Parasite Linked to Suicidality in Schizophrenia Patients

Deborah Brauser

May 18, 2012

May 18, 2012 (Philadelphia, Pennsylvania) — Exposure to the Toxoplasma gondii (T gondii) neurotropic parasite may be associated with suicidality in schizophrenia, new research suggests.

In a study of almost 950 adults with schizophrenia, which was presented here at the American Psychiatric Association's (APA's) 2012 Annual Meeting, in those younger than 39 years, there was a significant association between exposure to T gondii and history of suicidal behavior.

In the participants who were aged 39 years or older, there was not a significant link between the 2 factors. This "was particularly noteworthy" because prior research has shown an elevated suicide risk in younger schizophrenia patients compared with older ones, reported the investigators.

"If our findings are replicated in larger studies, this might serve as an impetus for potential novel treatment strategies to prevent suicide in general, and in schizophrenia patients in particular," lead author Olaoluwa Okusaga, MD, from the Mood and Anxiety Program in the Department of Psychiatry at the University of Maryland School of Medicine in Baltimore, told meeting attendees.

Dr. Olaoluwa Okusaga

"Hypothetical future treatment options could include T gondii vaccines, antiparasitic agents, and antiinflammatory and cytokine blocking agents," said Dr. Okusaga.

He added that T gondii was not associated with illness severity.

"With the current shift toward personalized medical care, T gondii serology might become a candidate biomarker for...patients prone to attempting suicide, especially when interaction with vulnerability genes is taken into consideration."

T gondii Infection Common

According to Dr. Okusaga, there are 35,000 completed suicides a year in the United States and a million suicide deaths a year globally.

"This means 1 death every 40 seconds," said Dr. Okusaga. "And suicide rates, according to the Wold Health Organization, have actually increased by 60% in the past 45 years."

He noted that the lifetime risk for suicide in all patients with schizophrenia is approximately 4% to 5%, but that that number may be even higher in younger patients. And this risk persists "even when there are clinical improvements."

"Just treating the symptoms of the disorder alone does not necessarily reduce the risk of suicide," he said.

T gondii is an intracellular protozoan parasite that infects up to one third of the world's population.

"Generally, infection is by ingestion or handling of undercooked or raw meat containing tissue cysts. Or it can be contracted by ingesting water or food that has been contaminated by oocysts, which are present in the feces of infected cats," reported Dr. Okusaga, who added that "congenital infection is also possible."

He noted that the first report of an association between T gondii and suicidal behavior "was by our group" in 2009.

As reported by Medscape Medical News, a study published last year in the American Journal of Psychiatry of more than 45,000 Danish women who had recently given birth found that those with high levels of T gondii–specific lgG antibodies were almost twice as likely to develop subsequent schizophrenia spectrum disorders as the women with low levels of the antibodies.

However, to Dr. Okusaga's knowledge, the association between T gondii with suicidal behavior in primary psychiatric illnesses had not been examined before.

For this study, 950 patients (63% men, 100% white) with schizophrenia were enrolled at centers in Munich, Germany. Immunoassay methods were used to measure IgG plasma antibodies to T gondii, gliadin, herpes simplex virus type 1 (HSV-1), and cytomegalovirus (CMV).

Information on history of suicide attempt was collected in clinical interviews, along with data on duration of illness, dosages of antipsychotic medications, body mass index, and symptom severity on the Positive and Negative Syndrome Scale (PNSS).

The researchers also assessed possible association between T gondii seropositivity or serointensity with history of suicidality.

Mechanism Unclear

Results showed that 351 of the participants had attempted suicide. No association was found between either T gondii seropositivity or serointensity and total or individual scores on PANSS.

T gondii serointensity was significantly associated with past suicidal behavior in the participants younger than the population's median age of 38 years (adjusted odds ratio [OR], 1.23; 95% confidence interval [CI], 1.04 - 1.47; P = .02), as was T gondii seropositivity (adjusted OR, 1.57; 95% CI, 1.03 - 2.38; P = .03).

There were no significant relationships found in those who were aged 38 years or older. In addition, there were no significant associations found between history of suicidality and CMV, HSV-1, or gliadin in any age group.

"The fact that we didn't find these associations point to the less likelihood that our main finding was a nonspecific consequence of a general immune activation in patients with history of suicidal behavior," said Dr. Okusaga.

"What is unclear right now from the data we have is whether it's the microorganism itself that is likely the causal factor or if it's just the immune response to the organism," he added.

Several possible mechanisms he listed for the association include the possibility that T gondii could be a noncausal marker or a "marker of a suicide diathesis, which may include elements of impulsivity and decreases self-care"; or there could be alterations of dopaminergic neurotransmission, intermittent reactivation of latent infection, or stimulated production of high levels of proinflammatory cytokines.

Unusual Area of Research

"This is an interesting article in a somewhat unusual area of research," Jeffrey Lieberman, MD, professor and chair of psychiatry at Columbia University College of Physicians and Surgeons and psychiatrist-in-chief of the New York–Presbyterian Hospital at Columbia University Medical Center in New York City, told Medscape Medical News.

Dr. Jeffrey Lieberman

"The etiology of schizophrenia at this point is still a mystery, although there's a lot of evidence implicating a variety of things, from genes to neurotransmitters to possible immune or infectious etiologies," said Dr. Lieberman.

"Particularly recently, there has been increasing interest in the potential role of toxoplasmosis as the microorganism that may induce brain changes that lead to schizophrenia."

Dr. Lieberman, who was not involved with the current study, is also the president-elect of the APA. He noted that although past research has also suggested "a link between toxo and suicide," he is unsure of its underlying neurobiological rationale or mechanism.

"In this particular study, they found an association between suicidal ideation and behavior with toxo titers in people with schizophrenia. So this is another piece of evidence that adds to the interest in this infectious pathogen etiology to mental illness and the added complication of suicide."

However, he notes that the results are in no way definitive. "At this point, it's just an association that's been demonstrated. But it's not clear if it's really relevant to the cause or if it's coincidental, ancillary, or epiphenomenal."

"Nonetheless, this study broadens the relevance of this potential pathogenic mechanism," said Dr. Lieberman. "For psychiatry, and for the study of higher function of the brain, there's never been a better time. Our knowledge base is increasing rapidly."

The study was funded by the American Foundation for Suicide Prevention. Dr. Okusaga and Dr. Lieberman have disclosed no relevant financial relationships.

The American Psychiatric Association's 2012 Annual Meeting. Abstract SCR11-2. Presented May 6, 2012. Initial findings were reported in the September issue of Biological Psychiatry.

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