Toxoplasmosis and Other Diseases
It appears that increased antibodies to T. gondii are not specific to schizophrenia. A study of 199 patients with bipolar disorder reported an increased prevalence compared to controls.1 This finding was subsequently replicated in a smaller American sample (n=41).2 It was also replicated in a French sample of 110 bipolar disorder patients and 106 healthy controls (OR=2.2, p=0.028).3 In this French sample seropositivity to T. gondii correlated with cognitive deterioration and elevated levels of interleukin-6.4 Yet another study from Brazil reported a significant increase in T. gondii seropositivity in a small sample of patients with mood disorder (n=28, including 24 bipolar and 14 major depression) compared to healthy controls (n=95).5 In a small study, maternal T. gondii IgG antibodies were not associated with bipolar disorder in the offspring.6
Studies examining the possible relationship between infection with T. gondii and bipolar disorder date to at least 1980.7 In recent years, two meta-analyses have been published, including the above studies. Sutterland et al identified 11 studies with a total of 1,163 bipolar patients and reported a significant OR of 1.52 (95% CI 1.06-2.18, p = 0.02).8 There was no significant publication bias but heterogeneity was high. The second meta-analysis, by de Barres et al, included 8 studies, 3 of which had not been included in the first meta-analyses. They included 797 bipolar patients with an OR of 1.26 (95% CI 1.08-1.47). Also of interest is an impressive case study describing “a relationship between ocular manifestations [of toxoplasmosis] and the clinical course of bipolar disorder, confirmed by molecular analyses (nested-PCR), as well as by the high level of T. gondii specific IgG”.9 Also of interest are two studies looking at the intersection of genes with T. gondii in causing bipolar disorder; in both studies the samples were too small.10
Major Depression and Suicide Attempts
Sutherland et al8 carried out a meta-analysis of 9 studies with 1,462 subjects that examined antibodies to T. gondii in individuals with major depression. They reported a non-significant association (OR 1.21; CI 0.86-1.70) with high heterogeneity. The heterogeneity was largely due to a Chinese study that had an OR of 2.41; Sutherland et al speculated that the Chinese study was different because it included subjects with depression with psychotic features. Sutherland’s negative findings regarding toxoplasmosis and major depression are supported by two population-based studies involving 48411 and 1846 subjects12; both failed to find any association between toxo seropositivity and depressive symptoms. Since the 2012 publication of the Sutherland et al meta-analysis, three additional studies involving 7013; 32514 and 41415 subjects all reported significant associations between toxo seropositivity and symptoms of depression but another study16 did not.
Eight studies have assessed serological status to T. gondii in individuals who have attempted or completed suicide. Yagmur et al (n=400), Zhang et al (n = 84), and Okusaga et al (n = 950) all reported significantly higher toxo seropositivity rates in suicide attempters compared to controls, although in the latter study that was only true for younger individuals.17-19 Dickerson et al (n= 162) reported an elevated rate for those with toxo IgM but not IgG antibodies.20 Three other studies (n=320, 283, and 108) reported that the rate of seropositivity between suicide attempters and controls did not differ but rather that those who had attempted suicide had significantly higher T. gondii IgG titres.21-23 In Denmark individuals who had had congenital toxoplasmosis, as assessed by having antibodies at birth, were significantly more likely to attempt and complete suicide as adults.24 And in Poland a postmortem study found higher rates of toxo seropositivity among individuals ages 38 to 58 who died by suicide compared to those who died from various medical conditions.25 Finally, two studies have reported a correlation between national rates of suicide and rates of toxo seropositivity.26
Two studies examined antibodies to T gondii in individuals diagnosed with obsessive compulsive disorder (OCD). In Turkey 42 individuals with OCD had a significantly higher prevalence of IgG antibodies than 100 controls (p<0.01).27 In China a study comparing 29 individuals with OCD and 445 controls reported no significant difference.28 A study in the Czech Republic used questionnaire information from 1,275 individuals to link self-reported toxo seropositivity to a higher score on an OCD inventory.29 Case reports also linked OCD to acquired toxoplasmosis in two children.30
A study of a large community cohort in Detroit reported that T. gondii seropositivity was associated with a diagnosis of general anxiety disorder but not with PTSD or depression.31 Another study of 414 pregnant women reported that the 44 women with antibodies to T. gondii were more likely to be depressed and anxious.32 However, a study of 1,846 American adults reported no significant association between T. gondii seropositivity and general anxiety disorder, panic disorder, or major depressive disorder.33
Three studies have reported the prevalence of toxo seropositivity among substance abusers. Studies of IV drug users in Vietnam (n = 300) and Spain (n = 647) both reported an elevated IgG antibodies.34-35 However a Mexican study of 149 alcohol and drug abusers and 149 controls reported no significant difference in T. gondii antibodies.36
Intermittent Explosive Disorder
A study of 110 individuals with intermittent explosive disorder reported that 22% had antibodies to T. gondii compared to 9% of controls (p=0.05).37
In 1953 Kozar was the first to report a high prevalence of antibodies to T. gondii in individuals with epilepsy [Kozar, previous]. Since 1995 six studies have been published looking for an association between toxoplasmosis and epilepsy. A 2015 meta-analysis of these studies, with a total of 1,280 subjects with epilepsy and 1,608 controls, reported a positive association with an OR of 2.25 (95% CI 1.27-3.90), p = 0.005. The authors concluded that “despite the limited number of studies, and lack of high quality data toxoplasmosis should continue to be regarded as an epilepsy risk factor.38 A previous meta-analysis, that included only the first three studies, had reported an OR of 4.8 (CI 2.6-7.8).39
The first study of T. gondii exposure and brain neoplasms, published in 1967, reported that 71 of 126 individuals (56%) with brain tumors were dye-test positive compared to 52 of 126 (41%) controls (p = 0.02). The highest rate of positivity was among gliomas.40 In 1993 an attempt to replicate this using ELISA to assess T. gondii antibodies in 117 individuals with gliomas, 53 with meningioma, and 415 controls failed to replicate the association in gliomas but reported a positive association in meningiomas (p=0.02).41 More recently two epidemiological studies have been carried out comparing rates of T. gondii seropositivity with the incidence of brain cancers. The first reported a positive association across 37 countries (p<0.0001)42 and the second reported similar findings for 22 administrative regions in France, more pronounced in men and in older people.43
A small study of Alzheimer’s disease in Turkey reported a significantly higher seropositivity for T. gondii among patients than controls.44 A second study in Iran also reported a positive association but there were questions regarding the proper interpretation of the data.45-46 Another study from Iran was negative.47
One study of patients with Parkinson’s disease reported an increase in T. gondii antibodies48, but three other studies did not.49-51
Still other neurological studies have linked T. gondii antibodies to migraine.52
A study of 163 individuals with MS reported no association with T. gondii antibodies.53
In a Finnish study of 874 individuals with autism, it was reported that women who had a high maternal T. gondii IgM level had a significantly decreased odds of having a child with autism.54
Perhaps the most interesting association of T. gondii with other diseases is with rheumatoid arthritis. Six studies have reported an increased prevalence of T. gondii antibodies in individuals with this disease.55-60 Another study reported that individuals with rheumatoid arthritis compared to controls have had more exposure to cats.61 This association is especially interesting because rheumatoid arthritis and schizophrenia share many epidemiological features and it has been noted in many studies that the two diseases are mutually exclusive, i.e., once you get either rheumatoid arthritis or schizophrenia, you almost never get the other.62 This suggests that T. gondii or another pathogen may cause both diseases with the clinical outcome differing because of genetic predisposition, timing of the initial infection, strain difference, or other.
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- Del Grande C, et al. Bipolar disorder with psychotic features and ocular toxoplasmosis. 2017. J Nervous Ment Dis. 2017; 205: 192-195.
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