TOXOPLASMOSIS AMONG SCHIZOPHRENIC PATIENTS

Document Type : Original Article

Authors

1 Parasitology Department, Al-Azhar Faculty of Medicine

2 Psychiatry Department, Al-Azhar Faculty of Medicine

Abstract

Background: A variety of neurologic symptoms, including in-coordination, tremors, head-shaking, and seizures, have been described in sheep, pigs, cattle, rabbits, and monkeys infected with T. gondii. Up to a third of the world's human population is estimated to carry a Toxoplasma infection.
Objective: Studying the possible association between Toxoplasma gondii infection and schizophrenia by using ELISA technique for detection of Toxoplasma IgG and IgM.
Subjects and Methods: The study was carried out at Psychiatry Department, Al-Azhar University Hospital (New-Damietta) from July 2014 to January 2015. The study included 100 schizophrenic patients. Another hundred normal persons of the same age and sex, without psychosis or symptoms and signs suggesting toxoplasmosis were selected as a control group. All persons were subjected to detailed history taking, laying stress on risk factors of toxoplasmosis (such as contact with cats, eating undercooked meat and contact with the soil) and manifestations of schizophrenia. The separated serum was stored frozen at (-20°C) until used for estimation of Toxoplasma Specific IgG and IgM titers.
Results: The prevalence of toxoplasma infection detected either by IgM or IgG was significantly higher in schizophrenic patients (28.0%, 58.0% respectively). Patients with toxoplasmosis were significantly younger, and incidence decreased with increased age. Risk factors and family history of schizophrenia were significantly higher in study group. Considering positive cases, those factors and family history were not significantly increased. Even eating undercooked meat and family history of schizophrenia were significantly lower.
Conclusion: Results of the present study shed light on the prevalence of toxoplasmosis in schizophrenic patients and revealed that toxoplasmosis was significantly higher in those patients when compared to control group. Thus, schizophrenia may be linked to this infection. However, a future large scale randomized studies were needed to confirm this association.  

Keywords


TOXOPLASMOSIS AMONG SCHIZOPHRENIC PATIENTS

 

By

 

Ahmed Mohamed Sayed Baioumy, Mohamed Metwally Abo Alabbas* and Mohamed Noshy Anis El-Sherbiny El-Baz

 

Parasitology and Psychiatry* Departments; Al-Azhar Faculty of Medicine

 

ABSTRACT

Background: A variety of neurologic symptoms, including in-coordination, tremors, head-shaking, and seizures, have been described in sheep, pigs, cattle, rabbits, and monkeys infected with T. gondii. Up to a third of the world's human population is estimated to carry a Toxoplasma infection.

Objective: Studying the possible association between Toxoplasma gondii infection and schizophrenia by using ELISA technique for detection of Toxoplasma IgG and IgM.

Subjects and Methods: The study was carried out at Psychiatry Department, Al-Azhar University Hospital (New-Damietta) from July 2014 to January 2015. The study included 100 schizophrenic patients. Another hundred normal persons of the same age and sex, without psychosis or symptoms and signs suggesting toxoplasmosis were selected as a control group. All persons were subjected to detailed history taking, laying stress on risk factors of toxoplasmosis (such as contact with cats, eating undercooked meat and contact with the soil) and manifestations of schizophrenia. The separated serum was stored frozen at (-20°C) until used for estimation of Toxoplasma Specific IgG and IgM titers.

Results: The prevalence of toxoplasma infection detected either by IgM or IgG was significantly higher in schizophrenic patients (28.0%, 58.0% respectively). Patients with toxoplasmosis were significantly younger, and incidence decreased with increased age. Risk factors and family history of schizophrenia were significantly higher in study group. Considering positive cases, those factors and family history were not significantly increased. Even eating undercooked meat and family history of schizophrenia were significantly lower.

Conclusion: Results of the present study shed light on the prevalence of toxoplasmosis in schizophrenic patients and revealed that toxoplasmosis was significantly higher in those patients when compared to control group. Thus, schizophrenia may be linked to this infection. However, a future large scale randomized studies were needed to confirm this association.  

Keywords: Toxoplasma gondii; schizophrenia

  

 

INTRODUCTION

      Toxoplasmosis is a parasitic disease caused by protozoan Toxoplasma gondii (Ryan and Ray, 2004). The parasite infects most genera of warm-blooded animals, including humans, but primary host is the felid (cat) family. Infection occurs by eating infected meat, or ingesting water, soil, or food that has come into contact with infected animal's fecal matter. Transmission can occur from infected mother to fetus during pregnancy. This is why physicians recommended that pregnant woman do not clean litter boxes or eats under-cooked meat products (Dubey, 2005). About one third of world's human population is estimated to carry a Toxoplasma infection (Montoya and Liesenfeld, 2004). 

      The parasite can cause encephalitis and neurological diseases, and can affect the heart, liver, inner ears, and eye (Bin Dajem and Almushait, 2012). Research has also linked toxoplasmosis with attention deficit hyperactivity disorder (ADHD), obsessive compulsive disorder (OCD), and schizophrenia. Numerous studies found a positive correlation between latent toxoplasmosis and suicidal behavior in humans (Ling et al., 2011; Pedersen et al., 2012; Zhang et al., 2012 and Coccaro et al., 2016). Research related to the effects of toxoplasmosis on personality and mental health was awarded the 2014 Nobel Prize in Public Health (Cook et al., 2015).

      The aim of this work was to study the possible association between Toxoplasma gondii infection and schizophrenia by using ELISA technique for detection of Toxoplasma IgG and IgM.

MATERIALS AND METHODS

     The study was carried out at Psychiatry Department, Al-Azhar University Hospital (New-Damietta) from July 2014 to January 2015. The study included 100 patients with symptoms and signs of schizophrenia and fulfilling the inclusion criteria that included hallucinations, voices that converse with or about the patient, disorganized speech and behavior, agitation and delusions. Negative symptoms included poverty of speech, flattened affect, loss of sense of pleasure, lack of will or drive, and social withdrawal. A hundred normal persons of the same age and sex, without schizo-phrenia or symptoms and signs suggesting toxoplasmosis were selected as a control group. The study protocol was explained for all included subjects and an informed consent for participation in the study was obtained. All the studied persons were subjected to detailed history taking, laying stress on risk factors of toxoplasmosis such as contact with felids, eating undercooked meat and contact with the soil and manifestations of schizophrenia. Blood sample was withdrawn aseptically via venipuncture. The separated serum was stored frozen at -20°C until used for estimation of Toxoplasma specific IgG and IgM titers. 

Statistical analysis: The collected data were tabulated and statistically analyzed using statistical package for social science (SPSS) version 16.0 (SPSS Inc. USA); running on IBM compatible personal computer. Qualitative (categorical) data were represented as relative frequency (n) and percent (%) distribution. For comparison between groups, Chi square (X2) test was used. Quantitative data were represented as arithmetic mean and standard deviation (SD). For comparison between two groups, the student t-test was used. For interpretation of results, p value ≤ 0.05 was considered significant.

RESULTS

      In the present work, both study and control groups were comparable as regarding sex, age and residence. There was male predominance in the study group (60.0%). The mean age in study group was 34.25 compared to 35.20 in control group. In addition, there was rural area predominance in study group (71.0% were of rural area). On the other hand, there was significant increase of risk factors (contact with cats, eating undercooked meat and contract with soil) in study group when compared to control group (56.0%, 14%, 39% vs 0.0%, 0.0%, 0.0% respectively). In addition, there was significant increase of family history of schizophrenia in study group when compared to control group (28.0% vs 0.0% respectively). Positive IgG for toxoplasma significantly increased in study group (58.0%) vs (13.0%) in control group. Similarly, there was a significant increase of positive IgM for toxoplasma in study group when compared to control group (28.0% vs 4.0% respectively-Table 1).

     In cases with positive IgM, positive cases were mostly males, but the difference was statistically non-significant.  Positive cases significantly increased in third decade (53.6%) when compared to fourth, fifth or sixth decades (35.7%, 7.1% and 3.6% respectively). In addition, positive IgM cases were signifi-cantly related to rural area (67.9%). Contact with cats increased, but the difference was non-significant; while, eating undercooked meat was significantly lower in positive IgM cases (14.3%), and contact with soil was distributed equally. Family history of schizophrenia was not significantly different. Looking at distribution of different variables in cases positive for IgG, positive cases were significantly in younger age, and incidence decreased with increasing age. Also, rural area significantly increased, and both eating undercooked meats and family history of schizophrenia were significantly lower (Table 2).

 

 

Table (1): Comparison between control and study groups as regards to studied variables.

Variables

Control group

Study group

Test

P value

Sex (No.%)

Males

59(59.0%)

60(60.0%)

0.02

0.88

Females

41(41.0%)

40(40.0%)

Age (years)

35.20±10.31

34.25±9.51

0.67

0.49

Residence

Rural

70 (70.0%)

71(71.0%)

0.01

0.99

Urban

30(30.0%)

29(29.0%)

 

Risk

 factors

Contact with cats

0(0.0%)

56(56.0%)

200.0

<0.001

Eating undercooked meat

0(0.0%)

14(14.0%)

Contact with soil

0(0.0%)

39(39.0%)

Family history of schizophrenia

0(0.0%)

28 (28.0%)

32.55

<0.001

Positive IgG for toxoplasma

13(13.0%)

58(58.0%)

44.21

<0.001

Positive IgM for toxoplasma

4(4.0%)

28(28.0%)

21.41

<0.001

 

Table (2): Distribution of studied variables positive for IgM and IgG in study group

Variables

Positive IgM

(no=28)

P value

Positive IgG

(no=58)

P value

Sex

Males

17(60.7%)

0.25

 

36(62.1%)

0.06

 

Females

11(39.3%)

22(37.9%)

Age

(years)

Third decade

15(53.6%)

 

 

<0.001

27(46.6%)

 

 

0.001

Fourth decade

10(35.7%)

18(31.0%)

Fifth decade

2(7.1%)

11(19.0%)

Sixth decade

1(3.6%)

2(3.4%)

Residence

Rural

19(67.9%)

0.05

42(72.4%)

0.001

Urban

9(32.1%)

16(27.6%)

Contact with

cats

Yes

15(53.6%)

0.71

 

32(55.2%)

0.43

 

No

13(46.4%)

26(44.8%)

Eat undercooked

meat

Yes

4(14.3%)

<0.001

7(12.1%)

<0.001

No

24(85.7%)

51(87.9%)

Contact with

Soil

Yes

14(50.0%)

1.0

 

23(39.7%)

0.12

 

No

14(50.0%)

35(60.3%)

Family history of

Schizophrenia

Positive

13(46.4%)

0.71

 

12(20.7%)

<0.001

Negative

15(53.6%)

46(79.3%)



DISCUSSION

      In many studies conducted in different parts in the world, the percentage of seropositive schizophrenic cases for Toxoplsmosis. IgG and IgM were higher than other apparently healthy persons. They were 40%, 53% and 67.7% positive cases for Toxoplasma IgG in the studies conducted by Tamer et al. (2008) in Turkey, Sabah and Mahfoth, (2009) in Iraq and Alipour et al. (2011) in Iran respectively, while there were 5% and 16% positive for Toxoplasma IgM in the studies conducted by Tamer et al, (2008) in Turkey and Fadheelah et al. (2011) in Iraq.

     The previous data and findings drew our attention to the aim of the present study which was the significance and importance to study prevalence of toxoplasmosis among schizophrenic patients. The resulting data revealed that there was statistically non-significant difference between cases and control group regarding sex, age and residence. The consumption of undercooked meat was found to be associated with an increased and significant incidence of toxoplasmosis among the study group. Regarding family history of schizophrenia, there was a statistically significant increase in positive cases among the study group in comparison to no positive family history among the control group. History of cat contact was highly significant among IgG positive cases and among IgM positive cases in comparison to control group. Third decade was the most common age in both cases and controls (45.0% of cases and 42.0% of controls were in the third decade). There was no statistical significance difference of age in cases when compared to controls. The obtained results coincided with that obtained by Alipour et al. (2011) and Khademvatan et al. (2014).

     As regard age and seropositivity, we found that positive IgM cases were in third decade, 35.7% in fourth decade, 7.1% in fifth decade and 3.6% in sixth decade. The positive IgG cases were 46.6% in third decade, 31.0% in fourth decade, 19.0% in fifth decade and 3.4% in sixth decade. Both IgM and IgG were statistically significant in third and fourth decades of age. The obtained results coincided with that obtained by Sabah and Mahfoth (2009)

      In the present study, there were 58% with positive IgG and 42% with negative IgG in the patient group, while in the control group there were 13.0% IgG positive and 87.0% IgG negative and there was statistically significant increase in positive cases in the study group in comparison to control group. These results were slightly higher than that obtained by Tamer et al. (2008) who found that IgG seropositivity was 40%, which may be attributed to the geographical distribution of studied cases and controls, sensitivity and specificity of the used materials. However, the obtained results coincided with that obtained by Sabah and Mahfoth (2009) in Iraq and Alipour et al., (2011) in Iran.

     Regarding toxoplasmosis IgM, there were statistically significant increases in positive cases among the study group in comparison to the control group. These results are close to those obtained by Fadheelah et al. (2011) in Iraq.

     As regard sex, the majority of positive IgG and IgM cases were males, but the difference was statistically insignificant. As regard residence, both IgG and IgM were statistically significant higher in rural areas than urban areas. The obtained results coincided with that obtained by Sabah & Mahfoth (2009), and Elsheikha et al. (2016).

     The findings and results of the present study should alert physicians and psychiatrists that toxoplasmosis should be suspected in patients presenting with schizophrenia.

REFERENCES

1. Alipour A, Shojaee S, Mohebali M, Tehranidoost M, Abdi –Masoleh F and Keshavaraz H. (2011):  Toxoplasma infec-tion in schizophrenia patients, a comparative study with control group. Iranian J. Parasitol., 6(2): 31-37.

2. Bin Dajem SM and Almushait MA. (2012): Detection of Toxoplasma gondii DNA by PCR in blood samples collected from pregnant Saudi women from the Asser region, Saudi Arabia.Annals of Saudi Med.,32 (5): 507–12.

3. Coccaro EF, Lee R, Groer MW, Can A, Coussons-Read M and Postolache TT. (2016): Toxoplasma gondii infection: relationship with aggression in psychiatric subjects. J Clin Psychiatry., 77(3):334-41.

4. Cook TB, Brenner LA, Cloninger CR, Langenberg P, Igbide A, Giegling I, Hartmann AM, Konte B and Friedl M. (2015): Latent infection with Toxoplasma gondii: association with trait aggression and impulsivity in healthy adults. J Psychiatr Res., 60:87-94.

5. Dubey JP. (2005): Toxoplasmosis In: Topley and Wilson in Microbiology and Microbial infections. Parasitology, 10th edition, Pbl. ASM Press, USA, pp 115-119.

6. Elsheikha HM, Büsselberg D and Zhu XQ. (2016): The known and missing links between Toxoplasma gondii and schizophrenia. Metab Brain Dis., 2016 Apr 4. [Epub ahead of print]

7. Fadheelah SJ, Fekri NY, Mohammed AH and Mohamed DJ. (2011): Toxoplasmosis among schizophrenic patients in Al-Rashad teaching hospital, Al-Qadisiah Med J., 7:23-32.

8. Khademvatan S, Saki J, Khajeddin N, Izadi-Mazidi M, Beladi R, Shafiee B and Salehi Z. (2014): Toxoplasma gondii Exposure and the Risk of Schizophrenia. Jundishapur J Microbiol., 7(11): e12776-e12777.

9. Ling VJ, Lester D, Mortensen PB, Langenberg PW and Postolache TT. (2011): Toxoplasma gondii Seropositivity and Suicide rates in Women". The Journal of Nervous and Mental Disease, 199 (7): 440–444.

10. Montoya JG and Liesenfeld O. (2004): Toxoplasmosis. Lancet, 363 (9425): 1965–76.

11. Pedersen MG, Mortensen PB, Norgaard-Pedersen B and Postolache TT. (2012): Toxoplasma gondii infection and self-directed violence in mothers. Arch General Psychiatr., 69 (11): 1123–30.

12. Ryan KJ and Ray CG. (2004):  Sherris Medical Microbiology (4th Ed.). Pbl. McGraw Hill, USA.pp. 723–7.

13. Sabah SM and Mahfouth SH. (2009): Seroprevalence of toxoplasmosis among schizophrenic patients. Yemen J Med Sci., 1(3): 1-7.

14. Tamer GS, Dundar D, Yalug I, Caliskan S, Yazar S and Aker A. (2008): The schizophrenia and Toxoplasma gondii connection: infectious, immune or both? PubMed., 25 (7): 703-9.

15. Zhang Y, Träskman-Bendz L, Janelidze S, Langenberg P, Saleh A and Constantine N. (2012): Toxoplasma gondii immunoglobulin G antibodies and nonfatal suicidal self-directed violence. J Clin Psychiatry., 73 (8): 1069–76.

 


التوکسوبلازمـا لـدی مرضــــــی الفصــــــام

 

أحمد محمد سید بیومی - محمد متولی أبوالعباس* - محمد نصحی أنیس الشربینی

 

قسم الطفیلیات الطبیة وقسم الأمراض النفسیة * - کلیة طب الأزهر

 

خلفیة البحث: فی الحیوانات (مثل الأغنام، الخنازیر، الماشیة، الأرانب والقرود)  التی أصیبت بالتوکسوبلازما وجد أن هناک مجموعة من الأعراض العصبیة المختلفة مثل عدم الإتزان، والرعشة، وهز الرأس، والتشنجات. وقد وجد أن حوالی ثلث سکان العالم الثالث یحملون طفیل التوکسوبلازما.

الهدف من البحث: صممت الدراسة الحالیة بهدف تقییم الإرتباط المحتمل بین العدوی بالتوکسوبلازما وبین إضطراب الفصام بإستخدام تقنیة الإلیزا لإکتشاف الأجسام المضادة من النوع (جی) و (إم) (العدوی الحادة والمزمنة). 

المرضی وطرق البحث: أجریت الدراسة الحالیة بقسم الطب النفسی (مستشفی طب الأزهر بدمیاط - جامعة الأزهر). فی الفترة من یولیو 2014 إلی ینایر 2015. وقد اشتملت الدراسة 100 مریض من مرضی الفصام. کما تم تضمین 100 شخص من الأصحاء من نفس المجموعة العمریة والنوع کمجموعة ضابطة. وقد تم أخذ التاریخ المرضی بصورة مفصلة، مع الترکیز علی عوامل الخطورة بالنسبة للإصابة بالتوکسوبلازما، مثل الاحتکاک بالقطط، وأکل لحم غیر مطهو بصورة کاملة، والاحتکاک بالتربة)، بجانب أعراض الفصام.  وقد تم استخلاص المصل من عینات الدم، عند درجة حرارة -20 درجة مئویة، حتی وقت قیاس الأجسام المضادة للتوکسوبلازما. ولم یتم إضافة أی مادة حافظة لعینة المصل لتجنب تثبیط تفاعلات الإنزیمات.

النتائج:  معدل إنتشار عدوی التوکسوبلازما سواء الإصابة الحادة أو المزمنة کان أعلی بصورة یعتد بها من الناحیة الإحصائیة لدی مرضی الفصام مقارنة بالمجموعة الضابطة. وبالنسبة للمرضی المصابین بالتوکسوبلازما کانوا أصغر فی العمر بدرجة یعتد بها إحصائیا، ووجد أن معدل الإصابة بالتوکسوبلازما یقل مع تقدم العمر. ووجد أن عوامل الخطورة للإصابة والتاریخ العائلی الموجب، للتوکسوبلازما کانت أکثر لدی مجموعة الدراسة مقارنة بالمجموعة الضابطة.

الاستنتاج: ألقت نتائج الدراسة الضوء علی معدل الإصابة بالتوکسوبلازما لدی مرضی الفصام، ووجد أن معدل الإصابة أکثر بدرجة یعتد بها إحصائیا لدی هؤلاء المرضی مقارنة بالمجموعة الضابطة. ولذلک فثمة إرتباط بین إضطراب إلفصام والإصابة بالتوکسوبلازما، ولذلک یوصی بدراسات مستقبلیة علی نطاق واسع لتأکید أو نفی تلک العلاقة.  

REFERENCES
1. Alipour A, Shojaee S, Mohebali M, Tehranidoost M, Abdi –Masoleh F and Keshavaraz H. (2011):  Toxoplasma infec-tion in schizophrenia patients, a comparative study with control group. Iranian J. Parasitol., 6(2): 31-37.
2. Bin Dajem SM and Almushait MA. (2012): Detection of Toxoplasma gondii DNA by PCR in blood samples collected from pregnant Saudi women from the Asser region, Saudi Arabia.Annals of Saudi Med.,32 (5): 507–12.
3. Coccaro EF, Lee R, Groer MW, Can A, Coussons-Read M and Postolache TT. (2016): Toxoplasma gondii infection: relationship with aggression in psychiatric subjects. J Clin Psychiatry., 77(3):334-41.
4. Cook TB, Brenner LA, Cloninger CR, Langenberg P, Igbide A, Giegling I, Hartmann AM, Konte B and Friedl M. (2015): Latent infection with Toxoplasma gondii: association with trait aggression and impulsivity in healthy adults. J Psychiatr Res., 60:87-94.
5. Dubey JP. (2005): Toxoplasmosis In: Topley and Wilson in Microbiology and Microbial infections. Parasitology, 10th edition, Pbl. ASM Press, USA, pp 115-119.
6. Elsheikha HM, Büsselberg D and Zhu XQ. (2016): The known and missing links between Toxoplasma gondii and schizophrenia. Metab Brain Dis., 2016 Apr 4. [Epub ahead of print]
7. Fadheelah SJ, Fekri NY, Mohammed AH and Mohamed DJ. (2011): Toxoplasmosis among schizophrenic patients in Al-Rashad teaching hospital, Al-Qadisiah Med J., 7:23-32.
8. Khademvatan S, Saki J, Khajeddin N, Izadi-Mazidi M, Beladi R, Shafiee B and Salehi Z. (2014): Toxoplasma gondii Exposure and the Risk of Schizophrenia. Jundishapur J Microbiol., 7(11): e12776-e12777.
9. Ling VJ, Lester D, Mortensen PB, Langenberg PW and Postolache TT. (2011): Toxoplasma gondii Seropositivity and Suicide rates in Women". The Journal of Nervous and Mental Disease, 199 (7): 440–444.
10. Montoya JG and Liesenfeld O. (2004): Toxoplasmosis. Lancet, 363 (9425): 1965–76.
11. Pedersen MG, Mortensen PB, Norgaard-Pedersen B and Postolache TT. (2012): Toxoplasma gondii infection and self-directed violence in mothers. Arch General Psychiatr., 69 (11): 1123–30.
12. Ryan KJ and Ray CG. (2004):  Sherris Medical Microbiology (4th Ed.). Pbl. McGraw Hill, USA.pp. 723–7.
13. Sabah SM and Mahfouth SH. (2009): Seroprevalence of toxoplasmosis among schizophrenic patients. Yemen J Med Sci., 1(3): 1-7.

14. Tamer GS, Dundar D, Yalug I, Caliskan S, Yazar S and Aker A. (2008): The schizophrenia and Toxoplasma gondii connection: infectious, immune or both? PubMed., 25 (7): 703-9.

15. Zhang Y, Träskman-Bendz L, Janelidze S, Langenberg P, Saleh A and Constantine N. (2012): Toxoplasma gondii immunoglobulin G antibodies and nonfatal suicidal self-directed violence. J Clin Psychiatry., 73 (8): 1069–76.