Toxoplasma gondii antibody titers and history of suicide attempts in patients with schizophrenia

Abstract

Toxoplasma gondii (T. gondii) a widespread neurotropic parasite, has been previously associated with schizophrenia and more recently with suicidal behavior. However, no previous study has examined the association of T. gondii with suicidal behavior in schizophrenia patients. 950 individuals diagnosed with schizophrenia by SCID were recruited from the Munich area of Germany. Solid-enzyme immunoassay methods were used to measure IgG plasma antibodies to T. gondii, other neurotropic pathogens and gliadin. Logistic regression models were developed to analyze the association of T. gondii seropositivity or serointensity with history of suicidal behavior. In those younger than the median age of the sample, 38, T. gondii serointensity was associated with history of suicidal behavior (p = 0.02), while in the older patients the relationship was not significant (p = 0.21). Seropositivity was also associated with history of suicide attempt in younger patients, odds ratio 1.59 (95% CI 1.06 to 2.40), p = 0.03. Seropositivity for CMV (p = 0.22), HSV-1 (p = 0.36) and gliadin (p = 0.92) was not related to history of suicide attempt in the entire sample or any age subgroup. T. gondii serology might become, with interaction with vulnerability genes, a candidate biomarker for a subgroup of schizophrenia patients prone to attempting suicide.

Introduction

Suicide is a preventable public health problem accounting for 34,598 deaths (eleventh leading cause of death) in the US during 2007 (Centers for Disease Control and Prevention). Suicide is almost always an outcome of mental illness and individuals suffering from a mental illness are more at risk of committing suicide compared to the general population (Hawton and van Heeringen, 2009). Schizophrenia is an illness with high lifetime suicide risk, estimated to be 4–5% (Inskip et al., 1998, Palmer et al., 2005). There is also evidence that the risk of suicide in schizophrenia is higher in younger patients, though the risk (relative to the general population) remains high throughout the illness (Osborn et al., 2008). Adequate control of symptoms alone does not appear to reduce suicide risk in patients with schizophrenia (Shrivastava et al., 2010) and this highlights the need for improvements in clinical and biological predictors of suicidal behavior in these patients.

Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan parasite that infects up to a third of the world's population (Montoya and Liesenfeld, 2004). In the U.S., 10.8% of persons aged 6–49 are seropositive for the parasite (Jones et al., 2007, Dubey and Jones, 2008). T. gondii primary infection is usually asymptomatic in most immunocompetent individuals. Humans commonly become infected by ingestion or handling of undercooked or raw meat containing tissue cysts or ingestion of water or food contaminated by oocysts excreted in the feces of infected cats (the definitive host of the parasite). T. gondii has been linked to schizophrenia and a meta-analysis has demonstrated a higher prevalence of T. gondii antibodies in patients with schizophrenia compared to controls (Torrey et al., 2007). T. gondii has the ability to induce high levels of dopamine in experimental animals and increased dopamine in the mesolimbic areas of the brain has been widely accepted to play a role in the pathogenesis of some symptoms of schizophrenia. In addition, antipsychotic medications used to treat schizophrenia are known to have antiprotozoal activity (Yolken et al., 2009).

The first report of an association between T. gondii and suicidal behavior was made by Arling et al. (2009) in mood disorder patients soon to be replicated by Yagmur et al. (2010). In addition Ling et al. (2011) found the prevalence of T. gondii to be positively associated with national suicide rates for women of postmenopausal age. Therefore, we hypothesized that T. gondii seropositivity and serointensity will be associated with history of suicide attempts in patients with schizophrenia.