The seroprevalence of antibodies to Toxoplasma gondii among children with autism
Erman Esnafoglu, Esra Yancar Demir, Yeliz Cetinkol, Mustafa Kerem Calgin, Abdullah Erdil, Emine Yurdakul Erturk, Abdullah Dagli
Article No: 4   Article Type :  Research
Objective: Although attempts have been made to explain the pathogenesis of autism spectrum disorders (ASD) with many factors such as genetic, immunological, environmental, and infectious agents, this mechanism remains for the most part unknown. Toxoplasma gondii is a parasite that is investigated in many psychiatric diseases. This work examines whether toxoplasmosis plays a role in the pathogenesis of ASD through a seroprevalence study.

Method: This study is based on a comparison of 102 children with ASD and 51 healthy children. In addition to routine laboratory tests, a sociodemographic form and a childhood autism rating scale were completed and the participants’ anti-toxoplasma IgM and IgG titers were requested.

Results: In 3 ASD children (2.9%) and in 1 control (2%), IgG positivity was identified. All subjects were negative for IgM. There was no statistically significant difference found between the two groups in terms of toxoplasma seropositivity.

Conclusion: Our data does not confirm the involvement of toxoplasmosis in the etiopathogenesis of ASD.
Keywords : Autism, autism spectrum disorder, toxoplasmosis, Toxoplasma Gondii
Dusunen Adam : The Journal of Psychiatry and Neurological Sciences : 2017;30:309-315
Full Text:


Autism spectrum disorder (ASD) is a disorder defined by incompetence for social interaction and communication and limited and repeated (stereotypic) behavior and interest that begins in the early stages of development (1). In recent epidemiologic studies, its estimated prevalence is about 1% (2,3). Assessed as a multifactorial disorder involving the interaction of neurologic, immunologic, environmental and genetic factors, the cause of autistic disorder is still not fully known (4).

Toxoplasma gondii (T. gondii) is an intracellular parasite affecting up to 30% of the global population (5). T. gondii has a high affinity to brain tissue. T. gondii may cause neuronal damage, affecting the hypothalamic-pituitary-adrenal functions and interacting with certain genes as well as affecting the synthesis of neurotransmitters like dopamine and serotonin (6). Toxoplasmosis has been investigated in the context of many psychiatric diseases such as schizophrenia, bipolar disorder, obsessive compulsive disorder, depression, anxiety disorder, personality changes, suicide, and even traffic accidents (7-18). The effect of a T. gondii infection in the early period of life occurs at the neurodevelopmental stage. Thus, children are particularly a high risk (19). As toxoplasma especially affects the central nervous system (CNS) initially, infection during childhood may cause neurodegeneration, resulting in the insufficient functioning of the CNS. Some authors found a higher rate of toxoplasma antibodies in children and adolescents struggling with education compared to normal children and adolescents of the same age, which supports this hypothesis (20). During its life cycle, T. gondii interacts with up to 3000 host genes and proteins, which may includes genes related to multiple sclerosis, Alzheimer’s and Parkinson’s Diseases, schizophrenia, bipolar disorder, depression, childhood obesity, attention deficit and hyperactivity disorder, and autism among others (21). It has been indicated that damage to areas of the brain such as the neocortex, limbic cortex and primitive striatal complex found in childhood autism may be caused by a variety of factors linked to toxoplasma (22). One of the effects of toxoplasma is that it causes an increase in dopamine which may affect human behavior and cause psychiatric diseases (23). There is also an increase in dopamine metabolism reported in ASD (25,26). In terms of neuropathological changes and clinical appearance, there are similarities between ASD and congenital and chronic latent toxoplasmosis. These similarities have led to the idea that T. gondii could be a significant infectious factor that may trigger the development of ASD, obsessive compulsive disorder, attention deficit-hyperactivity disorder, and some other neurodegenerative diseases like cryptogenic epilepsy (27). Additionally, latent toxoplasmosis is reactive to the effects of some environmental factors and has been suggested to result in the development of ASD (28). This study tested the hypothesis of a possible correlation between ASD and toxoplasmosis through seroprevalence research.


This case-control study was completed at the Pediatric and Adolescent Psychiatry, Pediatric and Microbiology Departments of Ordu University’s Faculty of Medicine, Training and Research Hospital from March 2015-March 2016. The study included 102 ASD patients (aged 3-16.5 years) and 51 healthy controls (aged 3.5-14 years). Children with ASD were recruited from the pediatric and adolescent psychiatry outpatient clinic. This hospital contains the only pediatric and adolescent psychiatric center in the region. Healthy children were recruited from the pediatric clinic and the pediatric psychiatric clinic of Ordu University Hospital with the condition of having either no psychiatric diagnosis or only minor diseases. Patients using antibiotics were excluded from the study due to the possibility of affecting toxoplasma seropositivity. Consent was obtained from the family of each participant. The study received permission from the Ordu University ethics committee.


Sociodemographic data included age, sex, residence, pregnancy, and birth history, onset of disease, medical history, family history, duration of breastfeeding, education, and medications used. The Childhood autism rating scale (CARS) consists of 15 items that are used to generate a total score defining the severity of autism. A total score between 30 and 36.5 indicates mild to moderate autism, whereas the interval between 37 and 60 denotes severe autism. CARS is scored by observing the child and through interviews conducted with the family (29).


As a result of detailed clinical observation and family interviews, 102 ASD children were diagnosed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders-5 (APA 2013). A general examination was performed for each participant by expert pediatricians. Additionally, all subjects completed the Childhood Autism Rating Scale (CARS) and a sociodemographic form, and routine laboratory and toxoplasma IgM and IgG values were requested.

Laboratory Assessment

Blood samples were taken from participants between 8 am and 11 am. On the same day, hemogram, routine biochemistry, thyroid function, and toxoplasma IgM and IgG antibodies were studied. Toxoplasma IgM and IgG were studied in patient and control serum using electrochemiluminescence immunoassay (ECLIA-Roche, Elecsys) according to the manufacturer’s instructions. Internal and external quality control of the kits was performed and recorded. Results were assessed as positive or negative. While assessing results, in accordance with the trade kit evaluation criteria for ECLIA-Roche, Elecsys Anti-T. gondii IgM values gt;1.0 S/CO values were positive and for anti-T. gondii IgG ≥3.0 IU/ml were positive.

Statistical Analysis

All statistical analyses were performed with SPSS 17.0 for Windows software (SPSS Inc., Chicago, IL, USA). According to the G power analysis results, in this study with 80% power and 5% type-1 error, when the expected rate in the control group is accepted as 4%, there must be at least 1861 subjects in each group for a 2% difference to be considered significant. Data are presented as the number of cases and percentage for categorical variables (seroprevalance, gender, etc.), and as the mean with standard deviation for ages and CARS values. The difference between the patient and control groups in terms of ages and CARS values was determined using the Student t-test. Chi-square and Fisher’s exact tests were applied to determine whether there was a relationship between IgG (negative and positive), gender, and group membership (control vs. patient). A p-value of lt;0.05 was considered statistically significant.


No statistically significant difference was found in terms of the ages between the patient group (7.63±3.46) and the control group (7.47±3.40) (p=0.784). However, a statistically significant difference was found in terms of the CARS values between the patient group (47.15±7.49) and the control group (15.0±0.00) (plt;0.001) (Table 1). There was no significant difference between the groups in terms of sex and IgG (p=0.118; p=0.593 respectively) (Table 2).

Of the IgG-positive ASD children, one was a 6.5-year-old male with a CARS score of 47 who used no medication, the second was a 10.5-year-old male with a CARS score of 32.5 who used only 40mg/day atomoxetine, and the third was a 16.5-year-old male with a CARS score of 48 who used multiple antipsychotic medication. In the control group, IgG positivity was observed in a 4-year-old male child with no medical or psychiatric diagnosis or medication use.


This study aimed to present serologic evidence showing the relationship between toxoplasmosis and autism. Serological research was applied to 154 subjects. Toxoplasmosis IgG positivity was 2.9% in the ASD group and 2% in the control group. This result indicates that there was no statistically significant difference between the autistic group and the healthy control group in terms of toxoplasma seropositivity. However, the risk was 1.98 times greater for IgG-positive individuals compared to IgG-negative individuals. Additionally, IgG positivity was identified only in males. Toxoplasma IgM was negative in all subjects. To the best of our knowledge, there are only two studies to date on this matter. The first seroprevalence study showed a correlation between toxoplasma and autism in Iran (30). The study examined 40 autistic children and 40 healthy controls. In the autistic group, all subjects were negative for IgM and IgG and in the control group only one child was positive for IgG. This study reached the same conclusion as our study, hence, it appears that both works are in agreement. The second study was completed by Prondota et al. (31). The results of that study found 23.9% of 46 autistic children to be IgG positive, while 4% of 50 control children were positive. There was a statistically significant difference between the two groups. This result contradicts with our findings. The age of the seropositive group was found to be greater than the seronegative group. Of the toxoplasma-positive children, 73% were male and 27% were female. The results by age and gender were similar to those of our study.

Toxoplasmosis is one of the most common infections globally. Epidemiological studies have estimated that nearly one third of the global population is infected (5). Epidemiologic studies in the US have found 22.5% IgG seropositivity, while the incidence increased with age (32). According to epidemiologic studies published in Turkish journals, the mean toxoplasma seropositivity in Turkey is between 23%-35.5% (33-35). Here, too, seropositivity was found to increase with age. A study on children in Turkey found IgG positivity at a level of 8.4% and IgM positivity of 0.4% (36). Our study found that positivity to lower than the mean for general society; however, the risk grows with increasing age. Apart from one subject (an Iraqi refugee), all subjects were from similar sociocultural backgrounds and residential areas. One of the reasons for low seropositivity may be that in this region of Turkey pet ownership traditionally is not common and the subjects do not live on farms and have no exposure to livestock. The negative IgM result for all subjects leads to the consideration that primary or reactivated toxoplasmosis does not play a role in autism pathogenesis. IgG positivity was only identified in males. Autism is observed more frequently in males; the male/female ratio is reported to be 4:1 (37). It has been proposed that high testosterone levels may contribute to the etiology of ASD in males with latent toxoplasmosis (38,39).

Another reason for low IgG positivity may be that some of the subjects in the autistic patient group used antipsychotics and valproate. Antipsychotic treatment has been identified to reduce antibody levels in schizophrenic patients (40). Additionally, an in vitro study found that antipsychotic medications and valproate inhibited the replication of toxoplasma (41). In the autism patient group, 48.5% (n=50) used antipsychotics. Additionally, while only 1 patient was taking valproate on its own, 4 were taking antipsychotics with valproate. Another reason that may explain the seronegativity is that all the Ig tests may not be sensitive and specific. As explained in an article by Prandota, reduced activation of lymphocyte B cells secreting immunoglobulin due to T. gondii infection, reduced immunoglobulins or autoimmune excessive immunoglobulin production linked to exhausted immune response to T. gondii may cause more IgG negativity (31).

Among the limitations of our study, there are the low seropositivity results and the small sample size. The small number of participants and the resulting low fraction of T. gondii seropositive individuals observed translate to a reduction in power to detect any underlying associations. Another limitation of this study was that only one child and adolescent psychiatrist diagnosed the patients. Another limitation was the broad age range within the groups.

In conclusion, according to the results of this study, toxoplasmosis appears to play no role in the etiology of autism. An advanced research with a higher numbers of subjects using Western blot as the gold standard method is required in order to obtain more definitive results.

Conflict of Interest: Authors declared no conflict of interest.

Financial Disclosure: Authors declared no financial support.

Acknowledgements: We would like to thank our ASD patients and their families and Professor Suna Taneli for her inspiration and guidance.


1.APA. Diagnostic and statistical manual of mental disorders, fifth edition. American Psychiatry Association, Washington, DC, 2013.

2.Baron-Cohen S, Scott FJ, Allison C, Williams J, Bolton P, Matthews FE, Brayne C. Prevalence of autism-spectrum conditions: UK school-based population study. Br J Psychiatry 2009; 194:500-509. [CrossRef]

3.Lai MC, Lombardo MV, Baron-Cohen S . Autism. Lancet 2014; 383:896-910. [CrossRef]

4.Ashwood P, Wills S, Van de Water J. The immune response in autism: a new frontier for autism research. J Leukoc Biol 2006; 80:1-15. [CrossRef]

5.Montoya JG, Liesenfeld O. Toxoplasmosis. Lancet 2004; 363:1965-1976. [CrossRef]

6.Henriquez SA, Brett R, Alexander J, Pratt J, Roberts CW. Neuropsychiatric disease and Toxoplasma gondii infection. Neuroimmunomodulation 2009; 16:122-133. [CrossRef]

7.Al-Hussainy NH, Al-saedi AM, Al-lehaibi JH, Al-lehaibib YA, Al-Sehli YM, Afifi MA. Serological evidences link toxoplasmosis with schizophrenia and major depression disorder. J Microsc Ultrastruct 2015; 3:148-153. [CrossRef]

8.Alvarado-Esquivel C, Urbina-Alvarez JD, Estrada-Martinez S, Torres-Castorena A, Molotla-de-Leon 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. [CrossRef]

9.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 Ment Dis 2009; 197:905-908. [CrossRef]

10.Emelia O, Amal RN, Ruzanna ZZ, Shahida H, Azzubair Z, Tan KS, Noor Aadila S, Siti NA, Aisah MY. Seroprevalence of anti-Toxoplasma gondii IgG antibody in patients with schizophrenia. Trop Biomed 2012; 29:151-159.

11.Flegr J, Havlicek J, Kodym P, Maly M, Smahel Z. Increased risk of traffic accidents in subjects with latent toxoplasmosis: a retrospevtive case-control study. BMC Infect Dis 2002; 2:11. [CrossRef]

12.Gale SD, Brown BL, Berrett A, Erickson LD, Hedges DW. Association between latent toxoplasmosis and major depression, generalised anxiety disorder and panic disorder in human adults. Folia Parasitol (Praha) 2014; 61:285-292. [CrossRef]

13.Hinze-Selch D, Daubener W, Erdag S, Wilms S. The diagnosis of a personality disorder increases the likelihood for seropositivity to Toxoplasma gondii in psychiatric patients. Folia Parasitol (Praha) 2010; 57:129-135. [CrossRef]

14.Ling VJ, Lester D, Mortensen PB, Langenberg PW, Postolache TT. Toxoplasma gondii seropositivity and suicide rates in women. J Nerv Ment Dis 2011; 199:440-444. [CrossRef]

15.Miman O, Mutlu EA, Ozcan O, Atambay M, Karlidag R, Unal S. Is there any role of Toxoplasma gondii in the etiology of obsessive-compulsive disorder Psychiatry Res 2010; 177:263-265. [CrossRef]

16.Mortensen PB, Norgaard-Pedersen B, Waltoft BL, Sorensen TL, Hougaard D, Torrey EF, Yolken RH. 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. [CrossRef]

17.Tedla Y, Shibre T, Ali O, Tadele G, Woldeamanuel Y, Asrat D, Aseffa A, Mihret W, Abebe M, Alem A, Medhin G, Habte A. Serum antibodies to Toxoplasma gondii and Herpesvidae family viruses in individuals with schizophrenia and bipolar disorder: a case-control study. Ethiop Med J 2011; 49:211-220.

18.Yagmur F, Yazar S, Temel HO, Cavusoglu M. May Toxoplasma gondii increase suicide attempt-preliminary results in Turkish subjects Forensic Sci Int 2010; 199:15-17. [CrossRef]

19.Halonen SK, Weis LM. Toxoplasmosis. Handb Clin Neurol 2013; 114:125-145. [CrossRef]

20.Werner H, Masihi KN, Senk U. Latent toxoplasma-infection as a possible risk factor for CNS-disorders. Zentralbl Bakteriol Mikrobiol Hyg A 1981; 250:368-375.

21.Carter CJ. Toxoplasmosis and polygenic disease susceptibility genes: extensive toxoplasma gondii host/pathogen interactome enrichment in nine psychiatric or neurological disorders. J Pathog 2013; 2013:965046. [CrossRef]

22.Thong YH. Reptilian behavioural patterns in chilhood autism. Med Hypotheses 1984; 13:399-405. [CrossRef]

23.Prandovszky E, Gaskell E, Martin H, Dubey JP, Webster JP, McConkey GA. PLoS One 2011; 6:e23866. [CrossRef]

24.Zhu S. Psychosis may be associated with toxoplasmosis. Med Hypothesis 2009; 73:799-801. [CrossRef]

25.Gillberg C, Svennerholm L. CSF monoamines in autistic syndromes and other pervasive developmental disorders of early childhood. Br J Psychiatry 1987; 151:89-94. [CrossRef]

26.Nakamura K, Sekine Y, Ouchi Y, Tsujii M, Yoshikawa E, Futatsubashi M, Tsuchiya KJ, Sugihara G, Iwata Y, Suzuki K, Matsuzaki H, Suda S, Sugiyama T, Takei N, Mori N. Brain serotonin and dopamine transporter bindings in adults with high-functioning autism. Arch Gen Psychiatry 2010; 67:59-68. [CrossRef]

27.Prandota J. Neuropathological changes and clinical features of autism spectrum disorder participants are similar to that reported in congenital and chronic cerebral toxoplasmosis in humans and mice. Res Autism Spectr Disord 2010; 4:103-118. [CrossRef]

28.Prandota J. Autism spectrum disorders may be due to cerebral toxoplasmosis associated with chronic neuroinflammation causing persistent hypercytokinemia that resulted in an increased lipid peroxidation, oxidative stress, and depressed metabolism of endogenous and exogenous substances. Res Autism Spectr Disord 2010; 4:119-155. [CrossRef]

29.Sucuoglu B, Oktem F, Akkok F, Gokler B. A study about childhood autism scales. Psikiyatri, Psikoloji, Psikofarmakoloji (3P) Dergisi 1996; 4:116-121. (Turkish)

30.Afsharpaiman S, Skandari A, Maryam ZJ, Radfar S, Shirbazoo S, Amirsalari S, Torkaman M. An assessment of Toxoplasmosis antibodies seropositivity in children suffering Autism. Tehran University Medical Journal 2014; 72:106-112.

31.Prandota J, Elleboudy NAF, Ismail KA, Zaki OK, Shehata HH. Increased seroprevalence of chronic toxoplasmosis in autistic children: special reference to the pathophysiology of IFN-gamma and NO overproduction. Int J Neurology Res 2015; 1:102-122. [CrossRef]

32.Jones JL, Kruszon-Moran D, Wilson M, McQuillan G, Navin T, McAuley JB. Toxoplasma gondii infection in the United States: seroprevalence and risk factors. Am J Epidemiol 2001; 154:357-365. [CrossRef]

33.Asci Z, Akgun S. The evaluation of toxoplasma gondii (T.gondii) serology results among cases who admitted to the serology laboratory of a hospital in afyon city. Turkiye Parazitol Derg 2015: 39:9-12. (Turkish) [CrossRef]

34.Boluk S, Ozyurt BC, Girginkardesler N, Kilimcioğlu AA. Evaluation of serological results of patients with suspected Toxoplasmosis admitted to the medical parasitology laboratory of Celal Bayar University Hospital between 2006-2010. Turkiye Parazitol Derg 2012; 36:137-141. (Turkish) [CrossRef]

35.Iraz M, Gultepe B, Ceylan A, Doymaz MZ. Seroprevalence of toxoplasma and rubella in childbearing age women. Abant Medical Journal 2015; 4:11-14. (Turkish) [CrossRef]

36.Okur M. Van Gölü havzasında 0–18 yaş grubu çocuklarda Sitomegalovirus, Rubella ve Toksoplazma seroprevalansı. Konuralp Tip Dergisi 2012; 4:13-16. (Turkish)

37.Baron-Cohen S, Lombardo MV, Auyeung B, Ashwin E, Chakrabarti B, Knickmeyer R. Why are autism spectrum conditions more prevalent in males PLoS Biol 2011; 9:e1001081. [CrossRef]

38.Abdoli A, Dalimi A. Are there any relationships between latent Toxoplasma gondii infection, testosterone elevation, and risk of autism spectrum disorder Front Behav Neurosci 2014; 8:339. [CrossRef]

39.Hodková H, Kolbeková P, Skallová A, Lindová J, Flegr J. Higher perceived dominance in Toxoplasma infected men--a new evidence for role of increased level of testosterone in toxoplasmosis-associated changes in human behavior. Neuro Endocrinol Lett 2007; 28:110-114.

40.Leweke FM, Gerth CW, Koethe D, Klosterkötter 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; 254:4-8. [CrossRef]

41.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. [CrossRef]

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