Letter to the Editor

Increased prevalence of Toxoplasma gondii seropositivity in patients with treatment-resistant schizophrenia

Toxoplasmosis has been previously associated with an increased risk of having schizophrenia in several epidemiological studies. The aim of this prospective study was to examine for the first time a possible association between positive serology to Toxoplasma gondii (T. gondii) and schizophrenia in the Algerian population. Seventy patients affected by schizophrenia according to DSM-5 criteria and seventy healthy controls were enrolled in the study. We found a significant association between schizophrenia and the infection status with a seroprevalence of 70% in patients with schizophrenia compared to 52.9% in controls and a calculated odds ratio of 2.081. In addition, while T. gondii seroprevalence increases significantly with age in controls, this association was not observed in patients with schizophrenia, which display a high percentage of seropositive subjects under 38 years of age, suggesting that T. gondii infection may promote the onset of schizophrenia. Moreover, our analysis also revealed that patients with schizophrenia had significantly lower levels of serum immunoglobulins G (IgG) to T. gondii compared to controls. Thus, this study adds to previous research questioning the asymptomatic aspect of chronic toxoplasmosis and the etiology of schizophrenia.

Latent Toxoplasma infection has been associated with widespread brain immune activation, increased blood brain barrier permeability, neural disruption, increased dopamine release in dopaminergic neurons, with NMDA activation and with schizophrenia (SZ) onset risk. Toxoplasma has been suggested to be a source of chronic low-grade inflammation and this inflammation has been associated with cognitive impairment in SZ. The objective of the present study were (i) to determine if latent Toxoplasma infection was associated with specific clinical features in stabilized SZ subjects, with cognitive impairment and with increased low-grade peripheral inflammation and (ii) to determine if Treatments with Anti-Toxoplasmic Activity (TATA) were associated with improved outcomes in subjects with latent Toxoplasma infection.

A comprehensive 2 daylong clinical and neuropsychological battery was administered in 250 SZ subjects included between 2015 and 2017 in the national FondaMental Expert Center (FACE-SZ) Cohort. Solid phase-enzyme microplate immunoassay methods were used to measure IgG class of antibodies to T. gondii in blood sample. Latent Toxoplasma infection was defined by T. gondii IgG ratio ≥0.8, equivalent to ≥10 international units. Chronic peripheral inflammation was defined by highly sensitive C reactive protein blood level ≥ 3 mg/L.

Latent Toxoplasma infection has been found in 184 (73.6%) of this national multicentric sample. In the multivariate analyses, latent Toxoplasma infection has been significantly associated with higher PANSS negative (aOR = 1.1 [1.1–1.1], p = 0.04) and excitement subscores (aOR = 1.3 [1.1–1.6], p = 0.01), with two specific symptoms (i.e., reference delusion (aOR = 3.6 [1.2–10.6] p = 0.01) and alogia (aOR = 16.7 [2.0–134.7], p = 0.008)) and with chronic low-grade peripheral inflammation (27.2% vs. 7.6%, aOR = 3.8 [1.4–10.3], p = 0.004). Extrapyramidal symptoms remained significantly associated with latent Toxoplasma infection. On the opposite, no significant association of latent Toxoplasma infection with age, gender, age at SZ onset, suicide behavior or cognitive deficits has been found in these models (all p > 0.05). TATA were associated with lower depressive symptoms (aOR = 0.8[0.7–0.9], p = 0.01), and with lower rates of chronic peripheral inflammation (20.9% vs. 48.6%, aOR = 3.5 [1.5–7.9], p = 0.003) but not with higher cognitive scores (p > 0.05).

The present findings suggest that Toxoplasma is almost 3 times more frequent in SZ population compared to general population in France. The potential cerebral underpinnings of the association of latent Toxoplasma infection and the above-mentioned outcomes have been discussed. Future studies should confirm that TATA may be effective to reduce Toxoplasma-associated depressive symptoms and low-grade peripheral inflammation.