Are some cases of psychosis caused by microbial agents? A review of the evidence.

Mol Psychiatry. 2008 May;13(5):470-9. Epub 2008 Feb 12.

Are some cases of psychosis caused by microbial agents? A review of the evidence.



The Stanley Laboratory of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins University Medical Center, Baltimore, MD 21287-4933, USA.


The infectious theory of psychosis, prominent early in the twentieth century, has recently received renewed scientific support. Evidence has accumulated that schizophrenia and bipolar disorder are complex diseases in which many predisposing genes interact with one or more environmental agents to cause symptoms. The protozoan Toxoplasma gondii and cytomegalovirus are discussed as examples of infectious agents that have been linked to schizophrenia and in which genes and infectious agents interact. Such infections may occur early in life and are thus consistent with neurodevelopmental as well as genetic theories of psychosis. The outstanding questions regarding infectious theories concern timing and causality. Attempts are underway to address the former by examining sera of individuals prior to the onset of illness and to address the latter by using antiinfective medications to treat individuals with psychosis.
The identification of infectious agents associated with the etiopathogenesis of schizophrenia might lead to new methods for the diagnosis, treatment and prevention of this disorder.


PMID: 18268502 [PubMed – indexed for MEDLINE]

Mood and anxiety disorders in women with treated hyperthyroidism and ophthalmopathy caused by Graves’ disease.

Gen Hosp Psychiatry. 2005 Mar-Apr;27(2):133-9.

Mood and anxiety disorders in women with treated hyperthyroidism and ophthalmopathy caused by Graves’ disease.

Bunevicius R, Velickiene D, Prange AJ Jr.

Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7160, USA.

OBJECTIVE: To evaluate the prevalence of mood and anxiety disorders in women with treated hyperthyroidism caused by Graves’ disease and to compare them with the prevalence of such findings in women without past or present thyroid disease.
METHODS: Thirty inpatient women with treated hyperthyroidism and ophthalmopathy caused by Graves’ disease and 45 women hospitalized for treatment of gynecologic disorders such as abnormal vaginal bleeding, benign tumors or infertility were evaluated for the prevalence of mood and anxiety diagnoses using a standard Mini-International Neuropsychiatric Interview and for mood and anxiety ratings using the Profile of Mood States (POMS). At the time of assessment, it was discovered that 14 of 30 women with treated hyperthyroidism caused by Graves’ disease were still hyperthyroid, while 16 women were euthyroid.
RESULTS: Significantly greater prevalence of social anxiety disorder, generalized anxiety disorder, major depression and total mood and anxiety disorders, as well as higher symptom scores on the POMS, was found in hyperthyroid women with Graves’ disease in comparison with the control group. A prevalence of total anxiety disorder, as well as history of mania or hypomania and lifetime bipolar disorder, but not lifetime unipolar depression, was more frequent in both the euthyroid and the hyperthyroid subgroups of study women in comparison with the control group.
CONCLUSIONS: These results confirm a high prevalence of mood and anxiety disorders in women with treated hyperthyroidism and ophthalmopathy caused by Graves’ disease. Hyperthyroidism plays a major role in psychiatric morbidity in Graves’ disease.
PMID: 15763125 [PubMed – indexed for MEDLINE]

[Manic-depressive symptom associated with endocrine and metabolic disorders]

Nippon Rinsho. 1994 May;52(5):1311-7.
[Manic-depressive symptom associated with endocrine and metabolic disorders]
[Article in Japanese]
Yamada T.
Kashiwa City Hospital.
In an attempt to study “manic-depressive” affairs associated with endocrine and mental disorders, our clinical data are analyzed before and after appropriate treatment in Cushing’s disease, Cushing’s syndrome, hyperthyroid Graves’ disease and primary hypothyroidism. Although our data do not provide definite findings on manic-depressive affairs associated with Cushing’s disease and syndrome, review data by others indicated a high incidence of depression under untreated condition and its disappearance after appropriate treatment.
In contrast, patients with adrenocortical insufficiency did have a depression but this was cleared after supplemental therapy. In hyperthyroid Graves’ disease, a number of emotional and mental instability and irritability were noticed before the treatment, but these abnormalities all disappeared after appropriate treatment for 3-6 months. In contrast, patients with primary hypothyroidism did show lethargy and apathy, and these abnormalities disappeared after appropriate treatment.
From the data accumulated, it is concluded that adrenal steroid and thyroid hormone do affect the functions of nervous system and, as a result, cause a number of clinical symptoms. The exact biochemical processes underlying these abnormalities are not known and remains for further investigations.
PMID: 8007407 [PubMed – indexed for MEDLINE]

Toxoplasma gondii and Schizophrenia


E. Fuller Torrey* and Robert H. Yolken†*Stanley Medical Research Institute, Bethesda, Maryland, USA; and †Johns Hopkins University Medical Center, Baltimore, Maryland, USA
Suggested citation for this article: Torrey EF, Yolken RH. Toxoplasma gondii and schizophrenia.
Emerg Infect Dis [serial online] Nov 2003 [date cited]. Available from: URL:
Recent epidemiologic studies indicate that infectious agents may contribute to some cases of schizophrenia. In animals, infection with Toxoplasma gondii can alter behavior and neurotransmitter function. In humans, acute infection with T. gondii can produce psychotic symptoms similar to those displayed by persons with schizophrenia. Since 1953, a total of 19 studies of T. gondii antibodies in persons with schizophrenia and other severe psychiatric disorders and in controls have been reported; 18 reported a higher percentage of antibodies in the affected persons; in 11 studies the difference was statistically significant. Two other studies found that exposure to cats in childhood was a risk factor for the development of schizophrenia. Some medications used to treat schizophrenia inhibit the replication of T. gondii in cell culture. Establishing the role of T. gondii in the etiopathogenesis of schizophrenia might lead to new medications for its prevention and treatment.
Schizophrenia is a pervasive neuropsychiatric disease of uncertain cause that affects approximately 1% of the adult population in the United States and Europe. An increased occurrence of schizophrenia in family members of affected persons suggests that genetic factors play a role in its etiology, and some candidate predisposing genes have been identified. Environmental factors are also important. Epidemiologic studies, for example, have established that winter-spring birth, urban birth, and perinatal and postnatal infection are all risk factors for the disease developing in later life. These studies have rekindled an interest in the role of infectious agents in schizophrenia, a concept first proposed in 1896 (1). This review focuses on evidence specifically linking infection with Toxoplasma gondii to the etiology of some cases of schizophrenia.
T. gondii is an intracellular parasite in the phylum Apicomplexa. Its life cycle can be completed only in cats and other felids, which are the definitive hosts. However, T. gondii also infects a wide variety of intermediate hosts, including humans. In many mammals, T. gondii is known to be an important cause of abortions and stillbirths and to selectively infect muscle and brain tissue. A variety of neurologic symptoms, including incoordination, tremors, head-shaking, and seizures, have been described in sheep, pigs, cattle, rabbits, and monkeys infected with T. gondii (2).
Humans may become infected by contact with cat feces or by eating undercooked meat. The importance of these modes of transmission may vary in different populations (3). Individual response to Toxoplasma infection is determined by immune status, timing of infection, and the genetic composition of the host and the organism (4).
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Med Sci (Paris). 2009 Aug-Sep;25(8-9):687-91.
[Schizophrenia and toxoplasmosis]
[Article in French]
Dion S, Barbe PG, Leman S, Camus V, Dimier-Poisson I.
Université François Rabelais de Tours, INRA , France.
Schizophrenia is one of the most severe and disabling psychiatric disease that affects about 1 % of the adult worldwide population. Aetiology of schizophrenia is still unknown but genetic and environmental factors are suspected to play a major role in its onset. Recent epidemiologic studies indicate that infectious agents may contribute to some cases of schizophrenia. In particular, several epidemiological, behavioural and neurochemical studies suggested the existence of an association between schizophrenia and past history of primo-infection by the Toxoplasma gondii. However, they are some limitations for this hypothesis among which the lack of correlation between the geographic distribution of both diseases and of direct evidence for the presence of the parasite in schizophrenic patients. Nevertheless the identification of physiopathological mechanisms related to the parasite could provide a better comprehension to the outcome of schizophrenia. Studies on the link between toxoplasmosis and schizophrenia may provide interesting data for the diagnosis and the development of new treatments for this disorder.
PMID: 19765381 [PubMed – indexed for MEDLINE]


Microbes Infect. 2009 Nov;11(13):1011-8. Epub 2009 Jul 26.

Serological pattern consistent with infection with type I Toxoplasma gondii in mothers and risk of psychosis among adult offspring.
Xiao J, Buka SL, Cannon TD, Suzuki Y, Viscidi RP, Torrey EF, Yolken RH.

The Stanley Division of Developmental Neurovirology, Johns Hopkins School of Medicine, 600 N. Wolfe Street, 1105 Blalock, Baltimore, MD 21287-4933, USA.

Previous studies have shown that maternal antibodies to Toxoplasma measured during pregnancy are associated with an increased risk of schizophrenia and other psychoses in adult offspring. Recently, it has been recognized that different genotypes of Toxoplasma have distinct neuropathogenic potential. The objective of this study was to investigate whether parasite genotype is a contributing factor to disease risk. We have developed an enzyme-linked immunosorbent assay (ELISA) that uses polymorphic polypeptides specific to the three clonal parasite lineages and derived from three dense granule antigens, GRA5, GRA6 and GRA7. We used this assay to measure type-specific antibodies in the sera from 219 pregnant women whose children developed schizophrenia and affective psychotic illnesses in adult life, and 618 matched unaffected control mothers from three cohorts of the Collaborative Perinatal Project. We found that the offspring of mothers with a serological pattern consistent with Toxoplasma type capital I, Ukrainian infection were at significantly increased risk for the development of psychoses as compared with the matched unaffected control mothers (odds ratio=1.94; 95% confidence interval=1.08-3.46; p=0.03). The risk was particularly elevated for affective psychoses (OR=5.24; 95% CI=1.67-16.5; p=0.005). In contrast, we did not find an association between maternal antibodies to other genotypes and risk of psychoses in the offspring. These findings suggest an influence of the parasite genotype on increased risk of psychosis and provide further support for a substantive role of Toxoplasma in the etiology of psychosis.
PMID: 19638313 [PubMed – in process]


Parasitol Res. 2009 Oct;105(4):893-8. Epub 2009 Jun 23.

Toxoplasma gondii: host-parasite interaction and behavior manipulation.

da Silva RC, Langoni H.
Department of Veterinary Hygiene and Animal Science, College of Veterinary Medicine and Animal Science, São Paulo State University, Campus of Botucatu, Botucatu, São Paulo, Brazil.

Toxoplasma gondii is an obligate intracellular parasite that causes different lesions in men and other warm-blooded animals. Humoral and cellular immune response of the host against the parasite keeps the protozoan in a latent stage, and clinical disease ensues when immunological response is compromised. Brain parasitism benefits the parasite causing behavioral changes in the host, not only in animals but also in humans. Schizophrenia and epilepsy are two neurological disorders that have recently been reported to affect humans coinfected with T. gondii. Further studies based on host-parasite interaction in several wild or domestic warm-blooded species are still necessary in order to better understand parasitism and behavioral changes caused by T. gondii.

PMID: 19548003 [PubMed – indexed for MEDLINE]