, Pedersen MG, et al. Large-scale serology study of Toxoplasma and Cytomegalovirus in relation to psychiatric disorders, suicidal behavior and risk of traffic accidents. 2018. submitted.
- Johnson SK, Fitza MA, Lemer DA, et al. Risky business: linking Toxoplasma gondii infection and entrepreneurship behaviors across individuals and countries. Proc R Soc B. 2018. http://dx.doi.org/10.1098/rspb.2018.0822
- Fond G, Boyer L, Schurhoff F, et al. Latent toxoplasma infection in real-world schizophrenia: Results from the national FACE-SZ cohort. Schizophr Res 2018. doi: 10.1016/j.schres.2018.05.007
- Esshili A, Thabet S, Jemli A, et al. Toxoplasma gondii infection in schizophrenia and associated clinical features. Psychiatry Research 2016; 245: 327-332.
- Celik T, Kartalci S, Aytas O, et al. Association between latent toxoplasmosis and clinical course of schizophrenia–continuous course of the disease is characteristic for Toxoplasma gondii infected patients. Folia Parasitologica. 2015; 62: 015.
- Strac DC, et al. Increased prevalence of Toxoplasma gondii seropositivity in patients with treatment-resistant schizophrenia. Schizophr Res 2017; 193: 480-481.
- Xia J, Cheng, X-Y, Wang, X-J and Peng, H-J. Association between Toxoplasma gondii types and outcomes of human infection: a Meta-Analysis. Acta Microbiologica et Immunological Hungarica 2017. doi: 10.1556/030.64.2017.016.
- Xiao J and Yolken, RH. Strain hypothesis of Toxoplasma gondii infection on the outcome of human diseases. Acta Physiol (Oxf) 2015; 213: 828-45.
- Samoklowics D, et al. Prevalence of Toxoplasma gondii parasite infection among people who died due to sudden death in the capital city of Warsaw and its vicinity. Przegl Epidemiol 2013; 67: 29-33.
- Galvan-Ramirez M, Sanchez-Orozco, L, Rodriguez LR, et al. Seroepidemiology of Toxoplasma gondii infection in drivers involved in road traffic accidents in the metropolitan area of Guadalajara, Jalisco, Mexico. Parasites and Vectors. 2013; 6: 294.
- Khademvatan S, et al. The possible relationship of Toxoplasma with risk of traffic accidents. HealthMED. 2014; 8: 657-661.
- Shotar A, et al. Latent Toxoplasmosis and the involvement of road traffic accidents among a sample of Jordanian drivers. Research Journal of Medical Sciences. 2016; 10: 194-198.
- Stepanova E, et al. Significance of chronic toxoplasmosis in epidemiology of road traffic accidents in Russian federation. PloS One.2017. doi.dorg/10.1371/journal.pone.0184930.