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Toxoplasma gondii Infection and Aggression in Autistic Children

Hamid, Najmeh PhD*; Azizy, Boshra MSc*; Hamidinejad, Hossein PhD

Author Information
The Pediatric Infectious Disease Journal: June 2022 - Volume 41 - Issue 6 - p 492-495
doi: 10.1097/INF.0000000000003516
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Abstract

Toxoplasma gondii infection is usually caused by ingestion oocytes from soil, water, and food or by ingestion of the tissue cysts through the consumption of raw or undercooked meat and meat products.1 Another important route is transmission of the parasite is through placenta previa, in which 5 of every 1000 female infected with toxoplasmosis during pregnancy transmit the parasite to their fetus.2,3

Assessment of changes in behavior after T. gondii infection can be approached by different types of behavioral tests. Locomotion and anxiety in an open-field arena, fear conditioning, neo phobia towards food and hippocampal learning are for example not influenced by infection, while an aversion to cat odor shifts to attraction. Furthermore, other disorders, such as autism, antisocial personality disorder, obsessive compulsive disorder and Asperger syndrome have been associated with toxoplasmosis.4T. gondii causes cysts in the brain, which can increase dopamine levels and inflammation there. Inflammation affects other parts of the brain, especially regulation of steroid hormones.5 High levels of steroid hormone are associated with low cell immunity. It has been hypothesized that such changes could contribute to the survival of this parasite in the body.6 Especially in immunocompromised patients, activation of T. gondii may cause psychological and neurological symptoms.7T. gondii inflammation in the brain can affect the hypothalamic-pituitary-adrenal axis. Furthermore, observations suggest that decreased serotonergic function of the brain causes behavioral dysfunction, including impulsive aggression, suicide and substance abuse or other mental disorders associated with impulse control.8–10

In some studies,1113 a significant relationship was observed between positive toxoplasma and testosterone. In fact, the increase in testosterone in infected people is due to an increase in dopamine in the brain. Observations suggest that such changes in the serotonergic function of the brain causes behavioral dysfunction, including impulsive aggression, suicide and substance abuse or other mental disorders associated with impulse control.14,15 In this study, we sought to investigate the relationship of aggression in children with T. gondii infection.

OBJECTIVES

The aims of this research were 2-fold: (1) to investigate differences in children with autism and normal children in terms of the rate of infection with T. gondii, the components of aggression and (2) to compare children with autism and normal children in terms of T. gondii infection rates based upon the presence of IgM and IgG antibodies.

METHODS

The research design was an analytical (comparative) cross sectional study. The study population included male preschool students up to the sixth grade in the Dr Hoshyar public elementary school and 3–12-year-old children with autism in the same school. Fifty children with autism were selected as the experimental group and 50 children without autism were selected as the control group. These children were matched in terms of age, socioeconomic status, lack of acute physical and mental illness. After obtaining informed consent, we administered an interview to parents of these children. We identified control students from children without autism or other neurological disorders. Furthermore, the excluding criteria for control group were having obvious signs and symptoms of psychosis, suffering from other mental disorders or chronic diseases, having obvious physical disorder, sensory-motor or developmental-motor disorders, intellectual disability and other criteria considered in this research. Furthermore, the inclusion criteria for parents of children in this study included having a minimum literacy and agreeing to participate in the study.

Data Collection Instrument

Infection

Infection with T. gondii parasite serology was measured using enzyme-linked immunosorbent assay method. Commercially available enzyme-linked immunosorbent assay kits (Trinity Biotech) were used according to the manufacturer’s instructions, and a microliter plate reader was used to determine the IgG and IgM antibodies in the sera. This technique is based on the detection of an antigen or antibody on a solid surface directly or secondary with the help of label antibodies and the creation of products that can be read by a spectrophotometer.

Aggression Inventory

Primary School Aggression Scale

This scale is a 43-item questionnaire with a Likert scale for assessing the physical, communicational, verbal aggression and impulsive anger of preschool children. This questionnaire was first used in 2008 by Vahidi et al16 using the aggression questionnaire of Shahim primary school children and Ahvaz aggression questionnaire to assess the predisposition of various aspects of aggression in children. This questionnaire, completed by the educator or parent of the child, includes a total score of four sub scales: (1) verbal aggression, (2) physical aggression, (3) communicational aggression and (4) impulsive anger. Also, the cutoff point in selecting aggressive people based on this questionnaire is two standard deviations above the average. Cronbach alpha has a validity coefficient of 0.98 on the whole scale and in the 4 factors of verbal-aggressive, physical-aggressive, communicational aggression and impulsive anger, respectively, 0.93, 0.92, 0.94 and 0.88, respectively. Is17 Cronbach alpha ratios were obtained in the overall scale of 0.98 and in the 4 factors of verbal aggression, physical aggression, communicational aggression and impulsive anger, in the order of 0.93, 0.92, 0.94 and 0.88, respectively.18 In the present study, Cronbach alpha validity coefficient for the subscales of verbal aggression, physical aggression, communicational aggression and the total score of the aggression scale was 0.78, 0.83, 0.86 and 0.92, respectively.

Procedure

The study population was divided into two groups (experimental and control) using the available and random sampling method. Furthermore, after obtaining written consent from the children’s parents, files were compiled for each patient, including demographic information, current disease type, autism diagnosis time, characteristics and problems of the child at birth and associated disorders (such as mental retardation, seizures and other disorders). Then, on both days, according to the readiness of the children and their families, 5 mL of blood was taken from each child by an experienced nurse in Ahvaz Health Center No. 5, and at the same time, their parents and some their teachers were asked and they responded to the aggression test. Then, after coding on each blood sample, the samples were transferred to the laboratory of the Faculty of Veterinary Medicine (Department of Parasitology) located in Shahid Chamran University of Ahvaz, and after centrifuging the blood samples and separating the blood serum, they were stored and labeled in the laboratory freezer at -20°C until use. After collecting all 100 serum samples, the samples were examined by enzyme-linked immunosorbent assay sera test to determine the level of anti-IgG (chronic phase) and IgM (acute phase) antibodies against T. gondii by a compare in experimental and control groups. To determine the optical density of existing antibodies, microtiter plate reader was used to determine the level of anti-IgG and anti-IgM to detect the acute and chronic phases of toxoplasmosis respectively. Finally, results were compared in the experimental and control groups.

Data Analysis

The differences between autistic and normal group in T. gondii infection, noninfection and chronic infection were analyzed by χ2. Furthermore, the rate of aggression was analyzed between two groups by Uman Vitny method.

RESULTS

As can be seen in Table 1, a comparison between Autistic and normal children in terms of infection with the T. gondii shows that there was a significant difference between the 2 groups (χ2 = 9, 214, P < 0.001). Autistic children were more likely to be infected with the toxoplasma protozoan than the normal group.

TABLE 1. - Comparison of Autistic and Normal Children in Terms of Infection With T. gondii
Toxoplasma Infection Group Test Results
Normal Autism
Number Percent Number Percent
Noninfection 45 0.90 33 0.66 χ2 = 9.214
df = 2
P < 0.001
Acute infection 1 0.2 8 0.16
Chronic infection 4 0.8 9 0.18

As can be seen in Table 2, the amount of non-parametric statistics of U Mann-Whitney in the component of aggression in Autistic and normal children showed a significant difference, and these differences indicated that the average components of aggression in children with autism are higher than those of normal children.

TABLE 2. - Comparison the Mean of Aggression in Autistic and Normal Children
Variables Group Mean Rating Uman Vitny Z P value
Physical aggression Normal 42.30 840.000 −2.83 0.001
Autism 58.70
Verbal aggression Normal 39.25 687.50 −3.88 0.001
Autism 61.75
Communicational aggression Normal 41.24 787.00 −3.20 0.002
Autism 59.76
Impulsive anger Normal 41.60 805.00 −3.16 0.00
Autism 59.40

As can be seen in Table 3, the results of the Kruskal-Wallis test showed that there was a significant difference in all components of aggression in the three groups of noninfected, acute and chronic infection with T. gondii parasite in children with autism (P ˂ 0.001).

TABLE 3. - Results of the Kruskal-Wallis Test to Compare the Components of Aggression in 3 Groups
Variables Groups Number Mean Rating χ2 df P value
Physical aggression Uninfected 33 20.71 11.20 2 0.001
Acute infection 8 37.94
Chronic infection 9 32
Verbal aggression Uninfected 33 19.02 19.33 2 0.001
Acute infection 8 39.13
Chronic infection 9 37.17
Communicational aggression Uninfected 33 19.15 18.53 2 0.001
Acute infection 8 38.37
Chronic infection 9 37.23
Impulsive anger Uninfected 33 18.56 23.56 2 0.001

DISCUSSION

In this study, a comparison between autistic and normal children in terms of T. gondii infection showed that there was a significant difference between the 2 groups with autistic children having a higher rate of infection with T. gondii than the control group. These results are consistent with previous research.19 In previous studies by Rajabpour et al,20 Bransfield,21 Gillberg and Coleman,22 Aly et al,23 Patterson et al24 and Prandota,25 there is a significant relationship between maternal infection in the first months of pregnancy and its effect on the fetal central nervous system, abortion and autistic behaviors in their infants.

These differences in outcomes appear to have been partly due to differences in the selection of control groups in various T. gondii studies. Another result of this study was a significant difference between the infected group and the control group in terms of aggression. The results showed that the autism group was more aggressive than the control group.

The results also showed that the children with autism who were infected with the Toxoplasma parasite were more aggressive than noninfected children in all components of aggression. However, there was no significant difference between serologic evidence of acute versus chronic infection, and the rate of aggression revealing just chronic infection was correlated with autism and aggression. However, much research has been done on the infection with this parasite and its effect on aggression, as the results of AL-Maamuri et al,26 Al-hassnawi,27 Zhao and Ewald28 and Flegr and Hrdý29 studies are related to the infection with T. gondii and its effect on aggression concur with the results of the present study. In addition previous studies of AL-Hadad et al,13 Flegr et al,30 and Flegr and Hrdý29 have found a significant association between infection with this parasite and disruption of dopamine and testosterone secretion. As one of the major neurotransmitters in the brain, serotonin plays a significant role in the development of aggression.31

In summary, the results showed that the autistic children who infected with T. gondii in comparison with non-infected children in the same group at all components of aggression were more aggressive, it can be said that although our hypothesis was confirmed in that a significant relationship was found between T. gondii infection and adverse behavioral outcomes. However, as the sample size was small, our results should be validated in other settings. It seems that more studies are needed in this field in the future.

ACKNOWLEDGMENTS

This study was supported by Shahid Chamran University for project number 321, and the authors wish to thank the Research center of Shahid Chamran University. Furthermore, the authors to thank the parasitology laboratory of the Faculty of Veterinary Medicine for performing the enzyme immunoassay tests for T. gondii antibodies in these samples, the General Department of Welfare of Ahvaz and other persons who helped us in this research.

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    Keywords:

    Toxoplasma gondii; aggression; autism; normal children

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