Toxoplasmosis, but not borreliosis, is associated with psychiatric disorders and symptoms
Schizophrenia Research 2018; 197: 603-604
Toxoplasma antibody titers in mania: A cross sectional study
Mangot, A. G., Shivakumar, V., Saini, V., Subbanna, M., Kalmady, S. V., Venkatasubramanian, G.
Journal of Krishna Institute of Medical Sciences University 2018; 7: 13-20
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Background: Recent studies have found a role of infectious agents, especially Toxoplasma gondii, in pathology of bipolar disorder - mania. Aim and Objectives: This study was conducted with the aim to find the prevalence of toxoplasma antibody titers in Indian patients with mania and to assess its specificity towards the clinical profile. Material and Methods: Thirty-four patients having mania were recruited who were psychotropic naive/free, along with 74 healthy controls. Psychopathology was assessed using structured assessment scales. Serum concentration of Toxoplasma IgG was measured using Diesse Enzywell Toxoplasma IgG immunoassay kit. Results: Mann-Whitney U test revealed that the toxoplasma antibody levels were significantly higher in the mania group than healthy controls (U = 766.5, z = 3.25, p = 0.001). Spearman correlation analyses did not reveal any significant correlation between toxoplasma antibody levels and age at onset (n = 0.19, p = 0.26) or YMRS scores (n = 0.15, p = 0.39). Discussion: The herein reported association could have potential implications in better understanding the pathophysiology of mania and its treatment. This is the first study to evaluate the association between toxoplasma titers and mania in India with only a few studies done elsewhere in the world.
Immunoglobulin sub-class distribution in bipolar disorder and schizophrenia: potential relationship with latent Toxoplasma Gondii infection
Bengoufa, H. D., Godin, O., Doukhan, R., Guen, E. L.,Daban-Huard, C. , Bennabi, M., Delavest, M., Lepine, J. P., Boukouaci, W., Laouamri,H., Houenou, J., Jamain, S., Richard, J. R. , Lecorvosier, P. , Yolken, R., Rajagopal, K., Leboyer, M., Tamouza, R.
Bmc Psychiatry 2018; 18
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Background: Immune dysfunction could play a significant role in the pathogenesis of bipolar disorder (BD) and schizophrenia (SZ), conditions with an underlying pro-inflammatory state. Studies on humoral immune responses (which reflects antibody mediated fight against pathogens) in schizophrenia and bipolar disorder are sparse and often providing contradictory results. The aim of this study was to assess humoral immunity in a group of stable bipolar disorder and schizophrenia patients compared to controls by determining total Immunoglobulins and IgG subclasses and to assess their association with latent Toxoplasma gondii and/or CMV infection. Methods: 334 subjects (124 BD, 75 SZ and 135 Healthy Controls [HC]) were included and tested for humoral immunity by determining the total immunoglobulins (IgG,A and M) and IgG subclasses (IgG1, IgG2, IgG3, IgG4) and their relationship with latent Toxoplasma gondii infection, an established risk factor for BD and SZ. Results: Although lower levels of IgG, IgG1, IgG2, IgG4 and IgA were found among BD as compared to HC and/or SZ, after adjustment for confounding variables, only low levels of IgG and IgG1 in BD remai- ned significant. Strikingly highest levels of antibodies to T. gondii (but not CMV) infection in BD and SZ were associated with lowest levels of IgG3 and IgG4 levels as compared to controls. Conclusions: Schizophrenia and bipolar disorder patients with latent T. gondii specific infection may be more vulnerable to changes in immuno-inflammatory processes than controls with similar latent infectious state. Simultaneous sequential immunological monitoring both in steady state and active disease phases in the same BD and SZ patients are warranted to understand the role of Toxoplasma gondii latency in these disorders.
The relationship between Toxoplasma gondii IgG antibodies and generalized anxiety disorder and obsessive-compulsive disorder in children and adolescents: a new approach
Akaltun, I., Kara, S.S., Kara, T.
Nordic Journal of Psychiatry 2018; 72: 57-62
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Aim:Toxoplasma gondii may play a role in the development of psychiatric diseases by affecting the brain. The purpose of this study was to examine the relation between serum toxoplasma IgG positivity and obsessive-compulsive disorder (OCD) and generalized anxiety disorder (GAD) in children and adolescents.Method: Sixty patients diagnosed with OCD and 60 patients with GAD presenting to the pediatric psychiatry clinic, together with 60 control group subjects with no psychiatric diagnosis, were included in the study. The patients were administered the State-Trait Anxiety Inventory for Children and the Children's Yale-Brown Obsessive Compulsive Scale. Serum toxoplasma IgG levels were determined from blood specimens collected from the study and control groups. The results were then compared using statistical methods.Results: State and trait anxiety levels were significantly higher in the OCD and GAD patients than in the control group (p=.0001/.0001). Serum toxoplasma IgG levels were positive in 21 (35%) of the OCD patients, 19 (31.7%) of the GAD patients and 6 (10%) of the control group. A significant relation was determined between IgG positivity and GAD (p=.003). IgG-positive individuals were determined to have a 4.171-fold greater risk of GAD compared to those without positivity (4.171[1.529-11.378]) (p=.005). A significant relation was also determined between IgG positivity and OCD (p=.001). IgG-positive individuals were determined to have a 4.846-fold greater risk of OCD compared to those without positivity (4.846[1.789-13.126]) (p=.002).Conclusion: This study shows that serum toxoplasma IgG positivity indicating previous toxoplasma infection increased the risk of GAD 4.171-fold and the risk of OCD 4.846-fold in children and adolescents. Further studies are now needed to investigate the relation between T. gondii infection and GAD/OCD and to determine the pathophysiology involved.
The association between suicide attempts and Toxoplasma gondii infection
Bak, J. Shim, S.H., Kwon, Y.J., Lee, H.Y., Kim, J.S., Yoon, H., Lee, Y.J.
Clinical Psychopharmacology Neuroscience 2018; 16: 95-102
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Objective: Chronic 'latent' infection by Toxoplasma gondii is common and most of the hosts have minimal symptoms or they are even asymptomatic. However, there are possible mechanisms by which T. gondii may affect human behavior and it may also cause humans to attempt suicide. This article aimed to investigate the potential pathophysiological relationship between suicide attempts and T. gondii infection in Korea.
Methods: One hundred fifty-five psychiatric patients with a history of suicide attempt and 135 healthy control individuals were examined with enzyme-linked immunoassays and fluorescent antibody technique for T. gondii seropositivity and antibody titers. The group of suicide attempters was interviewed regarding the history of suicide attempt during lifetime and evaluated using 17-item Korean version of Hamilton Depression Scale (HAMD), Columbia Suicide Severity Rating Scale (C-SSRS), State-Trait Anxiety Inventory (STAI) and Korean-Barratt Impulsiveness Scale (BIS).
Results: Immunoglobulin G antibodies were found in 21 of the 155 suicide attempters and in 8 of the 135 controls (p=0.011). The Toxoplasma-seropositive suicide attempters had a higher HAMD score on the depressed mood and feeling of guilt subscales and a higher total score than the seronegative suicide attempters. T. gondii seropositive status was associated with higher C-SSRS in the severity and lethality subscales. T. gondii IgG seropositivity was significantly associated with higher STAI-X1 scores in the suicide attempters group.
Conclusion: Suicide attempters showed higher seroprevalence of T. gondii than healthy controls. Among the suicide attempters, the T. gondii seropositive and seronegative groups showed several differences in the aspects of suicide. These results suggested a significant association between T. gondii infection and psychiatric problems in suicidality.
Clinical and serological predictors of suicide in schizophrenia and major mood disorders
Dickerson, F., Origoni, A., Schweinfurth, L.A.B., Stallings, C., Savage, C.L.G., Sweeney, K., Katsafanas, E., Wilcox, H.C., Khushalani, S., Yolken, R.
Journal of Nervous and Mental Disease 2018; 206: 173-178
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Persons with serious mental illness are at high risk for suicide, but this outcome is difficult to predict. Serological markers may help to identify suicide risk. We prospectively assessed 733 persons with a schizophrenia spectrum disorder, 483 with bipolar disorder, and 76 with major depressive disorder for an average of 8.15 years. The initial evaluation consisted of clinical and demographic data as well as a blood samples from which immunoglobulin G antibodies to herpes viruses and Toxoplasma gondii were measured. Suicide was determined using data from the National Death Index. Cox proportional hazard regression models examined the role of baseline variables on suicide outcomes. Suicide was associated with male sex, divorced/separated status, Caucasian race, and elevated levels of antibodies to Cytomegalovirus (CMV). Increasing levels of CMV antibodies were associated with increasing hazard ratios for suicide. The identification of serological variables associated with suicide might provide more personalized methods for suicide prevention.
Are infectious agents involved in the pathogenesis of postpartum psychosis?
de Witte, L.D., Snijders, G., Litjens, M., Kamperman, A.M., Kushner, S.A., Kahn, R.S., Bergink, V.
Journal of Affective Disorders 2018; 229: 141-144
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Background: Since postpartum psychosis has been linked to activation of the immune system, it has been hypothesized that infectious agents may be involved in the pathogenesis of this disorder. We therefore investigated whether exposure to pathogens that can infect the central nervous system is increased in patients with postpartum psychosis.
Methods: We measured the prevalence and titers of immunoglobulin G (IgG) and M (IgM) to herpes simplex virus type 1 (HSV-1) and 2 (HSV-2), Epstein-Barr virus (EBV), cytomegalovirus (CMV) and Toxoplasma Gondii (TG) in a cohort of patients with postpartum psychosis (n = 81) and compared these to matched postpartum controls. Results: We did not find significant differences in seroprevalence or antibody titers for any of these pathogens.
Limitations: Limitations of this study include the indirect measurement of infectious disease and the cross-sectional design.
Conclusion: Our results do not support the hypothesis that exposure to these neurotropic pathogens is involved in postpartum psychosis.
Latent Toxoplasma gondii infection is associated with decreased serum triglyceride to high-density lipoprotein cholesterol ratio in male patients with schizophrenia
Sagud, M. Vlatkovic, S. Strac, D.S. Sviben, M. Zivkovic, M. Vilibic, M. Vuksan-Cusa, B. Mihaljevic-Peles, A. Pivac, N.
Compr. Psychiat. 2018; 82: 115-120
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Previous studies suggested a complex association between Toxoplasma gondii (TG) infection and host lipid metabolism Both TG infection and metabolic disturbances are very common in patients with schizophrenia, but this relationship is not clear.
Methods: In this cross-sectional study, we evaluated the association between TG seropositivity, serum lipid levels, body mass index (BMI) and metabolic syndrome (MetS) in 210 male inpatients with schizophrenia.
Results: In our sample of schizophrenia patients, with the mean age of 43.90 +/- 12.70 years, the rate of TG seropositivity was 52.38% and the prevalence of MetS was 17%. Patients with the TG antibodies had lower serum triglyceride levels and body weight compared to TG seronegative patients, despite having more frequently received antipsychotics (clozapine, olanzapine risperidone and quetiapine), which are well known to induce weight gain and metabolic abnormalities. However, the only significant change in metabolic parameters, observed in TG seropositive patients with schizophrenia, was decreased serum triglyceride to high-density lipoprotein cholesterol (HDL-C) ratio. No associations were observed between TG seropositivity and serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and glucose levels, waist circumference, BMI and the rate of MetS.
Conclusion: This is the first report of the association between TG infection and decreased serum triglyceride to HDL-C ratio in a sample of carefully selected men with chronic schizophrenia.
Toxoplasma gondii: Biological parameters of the connection to schizophrenia
Xiao, J. C. ,Prandovszky, E. , Kannan,G., Pletnikov, M. V. Dickerson, ,F. , Severance , E. G., Yolken, R. H.
Schizophrenia Bulletin 2018; 44: 983-992
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It is increasingly evident that the brain is not truly an immune privileged site and that cells of the central nervous system are sensitive to the inflammation generated when the brain is fighting off infection. Among the many microorganisms that have access to the brain, the apicomplexan protozoan Toxoplasma gondii has been one of the most studied. This parasite has been associated with many neuropsychiatric disorders including schizophrenia. This article provides a comprehensive review of the status of Toxoplasma research in schizophrenia. Areas of interest include (1) the limitations and improvements of immune-based assays to detect these infections in humans, (2) recent discoveries concerning the schizophrenia-Toxoplasma association, (3) findings of Toxoplasma neuropathology in animal models related to schizophrenia pathogenesis, (4) interactions of Toxoplasma with the host genome, (5) gastrointestinal effects of Toxoplasma infections, and (6) therapeutic intervention of Toxoplasma infections.
Chronic Toxoplasma gondii infection induces anti-N-methyl-D-aspartate receptor autoantibodies and associated behavioral changes and neuropathology
Li, Y, Viscidi, R. P., Kannan, G., McFarland,R., Pletnikov, M. V., Severance,E. G., Yolken, R. H., Xiao, J. C.
Infection and Immunity 2018; 86: DOI: 10.1128/iai.00398-18
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Anti-NMDA receptor (NMDAR) autoantibodies have been postulated to play a role in the pathogenesis of NMDAR hypofunction, which contributes to the etiology of psychotic symptoms. Toxoplasma gondii is a pathogen implicated in psychiatric disorders and associated with elevation of NMDAR autoantibodies. However, it remains unclear whether parasite infection is the cause of NMDAR autoantibodies. By using mouse models, we found that NMDAR autoantibody generation had a strong temporal association with tissue cyst formation, as determined by MAGI antibody seroreactivity (r = 0.96; P < 0.0001), which is a serologic marker for the cyst burden. The presence of MAGI antibody response, but not T. gondii IgG response, was required for NMDAR autoantibody production. The pathogenic relevance of NMDAR autoantibodies to behavioral abnormalities (blunted response to amphetamine-triggered activity and decreased locomotor activity and exploration) and reduced expression of synaptic proteins (the GLUN2B subtype of NMDAR and PSD-95) has been demonstrated in infected mice. Our study suggests that NMDAR autoantibodies are specifically induced by persistent T. gondii infection and are most likely triggered by tissue cysts. NMDAR autoantibody seroreactivity may be a novel pathological hallmark of chronic toxoplasmosis, which raises questions about NMDAR hypofunction and neurodegeneration in the infected brain.
Toxoplasma gondii exposure and the risk of attention deficit hyperactivity disorder in children and adolescents
Khademvatan, S. , Riahi,F., Izadi-Mazidi,M. , Khajeddin, N., Yousefi, E.
Pediatric Infectious Disease Journal 2018; 37: 1097-1100
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Background: Evidence suggests that Toxoplasma gondii, which causes toxoplasmosis, changes the metabolism of neurotransmitters, especially dopamine, resulting in both neurologic and psychiatric disorders. On the other hand, the dysregulation of catecholamines, especially of both norepinephrine and dopamine, has been proposed in the pathophysiology of attention deficit hyperactivity disorder (ADHD). The aim of the present study was to investigate anti-toxoplasma antibodies in children and adolescents with ADHD and compare it with a control group, to determine whether toxoplasmosis is a risk factor for ADHD. Methods: A total of 200 children and adolescents (117 patients with ADHD and 83 individuals without ADHD) participated in the study. Participants were tested for the presence of anti-T. gondii antibodies by enzyme-linked immunosorbent assay. A Parent ADHD Rating Scale and Clinical Global Impression-severity Scale were also completed. Data were analyzed using a (2) test and Fisher exact test. Results: Anti-toxoplasma antibodies were detected in 18.1% of patients with ADHD disorder and 24% of individuals without ADHD. There was no significant difference in seropositivity between the 2 groups (P > 0.05). The number of patients with T. gondii infection in the 3 subgroups was 0, 9 and 12, respectively. The differences in infection rate among subgroups were not statistically significant (P > 0.05). Conclusion: Although not conclusive, the present study does not support the theory that T. gondii is a risk factor for ADHD.
Immunoglobulin sub-class distribution in bipolar disorder and schizophrenia: potential relationship with latent Toxoplasma Gondii infection
Hamdani,N. ,Bengoufa, D. , Godin, O., Doukhan, R.., Le Guen,E., Daban-Huard, C. , Bennabi, M. ,Delavest, M., Lepine, J. P., Boukouaci, W. , Laouamri, H. , Houenou,J., Jamain, S., Richard,J. R. , Lecorvosier, P. , Yolken,R. , Rajagopal, K. , Leboyer, M. , Tamouza, R.
BMC Psychiatry,10.1186/s12888-018-1821-9, Article Number 239
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Background: Immune dysfunction could play a significant role in the pathogenesis of bipolar disorder (BD) and schizophrenia (SZ), conditions with an underlying pro-inflammatory state. Studies on humoral immune responses (which reflects antibody mediated fight against pathogens) in schizophrenia and bipolar disorder are sparse and often providing contradictory results. The aim of this study was to assess humoral immunity in a group of stable bipolar disorder and schizophrenia patients compared to controls by determining total Immunoglobulins and IgG subclasses and to assess their association with latent Toxoplasma gondii and/or CMV infection. Methods: 334 subjects (124 BD, 75 SZ and 135 Healthy Controls [HC]) were included and tested for humoral immunity by determining the total immunoglobulins (IgG,A and M) and IgG subclasses (IgG1, IgG2, IgG3, IgG4) and their relationship with latent Toxoplasma gondii infection, an established risk factor for BD and SZ. Results: Although lower levels of IgG, IgG1, IgG2, IgG4 and IgA were found among BD as compared to HC and/or SZ, after adjustment for confounding variables, only low levels of IgG and IgG1 in BD remai- ned significant. Strikingly highest levels of antibodies to T. gondii (but not CMV) infection in BD and SZ were associated with lowest levels of IgG3 and IgG4 levels as compared to controls. Conclusions: Schizophrenia and bipolar disorder patients with latent T. gondii specific infection may be more vulnerable to changes in immuno-inflammatory processes than controls with similar latent infectious state. Simultaneous sequential immunological monitoring both in steady state and active disease phases in the same BD and SZ patients are warranted to understand the role of Toxoplasma gondii latency in these disorders.
Toxoplasmosis, but not borreliosis, is associated with psychiatric disorders and symptoms – false negative findings?
Hajek, T.
Manuscript Number: SCHRES-D-18-00778
Latent toxoplasma infection in real-world schizophrenia: Results from the national FACE-SZ cohort
Fond,G., Boyer, L. ,Schurhoff, F. ., Berna,F. , Godin, O., Bulzacka, E., Andrianarisoa, M. Brunel, ,L. ,Aouizerate, B. , Capdevielle, D.,Chereau, I. , Coulon, N., D'Amato, T. , Dubertret,C. , Dubreucq, J.,Faget, C.,. Lancon, Leignier,S., Mallet,J., Misdrahi, D., Passerieux, C., Rey,R., Schandrin,A., Urbach,M., Vidailhet,P., Llorca, P. M., Leboyer, M., Grp,F.S.
Schizophrenia Research 2018; 201: 373-380
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Objective: Latent Toxoplasma infection has been associated with widespread brain immune activation, increased blood brain barrier permeability, neural disruption, increased dopamine release in dopaminergic neurons, with NMDA activation and with schizophrenia (SZ) onset risk. Toxoplasma has been suggested to be a source of chronic low-grade inflammation and this inflammation has been associated with cognitive impairment in SZ. The objective of the present study were (i) to determine if latent Toxoplasma infection was associated with specific clinical features in stabilized SZ subjects, with cognitive impairment and with increased low-grade peripheral inflammation and (ii) to determine if Treatments with Anti-Toxoplasmic Activity (TATA) were associated with improved outcomes in subjects with latent Toxoplasma infection. Methods: A comprehensive 2 daylong clinical and neuropsychological battery was administered in 250 SZ subjects included between 2015 and 2017 in the national FondaMental Expert Center (FACE-SZ) Cohort. Solid phase-enzyme microplate immunoassay methods were used to measure IgG class of antibodies to T. gondii in blood sample. Latent Toxoplasma infection was defined by T. gondii IgG ratio >= 0.8, equivalent to >= 10 international units. Chronic peripheral inflammation was defined by highly sensitive Creactive protein blood level >= 3 mg/L. Results: Latent Toxoplasma infection has been found in 184 (73.6%) of this national multicentric sample. In the multivariate analyses, latent Toxoplasma infection has been significantly associated with higher PANSS negative (aOR = 1.1 [1.1-1.1], p = 0.04) and excitement subscores (aOR = 1.3 [1.1-1.6], p = 0.01), with two specific symptoms (i.e., reference delusion (aOR = 3.6 [1.2-10.6] p = 0.01) and alogia (aOR = 16.7 [2.0-134.7], p = 0.008)) and with chronic low-grade peripheral inflammation (27.2% vs. 7.6%, aOR = 3.8 [1.4-10.3], p = 0.004). Extrapyramidal symptoms remained significantly associated with latent Toxoplasma infection. On the opposite, no significant association of latent Toxoplasma infection with age, gender, age at SZ onset, suicide behavior or cognitive deficits has been found in these models (all p > 0.05). TATA were associated with lower depressive symptoms (aOR = 0.8[0.7-0.9], p = 0.01), and with lower rates of chronic peripheral inflammation (20.9% vs. 48.6%, aOR = 3.5 [1.5-7.9], p = 0.003) but not with higher cognitive scores (p > 0.05). Conclusion: The present findings suggest that Toxoplasma is almost 3 times more frequent in SZ population compared to general population in France. The potential cerebral underpinnings of the association of latent Toxoplasma infection and the above-mentioned outcomes have been discussed. Future studies should confirm that TATA may be effective to reduce Toxoplasma-associated depressive symptoms and low-grade peripheral inflammation.
Cytomegalovirus/toxoplasma antibody titers in bipolar disorder
Frye, M. , Coombes, B., McElroy, S. Jones-Brando,,L., Veldic, M. ,Colby, C. ,Bobo W. , Singh,B. , Dickerson, F. Biernacka , J. , Yolken, R.
Bipolar Disorders 2018; 20:122-122
Toxoplasmosis, but not borreliosis, is associated with psychiatric disorders and symptoms MENTAL
Flegr, J., Horáček, J.
Schizophrenia Research 2018; 197: 603-604
Seroprevalence of Toxoplasma gondii infection in children with central nervous system disorders in Mansoura, Egypt: a case-control study
El-Beshbishi,S. N. , El-Tantawy,N. L, Elzeky, S. M., Abdalaziz , K. F. ,Atia, R. A.
Transactions of the Royal Society of Tropical Medicine and Hygiene 2018;112: 555-560
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Background: Toxoplasma gondii is a global infection with a crucial role in the development of neurological diseases. Data concerning the association between T. gondii and neurological illnesses in Egyptian children is scarce. Methods: A case-control study was conducted on 60 patients divided into children suffering from central nervous system manifestations without apparent chromosomal anomalies (n=30) and children with Down syndrome (n=30) recruited from Mansoura University Children's Hospital, Mansoura, Egypt. A total of 30 healthy children were included as controls. Demographics and clinical data were collected from all cases and Toxoplasma immunoglobulin (Ig) M and G antibodies were assessed by enzyme-linked immunosorbent assay. Results: Anti-T. gondii IgG was the most frequent antibody detected and the highest seropositivity rates were ranked for the neurologically disabled non-syndromic children, followed by Down syndrome, compared with controls (p <= 0.001). Statistically significant (p=0.05) associations were found between Toxoplasma IgG seropositivity and hydrocephalus and between Toxoplasma IgM and a history of contact with farm animals, soil and cats in children with Down syndrome. Conclusions: The association between Toxoplasma infection and neurological disorders in children should be kept in mind by paediatricians and assessment of T. gondii antibodies in early childhood is needed for timely management of afflicted patients.
Impact of ApoE genotypes variations on Toxoplasma patients with dementia
Yahya, R. S., Awad, S. I., El-Baz, H. A., Saudy,N., Abdelsalam, O. A., Al-Din, M. S. S.
Journal of Clinical Neuroscience 2017;39:184-188
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Background: Toxoplasma deprives host neuron cells from cholesterol and leads to its ability to potentiate dementia. ApoE intermediates neuronal transmission of cholesterol, which is a key constituent for axonal development, redesigning occasions that are important for education and synaptic arrangement, development of memory and repair of neuron. The aim of this work is to investigate the effect of ApoE genotypes on dementia associated with neurodegeneration in latent Toxoplasma gondii in elderly population. Methods: This study comprised: 133 patients with dementia (78 were positive for toxoplasma IgG and 55 were negative) and 95 subjects as control group without dementia (30 were positive for toxoplasma IgG and 65 were negative). All of them were subjected to a cognitive assessment, T. gondii seropositivity (ELISA) and determination of ApoE allelic forms (PCR). Results: The ApoE genotype distribution shows that the most predominant genotype is ApoE3/3 and the most widely recognized allele is E3. Both patients and control were further divided into Toxoplasma IgG positive group (n = 108) and Toxoplasma IgG negative group (n = 120). ApoE4 non carrier, ApoE 2/3 and ApoE 3/3 alleles have highly significant differences (P < 0.001) between dementia and non-dementia patients in Toxoplasma infected patients in comparison to non-infected ones. Conclusion: Toxoplasma positive patients have more risk to develop dementia regardless ApoE4 carriage. (C) 2017 Elsevier Ltd. All rights reserved.
A critical assessment of the association between postnatal toxoplasmosis and epilepsy in immune-competent patients
Uzorka, J. W., Arend, S. M.
European Journal of Clinical Microbiology and Infectious Diseases 2017; 7:1111-1117
Seroprevalence of Toxoplasma gondii in Romanian psychiatric patients
Olariu, T. R., Capraru, I. D., Papava, I., Romosan, R., Dehelean, L., Lupu, M. A.
European Psychiatry 2017;41:825
Increased prevalence of Toxoplasma gondii seropositivity in patients with treatment-resistant schizophrenia
Sagud, M., Vlatkovic, S., Strac, D. S., Sviben, M., Zivkovic, M., Vilibic, M., Vuksan-Cusa, B., Mihaljevic-Peles, A., Pivac, N.,
European Psychiatry 2017;41:834
Neurophysiological changes induced by chronic Toxoplasma gondii infection
Tedford, E., McConkey, G.
Pathogens 2017; 6: Artn 19 10.3390/Pathogens6020019
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Although the parasite Toxoplasma gondii is one of the most pervasive neurotropic pathogens in the world, the host-parasite interactions during CNS infection and the consequences of neurological infection are just beginning to be unraveled. The chronic stages of infection have been considered dormant, although several studies have found correlations of infection with an array of host behavioral changes. These may facilitate parasite transmission and impact neurological diseases. During infection, in addition to the presence of the parasites within neurons, host-mediated neuroimmune and hormonal responses to infection are also present. T. gondii induces numerous changes to host neurons during infection and globally alters host neurological signaling pathways, as discussed in this review. Understanding the neurophysiological changes in the host brain is imperative to understanding the parasitic mechanisms and to delineate the effects of this single-celled parasite on health and its contribution to neurological disease
Toxoplasmosis, the insidious parasitic infection: dangers of asymptomatic carrier state
Bognar, L., Izso, T., Szakos, D., Kasza, G.
Magyar Allatorvosok Lapja 2017;139:479-487
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Background: The highly prevalent parasitic infection of humans, toxoplasmosis, can have serious consequences even during an asymptomatic course of the disease. The causative agente of infection is Toxoplasma gondii, which proliferates in the intestine of cats. Risk of infection by direct contact with cats is low, but the infection can occur due to contaminated soil, water, unwashed vegetables and fruits, as well as insufficiently heat-treated meat. Objectives: The aim of this study was to synthesize the current knowledge about infection caused by Toxoplasma gondii in a brief review focusing on latent toxoplasmosis in humans. Materials and Methods: More than hundred articles, studies and reports from scientific journals were considered to summarize the infection's characteristics such as prevalence and symptoms in humans. Results and Discussion: The symptoms of acute toxoplasmosis are either featureless, or non-existent, although, for people with immunosuppression it can be fatal, and for expectants it can result in foetal harm. The detection of the infection is conducted with serology methods, however, only in a few European countries are general screenings present. The asymptomatic carrier state is dangerous as well, because the cysts subsist in the brain of the host, which affects behaviour, the regulation of emotions, and also the level of several hormones. The latent toxoplasmosis can be connected to aggression, anxiety, schizophrenia, bipolar personality disorder, suicidal inclination, depression, and the reduction in intelligence quotient. For the reason of the deterioration of reaction time, the disease increases the risk of traffic accidents. The latent toxoplasmosis also influences personality traits; for women and men the alteration of the personality change differs. There is no data on the current epidemiological situation in Hungary, and not even in Europe. A research regarding the extent of asymptomatic carrier state and about the psychological changes in the Hungarian population has not been conducted so far.
Association of Toxoplasma gondii infection with schizophrenia and its relationship with suicide attempts in these patients
Ansari-Lari, M., Farashbandi, H., Mohammadi, F.
Tropical Medicine and International Health 2017; 22: 1322-1327
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OBJECTIVES To investigate the association between schizophrenia and Toxoplasma gondii, and to assess the association of infection with suicide attempts and age of onset of schizophrenia in these patients. METHODS Case-control study Fars Province, southern Iran. Cases were individuals with psychiatric diagnosis of schizophrenia as per Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria. Controls were healthy blood donors, frequency-matched with patients according to age and sex. For the detection of IgG antibodies, enzyme-linked immunosorbent assay (ELISA) was used. Data about demographic information in all subjects and duration of illness and history of suicide attempts in patients with schizophrenia were collected using a brief questionnaire and hospital records. Chi-square test and multivariable logistic regression were used for statistical analyses. RESULTS Among 99 cases, 42 individuals (42%) were positive for T. gondii antibody, vs. 41 (27%) among 152 controls (OR = 2, 95% CI: 1.2-3.4, P = 0.012). We compared the suicide attempts in patients with schizophrenia based on their T. gondii serologic status. There was a lower rate of suicide attempts in seropositive male patients than seronegative ones (OR = 0.3, 95% CI: 0.1-0.97, P = 0.04). Age of onset of schizophrenia did not differ between T. gondii-infected and non-infected patients. CONCLUSIONS These findings may have implications for schizophrenia and suicide prevention programmes. However, clearly further studies are required to confirm them.
Physical and mental health status in Toxoplasma-infected women before and three years after they learn about their infection: Manipulation or side-effects of impaired health?
Šebánková, B., Flegr, J.
Frontiers in Ecology and Evolution 2017; 5:144
Fetomaternal and pediatric toxoplasmosis
Oz, H. S.
Journal of Pediatric Infectious Diseases 2017; 12: 202-208
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Toxoplasmosis is one of the most important causes of foodborne illnesses and inflammatory complications, as well as congenital disorders. Promiscuous Toxoplasma is transmitted by contaminated food and animal produce, water, vegetations, fruits, and sexually through semen. Toxoplasma infects nucleated cells with a unique tropism formuscles and central nervous system and amind bugging malicious effect. Pregnant women with acute or reactivated toxoplasmosis can transmit Toxoplasma via transplacental transmission to the fetus. The severity of congenital toxoplasmosis depends on the gestation period, as infection in early pregnancy causes more severe consequences. Congenital toxoplasmosis complications include miscarriage, encephalitis, neurological retardation, mental illnesses, auditory, and visual inflammatory disorders, cardiovascular abnormalities, and pains. Current therapies are inefficient for congenital and chronic toxoplasmosis or have severe side effects with life-threatening complications. There is an urgent need for effective and safe therapeutic modalities to treat complications of toxoplasmosis and effective vaccines to eliminate the infectious agent. This investigation will discuss the pathogenesis of fetomaternal, congenital, and pediatric toxoplasmosis, the currently available therapies in practice, and explore those therapeutic modalities in experimental stages for promising future trials.
New, previously unreported correlations between latent Toxoplasma gondii infection and excessive ethanol consumption
Samojlowicz, D., Borowska-Solonynko, A., Kruczyk, M.
Forensic Science International 2017; 280: 49-54
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A number of world literature reports indicate that a latent Toxoplasma gondii infection leads to development of central nervous system disorders, which in turn may lead to altered behavior in the affected individuals. T. gondii infection has been observed to play the greatest role in drivers, suicides, and psychiatric patients. Studies conducted for this manuscript involve a different, never before really reported correlation between latent T. gondii infection and ethanol abuse. A total of 538 decedents with a known cause of death were included in the study. These individuals were divided into three groups: the risky behavior group, inconclusively risky behavior group, and control group. The criterion for this division was the likely effect of the individual's behavior on the mechanism and cause of his/her death. The material used for analyses were blood samples collected during routine medico-legal examinations in these cases. The blood samples were used to measure anti-T. gondii IgG antibodies with an enzyme-linked immunosorbent assay (ELISA). Moreover, the following data were recorded for each decedent: sex, age, circumstances of death, cause of death, time from death to autopsy, and (if provided) substance abuse status (alcohol, illicit drugs). In those cases where blood alcohol level or toxicology tests were requested by the Prosecutor's Office, their results were also included in our analysis. Test results demonstrated a strong correlation between latent T. gondii infection and engaging in risky behaviors leading to death. Moreover, analyses demonstrated a positive correlation between the presence of anti-T. gondii IgG antibodies and psychoactive substance (especially ethanol) abuse, however, the causal relationship remains unclear. Due to the fact that alcohol abuse constitutes a significant social problem, searching for eliminable risk factors for addiction is extremely important. Our analyses provided new important information on the possible effects of latent T. gondii infection in humans.
Seroprevalence and manifestations of ocular toxoplasmosis in patients with schizophrenia
Morais, F. B., Arantes, Tefe, Muccioli, C.
Ocular Immunology andI Inflammation 2017: 1-4
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PURPOSE: Recent studies have linked infectious agents such as Toxoplasma gondii to schizophrenia. We investigated the seroprevalence of T. gondii and conducted ophthalmologic examinations in schizophrenia patients and controls to identify lesions suggestive of ocular toxoplasmosis. METHODS: During 2015 and 2016, 34 schizophrenia patients and 85 healthy controls underwent ophthalmologic examination and anti-T. gondii IgG and IgM antibody measurements by chemiluminescence. RESULTS: Schizophrenia patients had a higher prevalence of anti-T. gondii IgG positivity than controls (91.18% [95% confidence interval (CI), 77.04%-96.95%] vs. 70.59% [95% CI, 60.18%-79.21%]; p = 0.017). Anti-T. gondii IgM antibodies (acute form) were not detected in any patient. One (3%) schizophrenic patient and two (2.4%) control patients presented fundoscopic scarring. CONCLUSION: The seropositivity rate was significantly higher among schizophrenia patients than among controls (p = 0.017). There was no association between the presence of fundoscopic scarring and schizophrenia (p = 1.000).
Toxoplasma gondii infection in patients with Alzheimer’s disease and healthy individuals: strange molecular results
Abdoli, A.
International Journal of Geriatric Psychiatry 2017; 32: 585-586
Seroepidemiological study of Toxoplasma gondii infection among psychiatric patients in Mashhad, Northeast of Iran
Abdollahian, E., Shafiei, R., Mokhber, N., Kalantar, K., Fata, A.
Iranian Journal of Parasitology 2017; 12: 117-122
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Background: Psychiatric patients have an increased risk of some infections like toxoplasmosis. Investigations on Toxoplasma gondii infection among psychiatric patients have been limited in Mashhad, Northeast of Iran. In this case-control study, prevalence of T. gondii was investigated by serological method.
Methods: This case-control study was performed among psychiatric patients admitted to Avicenna Hospital in Mashhad, Northeast of Iran. Three hundred and fifty inpatients and 350 controls were examined in 2012-2013 for detection of IgG and IgM antibodies against T. gondii in their blood sera by ELISA. Socio-demographic and clinical manifestations of the patients were obtained.
Results: Anti-T. gondii IgG antibodies was found in 164 (46.85%) of 350 psychiatric inpatients and 120 (34.28%) of 350 controls. Seventeen (4.85%) of psychiatric individuals and 3 (0.85%) of control group were IgM+/IgG-indicating acute form of toxoplasmosis. There were no statistically significant differences between the case and control groups. In patient group, schizophrenic patients had the highest positive rate (46.28%) and bipolar mood disorder had the second most prevalent rate (20%). Of 162 schizophrenia patients, 65 (40.1%) had latent infection which was higher than that observed in controls.
Conclusion: The prevalence of T. gondii infection among psychiatric patients suffering from schizophrenia was more in Mashhad, compared with control group.
Lack of association between Toxoplasma gondii exposure and depression in pregnant women: a case-control study
Alvarado-Esquivel, C., Martinez-Martinez, A. L., Sanchez-Anguiano, L. F., Hernandez-Tinoco, J., Castillo-Orona, J. M., Salas-Martinez, C., Sifuentes-Alvarez, A., Sandoval-Carrillo, A. A., Salas-Pacheco, J. M., Liesenfeld, O., Antuna-Salcido, E. I.
BMC Infectious Diseases 2017; 17: 190
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Background: Very little is known about the link of T. gondii infection and depression. Through an age-, gender-, and month of pregnancy-matched case-control study, we determined the association of T. gondii infection and depression in pregnant women.
Methods: We studied 200 pregnant women with depression and 200 pregnant women without depression attended in a public hospital in Durango City, Mexico. Pregnant women were tested for the presence of antiToxoplasma IgG antibodies using an enzyme-linked immunoassay (EIA), and IgG seropositive women were further tested for the presence of IgM using an EIA. IgM positivity by EIA was further analyzed by enzyme-linked fluorescence assay (ELFA).
Results: Anti-T. gondii IgG antibodies were found in 9 (4.5%) of the 200 cases and in 12 (6.0%) of the 200 controls (OR = 0.73; 95% CI: 0.30-1.79; P = 0.50). The frequency of high (> 150 IU/ml) anti-T. gondii IgG levels was similar in cases and in controls (OR = 1.20; 95% CI: 0.36-4.01; P = 0.75). Two women were positive for IgM by EIA but both were negative by ELFA.
Conclusions: We did not find serological evidence of an association between T. gondii infection and depression in pregnant women attended in a public hospital in Durango City, Mexico. Since an association of T. gondii and depression in pregnancy has been reported in the U.S. previously, further research to elucidate the role of T. gondii in prenatal depression should be conducted.
Toxoplasma gondii exposure and Parkinson’s disease: a case-control study
Alvarado-Esquivel, C., Mendez-Hernandez, E. M., Salas-Pacheco, J. M., Ruano-Calderon, L. A., Hernandez-Tinoco, J., Arias-Carrion, O., Sanchez-Anguiano, L. F., Castellanos-Juarez, F. X., Sandoval-Carrillo, A. A., Liesenfeld, O., Ramos-Nevarez, A.
Bmj Open 2017; 7
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Objectives: To determine the association between Toxoplasma gondii infection and Parkinson's disease and to investigate whether T. gondii seropositivity is associated with the general characteristics of patients with Parkinson's disease.
Design: Case-control study.
Setting: Cases and controls were enrolled in Durango City, Mexico.
Participants: 65 patients with Parkinson's disease and 195 age-and gender-matched control subjects without Parkinson's disease.
Primary and secondary outcome measures: Serum samples of participants were analysed for anti-T. gondii IgG and IgM antibodies by commercially available enzyme-linked immunoassays. Prevalence of T. gondii DNA was determined in seropositive subjects using PCR. The association between clinical data and infection was examined by bivariate analysis.
Results: Anti-T. gondii IgG antibodies were found in 6/65 cases (9.2%) and in 21/195 controls (10.8%) (OR 0.84; 95% CI 0.32 to 2.18; p=0.81). The frequency of high (>150 IU/mL) antibody levels was similar among cases and controls (p=0.34). None of the anti-T. gondii IgG positive cases and four of the anti-T. gondii IgG positive controls had anti-T. gondii IgM antibodies (p=0.54). The prevalence of T. gondii DNA was comparable in seropositive cases and controls (16.7% and 25%, respectively; p=1.0). Seroprevalence of T. gondii infection was associated with a young age onset of disease (p=0.03), high Unified Parkinson Disease Rating Scale scores (p=0.04) and depression (p=0.02). Seropositivity to T. gondii infection was lower in patients treated with pramipexole than in patients without this treatment (p=0.01). However, none of the associations remained significant after Bonferroni correction.
Conclusions: The results do not support an association between T. gondii infection and Parkinson's disease. However, T. gondii infection might have an influence on certain symptoms of Parkinson's disease. Further research to elucidate the role of T. gondii exposure on Parkinson's disease is warranted.
Toxoplasma gondii affects posterior association cortex and related functions in healthy, but not schizophrenia. individuals
Cobia, D., Perry, C., Gale, S., Hedges, D., Smith, M., Wang, L., Csernansky, J.
Schizophrenia Bulletin 2017; 43: S141-S141
Is there any association between Toxoplasma gondii infection and bipolar disorder? A systematic review and meta-analysis
de Barros, Jlvm, Barbosa, I. G., Salem, H., Rocha, N. P., Kummer, A., Okusaga, O. O., Soares, J. C., Teixeira, A. L.
Journal of Affective Disorders 2017; 209: 59-65
Is Toxoplasma gondii a trigger of bipolar disorder?
Del Grande, C., Galli, L., Schiavi, E., Dell'Osso, L., Bruschi, F.,
Pathogens 2017, 6(1), 3; doi:10.3390/pathogens6010003
Parkinson’s disease and Toxoplasma gondii infection: Sero-molecular assess the possible link among patients
Fallahi, S., Rostami, A., Birjandi, M., Zebardast, N., Kheirandish, F., Spotin, A.
Acta Tropica 2017; 173: 97-101
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We investigated the possible association between Parkinson's disease (PD), the second most common neurode-generative disorder and Toxoplasma gondii infection, the most common neurotropic protozoan parasitic infection, using serological and molecular techniques. One hundred and fifteen patients with confirmed PD and 115 healthy subjects in the same age and sex distribution were enrolled in this study. Blood samples were taken from each participant and the sera was screened for anti-Toxoplasma antibodies (IgG and IgM). PCR assay was performed in duplicate using the primer pair targeting the B1 gene of Toxoplasma. Amplicons were directly sequenced to conduct the phylogenetic analysis. The prevalence of Toxoplasma infection based on IgG titer was 53% in case and 55.6% in the control groups, revealing no statistically significant association between Toxoplasma seropositivity and PD (OR = 0.90; 95% CI = 0.54-1.51; P = 0.691). According to PCR assay, the prevalence of Toxoplasma infections was 19.3% in the case and 10.4% in control groups which the difference was statistically significant (OR = 3.02; 95% CI = 1.46-6.27; P = 0.002). Multiple sequence alignment of Toxoplasma gondii isolates manifested a common haplotype by the identity: 93.6-100% and divergence: 0-6.7%. We concluded that T. gondii infection not only could not be a risk factor to PD, but even it could be concluded that patients with PD are in more risk to acquisition of infection. These results provide fresh insights into the ambiguous association between T. gondii infection and PD.
Toxoplasma gondii and schizophrenia: a review of published RCTs
Chorlton, S.D.
Parasitology Research 2017; 116: 1793-1799
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Over the last 60 years, accumulating evidence has suggested that acute, chronic, and maternal Toxoplasma gondii infections predispose to schizophrenia. More recent evidence suggests that chronically infected patients with schizophrenia present with more severe disease. After acute infection, parasites form walled cysts in the brain, leading to lifelong chronic infection and drug resistance to commonly used antiparasitics. Chronic infection is the most studied and closely linked with development and severity of schizophrenia. There are currently four published randomized controlled trials evaluating antiparasitic drugs, specifically azithromycin, trimethoprim, artemisinin, and artemether, in patients with schizophrenia. No trials have demonstrated a change in psychopathology with adjunctive treatment. Published trials have either selected drugs without evidence against chronic infection or used them at doses too low to reduce brain cyst burden. Furthermore, trials have failed to achieve sufficient power or account for confounders such as previous antipsychotic treatment, sex, age, or rhesus status on antiparasitic effect. There are currently no ongoing trials of anti-Toxoplasma therapy in schizophrenia despite ample evidence to justify further testing.
The association between Toxoplasma and the psychosis continuum in a general population setting
Lindgren, M., Torniainen-Holm, M., Yolken, R., Suvisaari, J.
Schizophrenia Bulletin 2017; 43: S108-S109
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Background: An increased prevalence of antibodies to Toxoplasma gondii has been found to be associated with psychosis. An association with positive symptom severity in a psychosis risk sample has also been reported. However, the possible association between toxoplasma and positive symptoms in the general population is unknown.
Methods: We investigated whether Toxoplasma gondii is associated with psychosis diagnoses and psychotic symptoms in the general population. We used data from Health 2000, a large health survey of the Finnish population aged 30 and older (n = 5906). Levels of IgG antibodies to Toxoplasma gondii were determined and seropositivity defined as a cutoff of 50 IU/ml.
Lifetime psychotic symptoms were identified with section G of the Composite International Diagnostic Interview, Munich version (M-CIDI). The CIDI screen was considered positive if the interviewee reported any clinically relevant symptom or at least 3 symptoms regardless of clinical relevance.
Lifetime psychotic disorders were screened from the sample and were diagnosed with DSM-IV using case notes and SCID-I interview. The possible diagnoses were: any psychotic disorder, functional psychosis, schizophrenia, other nonaffective psychosis, and affective psychosis.
Results: The seroprevalence of Toxoplasma in the population was 13%; 12% of the participants reported at least one psychotic symptom, the most common symptoms being delusions of reference and suspicion, and 4% were considered positive for the CIDI screen.
In a logistic regression model, toxoplasma seropositivity was the only significant predictor of the CIDI screen status, when other variables associated with toxoplasma were adjusted for (age, gender, education, region of residence, cat ownership, and C-reactive protein measuring inflammation).
Toxoplasma infection was not associated with any psychosis diagnoses.
Conclusion: In a large sample representing the whole Finnish population aged 30 and older, we found that toxoplasma infection predicted psychotic symptoms but not psychosis diagnoses. The association between psychotic symptoms and toxoplasma was not explained by inflammation.
Genome-wide association study (GWAS) of Toxoplasma gondii infection and evaluation of schizophrenia risk by using a polygenic risk score (PRS)
Lori, A., Avramopoulos, D., Wang, A., Goes, F. S., Mulle, J., Powers, A., McGrath, J. J., Massa, N., Weng, L., Duncan, E., Nestadt, G., Conneely, K., Wolyniec, P., Wang, R., Hopkins, M., Ruczinski, I., Yolken, R., Jovanovic, T., Ressler, K., Pulver, A. E., Pearce, B. D.
Biological Psychiatry 2017; 81: S371-S371
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Toxoplasma gondii (TOXO) infects approximately 1.5 billion people worldwide. TOXO is implicated in a heightened risk for schizophrenia (SCZ). We performed a GWAS with TOXO in an Ashkenazi cohort of SCZ subjects. We then applied the schizophrenia polygenic risk score (SCZ-PRS) derived from the Psychiatric GWAS Consortium separately in TOXO-positive and TOXO-negative subjects to explore the hypothesis that SCZ subjects infected by TOXO will have less polygenic risk burden than uninfected subjects.
From toxoplasmosis to schizophrenia via nMda dysfunction: peptide overlap between Toxoplasma gondii and N-Methyl-D-aspartate receptors as a potential Mechanistic Link.
Lucchese, G.
Frontiers in Psychiatry 2017; 8
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The present work aims at investigating how Toxoplasma gondii (T. gondii) infection may be linked to N-methyl-D-aspartate receptor (NMDAR) dysfunction in schizophrenia and related disorders and puts forward the hypothesis that immune responses against T. gondii may involve NMDARs. Indeed, the analysis of the protozoan proteome and NMDAR subunits for peptide commonalities shows a massive peptide overlap and supports the possibility that anti-T. gondii immune responses raised during active protozoan infection may cross-react with host NMDARs, determining disruption of neural circuits and cognitive deficits. In particular, the NMDA 2D subunit, which is mainly expressed in parvalbumin-positive interneurons, appears to be a hotspot for potential T. gondii-induced cross-reactive immune attacks.