Relationship between Toxoplasma gondii seropositivity and acoustic startle response in an inner-city population

Abstract

Toxoplasma gondii (TOXO) is a neuroinvasive protozoan parasite that induces the formation of persistent cysts in mammalian brains. It infects approximately 1.1 million people in the United States annually. Latent TOXO infection is implicated in the etiology of psychiatric disorders, especially schizophrenia (Scz), and has been correlated with modestly impaired cognition. The acoustic startle response (ASR) is a reflex seen in all mammals. It is mediated by a simple subcortical circuit, and provides an indicator of neural function. We previously reported the association of TOXO with slowed acoustic startle latency, an index of neural processing speed, in a sample of schizophrenia and healthy control subjects. The alterations in neurobiology with TOXO latent infection may not be specific to schizophrenia. Therefore we examined TOXO in relation to acoustic startle in an urban, predominately African American, population with mixed psychiatric diagnoses, and healthy controls. Physiological and diagnostic data along with blood samples were collected from 364 outpatients treated at an inner-city hospital. TOXO status was determined with an ELISA assay for TOXO-specific IgG. A discrete titer was calculated based on standard cut-points as an indicator of seropositivity, and the TOXO-specific IgG concentration served as serointensity. A series of linear regression models were used to assess the association of TOXO seropositivity and serointensity with ASR magnitude and latency in models adjusting for demographics and psychiatric diagnoses (PTSD, major depression, schizophrenia, psychosis, substance abuse). ASR magnitude was 11.5% higher in TOXO seropositive subjects compared to seronegative individuals (p=0.01). This effect was more pronounced in models with TOXO serointensity that adjusted for sociodemographic covariates (F=7.41, p=.0068; F=10.05, p=0.0017), and remained significant when psychiatric diagnoses were stepped into the models. TOXO showed no association with startle latency (t=0.49, p=0.63) in an unadjusted model, nor was TOXO associated with latency in models that included demographic factors. After stepping in individual psychiatric disorders, we found a significant association of latency with a diagnosis of PTSD (F=5.15, p=0.024), but no other psychiatric diagnoses, such that subjects with PTSD had longer startle latency. The mechanism by which TOXO infection is associated with high startle magnitude is not known, but possible mechanisms include TOXO cyst burden in the brain, parasite recrudescence, or molecular mimicry of a host epitope by TOXO. Future studies will focus on the neurobiology underlying the effects of latent TOXO infection as a potential inroad to the development of novel treatment targets for psychiatric disease.

Is there any association between Toxoplasma gondii infection and depression? A systematic review and meta-analysis

“…According to Fig 2, the lowest and highest ORs are related to the studies performed by Massa et al . [46] and Conejero-Goldberg et al . [22], respectively.…”

“…used a larger sample size with a different set of psychiatric diagnoses. Moreover, race, educational level, and economic status can result in different ORs [46].…”

A Gene-Based Analysis of Acoustic Startle Latency

“…However, a slowing of latency is not unique to schizophrenia. It has been reported in autism ( 32 , 33 ), Huntington’s disease ( 34 ), and post-traumatic stress disorder ( 25 , 35 ). It is unknown how closely the neural underpinnings of slowed latency in schizophrenia may overlap with that of these other disorders.…”

Moderation of the relationship between Toxoplasma gondii seropositivity and trait impulsivity in younger men by the phenylalanine-tyrosine ratio

“…Similarly, other experimental studies also found that dopaminergic neurons containing T. gondii have demonstrated an increased synthesis of dopamine and an elevated presence of homovanillic acid, a dopamine metabolite (Stibbs, 1985; Prandovszky et al, 2011; Martin et al, 2015). A recent study reported a higher acoustic startle response magnitude among T. gondii infected participants (Massa et al, 2017). The authors proposed that the finding might be the outcome of increased dopamine production (Swerdlow et al, 1986; Parlog et al, 2015).…”