Relationship between Toxoplasma gondii Seropositivity and Acoustic Startle Response in an Inner-City Population

• Authors: Nick M. Massa, Emory University; Erica Duncan, Emory University; Tanja Jovanovic, Emory University; Kimberly Kerley, Emory University; Lei Weng, Emory University; Lauren Gensler, Emory University; Samuel S. Lee, Emory University; Seth Davin Norrholm, Emory University; Abigail Powers, Emory University; Lynn Almli, Emory University; Charles Gillespie, Emory University; Kerry Ressler, Emory University; Brad Pearce, Emory University
• Journal Title: Brain, Behavior, and Immunity
• Volume: Volume 61
• Publisher: Elsevier: 12 months | 2017-03-01, Pages 176-183
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1016/j.bbi.2016.11.021
• Subjects: Health Sciences, Public Health; Psychology, Behavioral; Health Sciences, Medicine and Surgery
• Keywords: Science & Technology; Life Sciences & Biomedicine; Immunology; Neurosciences; Neurosciences & Neurology; Acoustic startle response; Toxoplasma gondii; PTSD; Mental health; Infection; Substance use disorder; Schizophrenia; POSTTRAUMATIC-STRESS-DISORDER; LATENT TOXOPLASMOSIS; BIPOLAR DISORDER; UNITED-STATES; RISK-FACTORS; PREPULSE INHIBITION; HUMAN PERSONALITY; FEAR INHIBITION; INFECTION; SCHIZOPHRENIA

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 = 0.0068; 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.