Toxoplasma gondii and Schizophrenia

E. Fuller Torrey, Robert H. Yolken

Disclosures

Emerging Infectious Diseases. 2003;9(11) 

In This Article

Abstract and Introduction

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]

Toxoplasma organisms have also been shown to impair learning and memory in mice[5] and to produce behavioral changes in both mice and rats. Of special interest are studies showing that Toxoplasma-infected rats become less neophobic, leading to the diminution of their natural aversion to the odor of cats.[6] These behavioral changes increase the chances that the rat will be eaten by a cat, thus enabling Toxoplasma to complete its life cycle, an example of evolutionarily driven manipulation of host behavior by the parasite.

In humans, Toxoplasma is an important cause of abortions and stillbirths after primary infection in pregnant women. The organism can also cross the placenta and infect the fetus. The symptoms of congenital toxoplasmosis include abnormal changes in head size (hydrocephaly or microcephaly), intracranial calcifications, deafness, seizures, cerebral palsy, damage to the retina, and mental retardation. Some sequelae of congenital toxoplasmosis are not apparent at birth and may not become apparent until the second or third decade of life. Hydrocephalus,[7] increased ventricular size,[8] and cognitive impairment[9] have also been noted in some persons with schizophrenia and other forms of psychosis.

Some cases of acute toxoplasmosis in adults are associated with psychiatric symptoms such as delusions and hallucinations. A review of 114 cases of acquired toxoplasmosis noted that "psychiatric disturbances were very frequent" in 24 of the case-patients.[10] Case reports describe a 22-year-old woman who exhibited paranoid and bizarre delusions ("she said she had no veins in her arms and legs"), disorganized speech, and flattened affect; a 32-year-old woman who had auditory and visual hallucinations; and a 34-year-old woman who experienced auditory hallucinations and a thought disorder.[11] Schizophrenia was first diagnosed in all three patients, but later neurologic symptoms developed, which led to the correct diagnosis of Toxoplasma encephalitis.

Psychiatric manifestations of T. gondii are also prominent in immunocompromised persons with AIDS in whom latent infections have become reactivated. Reviews of such AIDS cases with toxoplasmosis have indicated that altered mental status may occur in as many as 60% of patients and that the symptoms may include delusions, auditory hallucinations, and thought disorders.[12]

Additional studies have documented that persons with serologic evidence of Toxoplasma infection have evidence of psychiatric changes in the absence of a history of clinically apparent Toxoplasma infection. Studies in which personality questionnaires have been administered to healthy adults have indicated that serum antibodies to T. gondii are associated with alterations in behavior and psychomotor skills.[13] Seropositivity to Toxoplasma has also been associated with "lack of energy or tiredness" in schoolchildren.[14] In view of these findings, we decided to carry out serologic and other studies and to survey the literature for possible additional links between Toxoplasma infection and schizophrenia.

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