Category Archives: Medical Condition Induced Psychosis

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: http://www.cdc.gov/ncidod/EID/vol9no11/03-0143.htm
 
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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SCHIZOPHRENIA AND TOXOPLASMOSIS

 
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. sarah.dion@univ-tours.fr
 
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]

TOXOPLASMA GONDI IN MOTHERS AND RISK OF PSYCHOSIS AMONG ADULT OFFSPRING

 
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]

SCHIZOPHRENIA AND EPILEPSY REPORTED TO AFFECT HUMANS COINFECTED WITH T. GONDII

 
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. silva_rcd@yahoo.com.br

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]

NEUROPSYCHIATRIC DISEASE AND TOXOPLASMA GONDII INFECTION

 
Neuroimmunomodulation. 2009;16(2):122-33. Epub 2009 Feb 11.
Neuropsychiatric disease and Toxoplasma gondii infection.

Henriquez SA, Brett R, Alexander J, Pratt J, Roberts CW.
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 27 Taylor Street, Glasgow, UK.

Toxoplasma gondii infects approximately 30% of the world’s population, but causes overt clinical symptoms in only a small proportion of people. In recent years, the ability of the parasite to manipulate the behaviour of infected mice and rats and alter personality attributes of humans has been reported. Furthermore, a number of studies have now suggested T. gondii infection as a risk factor for the development of schizophrenia and depression in humans. As T. gondii forms cysts that are located in various anatomical sites including the brain during a chronic infection, it is well placed anatomically to mediate these effects directly. The T. gondii genome is known to contain 2 aromatic amino acid hydroxylases that potentially could directly affect dopamine and/or serotonin biosynthesis. However, stimulation of the immune response has also recently been associated with mood and behavioural alterations in humans, and compounds designed to alter mood, such as fluoxetine, have been demonstrated to alter aspects of immune function. Herein, the evidence for T.-gondii-induced behavioural changes relevant to schizophrenia and depression is reviewed. Potential mechanisms responsible for these changes in behaviour including the role of tryptophan metabolism and the hypothalamic-pituitary-adrenal axis are discussed. Copyright (c) 2009 S. Karger AG, Basel.
 
PMID: 19212132 [PubMed – indexed for MEDLINE]

PARASITIC BRAIN INFECTION, ENDOCANNABINOIDS, AND SCHIZOPHRENIA

 
Med Hypotheses. 2009 Feb;72(2):220-2. Epub 2008 Nov 7.

Parasitic brain infection, endocannabinoids, and schizophrenia.
Melamede R.
Biology Department, University of Colorado at Colorado, Springs, Colorado Springs, CO 80918, USA. rmelamed@uccs.edu

Cannabis use has often been associated with various forms of psychosis. Today it is well established that everyone produces marijuana-like compounds known as endocannabinoids. The endocannabinoid system is a homeostatic regulator of all body systems including the nervous system. As a result, imbalances in the endocannabinoid system have been considered as possible causes of various forms of mental illness and abnormal behavior. In this paper, a novel hypothesis is presented that suggests that an as yet undefined subset of schizophrenia is caused by an excess of endocannabinoids that are produced to protect the brain in response to infections by agents such as Toxoplasma gondii.
 
PMID: 18995970 [PubMed – indexed for MEDLINE]

THE SCHIZOPHRENIA AND TOXOPLASMA GONDII CONNECTION

 
Adv Ther. 2008 Jul;25(7):703-9.

The schizophrenia and Toxoplasma gondii connection: infectious, immune or both?
Tamer GS, Dundar D, Yalug I, Caliskan S, Yazar S, Aker A.

Kocaeli University, Medical Faculty, Department of Clinical Microbiology, Kocaeli, Turkey. guldensonmez@hotmail.com

INTRODUCTION: Recent research has suggested a possible link between toxoplasmic agents and schizophrenia. We aimed to assess this by measuring Toxoplasma gondii-associated antibodies in schizophrenia patients and controls

METHODS: We used a commercially available enzyme-linked immunosorbent assay (ELISA) kit to measure the level of immunoglobulin G (IgG) and IgM antibodies in serum samples from schizophrenia patients (n=40) and from a group of non-schizophrenic control subjects (n=37)

RESULTS: Among schizophrenic patients, 16 (40%) showed IgG seropositivity and two (5%) showed IgM seropositivity. Among the control group, five (13.5%) were found have IgG seropositivity and one (2.7%) showed IgM seropositivity. In our study we found that IgG T gondii antibodies were significantly higher in schizophrenia patients compared with controls

CONCLUSIONS: This study supports the theory that toxoplasmic agents may have a role in the aetiology of schizophrenia.

PMID: 18563312 [PubMed – indexed for MEDLINE]

INFECTIOUS AGENTS AND RISK OF SCHIZOPHRENIA AMONG U.S. MILITARY PERSONNEL

 
Am J Psychiatry. 2008 Jan;165(1):99-106. Epub 2007 Dec 17.

Selected infectious agents and risk of schizophrenia among U.S. military personnel.

Niebuhr DW, Millikan AM, Cowan DN, Yolken R, Li Y, Weber NS.

Department of Epidemiology, Division of Preventive Medicine, Walter Reed Army Institute of Research, 503 Robert Grant Ave., Silver Spring, MD 20901. David.Niebuhr@us.army.mil.

OBJECTIVE: A number of studies have reported associations between Toxoplasma gondii (T. gondii) infection and the risk of schizophrenia. Most existing studies have used small populations and postdiagnosis specimens. As part of a larger research program, the authors conducted a hypothesis-generating case control study of T. gondii antibodies among individuals discharged from the U.S. military with a diagnosis of schizophrenia and serum specimens available from both before and after diagnosis.
 
METHOD: The patients (N=180) were military members who had been hospitalized and discharged from military service with a diagnosis of schizophrenia. Healthy comparison subjects (3:1 matched on several factors) were members of the military who were not discharged. The U.S. military routinely collects and stores serum specimens of military service members. The authors used microplate-enzyme immunoassay to measure immunoglobulin G (IgG) antibody levels to T. gondii, six herpes viruses, and influenza A and B viruses and immunoglobulin M (IgM) antibody levels to T. gondii in pre- and postdiagnosis serum specimens.
 
RESULTS: A significant positive association between the T. gondii IgG antibody and schizophrenia was found; the overall hazard ratio was 1.24. The association between IgG and schizophrenia varied by the time between the serum specimen collection and onset of illness.
 
CONCLUSION: The authors found significant associations between increased levels of scaled T. gondii IgG antibodies and schizophrenia for antibodies measured both prior to and after diagnosis.
 
PMID: 18086751 [PubMed – indexed for MEDLINE]

PSYCHOTIC MANIA IN G6PD SUBJECTS

 
Ann Gen Hosp Psychiatry. 2003 Jun 13;2(1):6.
 
 
Psychotic mania in glucose-6-phosphate-dehydrogenase-deficient subjects.
Bocchetta A.
Bernard B, Brodie Department of Neurosciences, University of Cagliari, Italy. bocchett@unica.it
 
BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency has been associated with acute psychosis, catatonic schizophrenia, and bipolar disorders by previous inconclusive reports. A particularly disproportionate rate of enzyme deficiency was found in manic schizoaffective patients from 662 lithium patients surveyed in Sardinia. The purpose of this study was to describe clinical characteristics which may be potentially associated with G6PD deficiency.
 
 
METHODS: Characteristics of episodes, course of illness, family pattern of illness, laboratory tests, and treatment response of 29 G6PD-deficient subjects with a Research Diagnostic Criteria diagnosis of manic schizoaffective disorder were abstracted from available records.
 
RESULTS: The most peculiar pattern was that of acute recurrent psychotic manic episodes, mostly characterized by loosening of associations, agitation, catatonic symptoms, and/or transient confusion, concurrent hyperbilirubinemia, positive psychiatric family history, and partial response to long-term lithium treatment.
 
 
CONCLUSIONS: A relationship between psychiatric disorder and G6PD deficiency is to be searched in the bipolar spectrum, particularly among patients with a history of acute episodes with psychotic and/or catatonic symptoms or with transient confusion.
 
PMID: 12844366 [PubMed – as supplied by publisher]

PROMINENT PSYCHIATRIC SYMPTOMS IN ANTI-NMDAR ENCEPHALITIS

 
Eur J Clin Microbiol Infect Dis. 2009 Dec;28(12):1421-9. Epub 2009 Aug 29.
 
Anti-NMDA receptor encephalitis: report of ten cases and comparison with viral encephalitis.
Department of Psychiatry, University of California San Francisco, Fresno, CA, USA. ms2gable@yahoo.com
 
The California Encephalitis Project (CEP), established in 1998 to explore encephalitic etiologies, has identified patients with N-methyl-D-aspartate receptor (NMDAR) antibodies, the likely etiology of their encephalitis. This study compares the presentation of such patients to those with viral encephalitis, so that infectious disease clinicians may identify individuals with this treatable disorder. Patients were physician-referred, and standardized forms were used to gather demographic, clinical, and laboratory data. Features of anti-NMDAR+ patients were compared with the viral encephalitides of enteroviral (EV), rabies, and herpes simplex-1 (HSV-1) origins. Sixteen cases with confirmed viral etiologies were all negative on NMDAR antibody testing. Ten anti-NMDAR+ patients were profiled with a median age of 18.5 years (range 11-31 years). None were Caucasian. They had a characteristic progression with prominent psychiatric symptoms, autonomic instability, significant neurologic abnormalities, and seizures. Two had a teratoma, and, of the remaining eight, four had serologic evidence of acute Mycoplasma infection. The clinical and imaging features of anti-NMDAR+ patients served to differentiate this autoimmune disorder from HSV-1, EV, and rabies. Unlike classic paraneoplastic encephalitis, anti-NMDAR encephalitis affects younger patients and is often treatable. The association of NMDAR antibodies in patients with possible Mycoplasma pneumoniae infection warrants further study.
 
PMID: 19718525 [PubMed – in process]