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Toxoplasma gondii & Human Phenotype

Compendium of Known Effects and Ongoing Research

affective disorder

Association of Cytomegalovirus and Toxoplasma gondii Antibody Titers With Bipolar Disorder

January 29, 2020
Frye, M. A., Coombes, B. J., McElroy, S. L., Jones-Brando, L., Bond, D. J., Veldic, M., Romo-Nava, F., Bobo, W. V., Singh, B., Colby, C., Skime, M. K., Biernacka, J. M., Yolken, R
Jama Psychiatry 2019, 76: 1285 - 1293
Click for abstract
Importance Infection-associated immune activation and inflammation are increasingly recognized in the pathophysiology of bipolar disorder. Objective To determine whether antibodies to common infectious agents, including cytomegalovirus (CMV), Toxoplasma gondii, and measles, as well as the inflammatory marker C-reactive protein, in serum samples differ between patients with bipolar disorder and control individuals without bipolar disorder. Design, Setting, and Participants In this case-control study, antibody titers were measured in serum samples from 1207 patients with bipolar disorder and 745 controls that were obtained from biobanks with participating sites in Rochester and Minneapolis, Minnesota (n = 1537), and Cincinnati, Ohio (n = 415), from January 5, 2009, through May 12, 2014. A subset of case patients and controls from Minnesota were matched by age, sex, and educational level. Bipolar type, age at onset, and history of psychosis were assessed for case patients as well as current drug treatment at the time of blood sample obtainment from the biobank. Data were analyzed from February 5, 2018, to January 4, 2019. Exposures The CMV and T gondii antibodies with IgM titers were expressed as z scores and IgG titers dichotomized into seropositive and seronegative based on expected prevalence in the US population and further classified based on the joint CMV-positive/T gondii-negative IgG status, C-reactive protein z score, and drug treatments with antitoxoplasma activity. Main Outcomes and Measures Patients were stratified by bipolar disorder type I or type II, nonearly (>19 years of age) and early (<= 19 years of age) onset, and history of psychosis during mania or no psychosis. Results Of 1207 patients with bipolar disorder (mean [SD] age, 43.2 [15.1] years; 742 [61.5%] female), the CMV-positive/T gondii-negative IgG status was significantly higher (odds ratio [OR], 1.33; 95% CI, 1.09-1.62; P = .004) compared with that in the 745 controls (mean [SD] age, 44.5 [15.5] years; 444 [59.6%] female). The CMV-positive/T gondii-negative IgG status was associated with bipolar cases type I (OR, 1.41; 95% CI, 1.14-1.75; P = .001), nonearly age at onset (OR, 1.41; 95% CI, 1.16-1.72; P = .001), and history of manic psychosis (OR, 1.46; 95% CI, 1.13-1.88; P = .004). Patients with bipolar disorder who received drug treatment with antitoxoplasma activity (n = 272) had significantly lower T gondii IgM titers (median, 1.59; interquartile range, 1.30-2.07) compared with those (n = 900) who did not receive this treatment (median, 1.69; interquartile range, 1.35-2.25) (P = .03). Conclusions and Relevance In this sample, increased long-term antibody response to CMV and decreased long-term antibody response to T gondii were associated with bipolar disorder and the subphenotypes of bipolar type I, nonearly disease onset, and manic psychosis. Further work appears to be needed to better understand genetic vs environmental disease risk and infection or immune activation contribution to overall disease pathogenesis with particular reference to disease onset. This case-control study analyzes the association of long-term antibody response to cytomegalovirus, Toxoplasma gondii, and measles and of C-reactive protein level with bipolar disorder. Question Is bipolar disorder associated with exposure to infectious agents with immune activation? Findings In this case-control study of 1952 patient cases, cytomegalovirus IgG was significantly increased and toxoplasma IgG was significantly decreased among patients with bipolar disorder compared with control individuals. Patients with bipolar disorder who received drug treatment with antitoxoplasma activity had significantly lower toxoplasma IgM titers compared with those not receiving this treatment. Meaning Increased and decreased long-term antibody response to cytomegalovirus and toxoplasma, respectively, were associated with bipolar disorder in this sample; further work appears to be needed to better understand genetic vs environmental risk of the disease and how infection or immune activation contributes to overall disease pathogenesis with particular reference to disease onset.

Tagged: affective disorder, Schizophrenia

Mental health

Toxoplasma gondii as a risk factor for early-onset schizophrenia: Analysis of filter paper blood samples obtained at birth

October 27, 2007
Bo Mortensen P, Norgaard-Pedersen, B Waltoft, B.L., Sorensen, T.L., Hougaard, D., Torrey, E. E., Yolken, R.H.
Biological Psychiatry 2007; 61: 688-693.
Click for abstract
Background: Infections during fetal life or neonatal period, including infections with Toxoplasma gondii, may be associated with a risk for schizophrenia and other mental disorders. The objectives of this study were to study the association between serological markers for maternal and neonatal infection and the risk for schizophrenia, related psychoses, and affective disorders in a national cohort of newborns. Methods: This study was a cohort-based, case-control study combining data from national population registers and patient registers and a national neonatal screening biobank in Denmark. Patients included persons born in Denmark in 1981 or later followed up through 1999 with respect to inpatient or outpatient treatment for schizophrenia or related disorders (ICD-10 F2) or affective disorders (ICD-10 F3). Results: Toxoplasma gondii immunoglobulin G (IgG) levels corresponding to the upper quartile among control subjects were significantly associated with schizophrenia risk (odds ratio [OR] = 1.79, p =.045) after adjustment for urbanicity of place of birth, year of birth, gender, and psychiatric diagnoses among first-degree relatives. There was no significant association between any marker of infection and other schizophrenia-like disorders or affective disorders. Conclusions: Our study supports an association between Toxoplasma gondii and early-onset schizophrenia. Further studies are needed to establish if the association is causal and if it generalizes to cases with onset after age 18.

Tagged: adult schizophrenia, affective disorder, antibodies, family-history, individuals, infections, maternal exposure, neonatal, prenatal influenza, psychosis, register, Schizophrenia, Toxoplasma gondii, viral encephalitis

Mental health

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