Mothers with IgG antibodies to Toxoplasma gondii at delivery are at risk for later self-harm or suicide, particularly if they have higher titers against the parasite, a Danish study found.

The risk of self-directed violent behavior was increased 1.53-fold (95% CI 1.27 to 1.85, P<0.001) for women who tested positive for the antibody compared with those testing negative, according to Teodor T. Postolache, MD, of the University of Maryland in Baltimore, and colleagues.

For those whose titers exceeded 83, placing them in the 90th percentile, the relative risk rose to 1.91 (95% CI 1.25 to 2.79, P<0.001), the researchers reported online in Archives of General Psychiatry.

Toxoplasma gondii is a common protozoa that, if ingested, can migrate to the brain, where it can remain in a cystic form in glial cells and neurons.

Typical sources of infection include cat litter boxes, undercooked meat that contains parasite cysts, and unwashed vegetables. Areas in the brain favored by the parasite include the amygdala and prefrontal cortex, regions that play prominent roles in the regulation of emotion and behavior, and that show abnormalities in patients with schizophrenia. The researchers had previously identified a link between T. gondii and suicidal behavior, although in their earlier studies the violent event took place before antibody testing for the infection. Therefore, to examine a possible predictive effect for T. gondii infection and self-harm, the researchers identified infected women by testing their infants shortly after birth for the presence of antibodies, which would be maternal in origin. Among 45,271 Danish women who gave birth between 1992 and 1995, 26.8% were seropositive. For the analysis, the women were stratified for a personal or family history of mental illness, which was ascertained by extracting data from the Danish Psychiatric Central Research Register. During the follow-up period, which extended until 2006, there were 488 attempts at self-harm among the cohort, for an incidence rate of 8.20 per 10,000 person-years. The risk among seropositive women with a history of psychiatric illness was 1.25 (95% CI 0.94 to 1.66, P=0.12), while the risk for those without such a history was 1.56 (95% CI 1.21 to 2, P<0.001). "Because many patients with, for example, mood or substance use disorders may not have been treated as inpatients or outpatients in psychiatric clinics, we cannot exclude that some of the effect of T. gondii infection in women without a psychiatric diagnosis is mediated by an elevation of risk for mental disorders," the researchers noted. A total of 517 of the women had already had an episode of self-directed violent behavior at the time of delivery, and among these, the relative risk of another attempt was 1.54 (95% CI 0.98 to 2.39, P=0.06). During 603,876 person-years of follow-up, there were 78 violent attempts at suicide. The relative risk was 1.81 (95% CI 1.13 to 2.84, P=0.01) for seropositive women. Eight of the attempts among seropositive women succeeded, providing a relative risk of completed suicide of 2.05 (95% CI 0.78 to 5.20, P=0.14). The researchers explained that a likely mechanism by which T. gondii could provoke self-harm is through a "neuroimmune path," because the chronic infection is controlled by the immune system, particularly by pro-inflammatory cytokines such as interleukin-6 and tumor necrosis factor-alpha. Elevated levels of these same cytokines have been identified in the peripheral blood and cerebrospinal fluid of individuals who attempted suicide. Recent research also has implicated other alterations in neuromodulators in both the parasitic infections and self-harming behavior, such as through the upregulation of kynurenine pathways in the brain. As to why the risk for self-injury should be higher with increased IgG antibody titers, the researchers suggested that higher titers could reflect more recent infection or reactivation. However, they had no information on IgM titers that could clarify the timing of infection, so this remained a limitation of the study. Another limitation was that, while the data on self-harm were collected prospectively, an infectious causality cannot be assumed. Further shortcomings include the exclusion of men, and the small number of actual violent suicides. Nonetheless, the researchers concluded, "Our results are consistent with the hypothesized association between T. gondii infection and self-directed violence and, in concert with other converging evidence and better understanding of underlying mechanisms, if confirmed in future studies, may lead to new prognostic, prophylactic, and therapeutic approaches to suicide prevention."