title: 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 1.1million 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.
authors.affiliation: Atlanta Veterans Affairs Medical Center, 1670 Clairmont Rd, Decatur, GA 30033, United States; Department of Epidemiology, Rollins School of Public Health, Emory University, 1518 Clifton Rd., Atlanta, GA 30322, United States.
authors.forename: Nick M
authors.initials: NM
authors.lastname: Massa
authors.affiliation: Atlanta Veterans Affairs Medical Center, 1670 Clairmont Rd, Decatur, GA 30033, United States; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 201 Dowman Drive, Atlanta, GA 30322, United States.
authors.forename: Erica
authors.initials: E
authors.lastname: Duncan
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 201 Dowman Drive, Atlanta, GA 30322, United States.
authors.forename: Tanja
authors.initials: T
authors.lastname: Jovanovic
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 201 Dowman Drive, Atlanta, GA 30322, United States.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Kerley
authors.affiliation: Department of Epidemiology, Rollins School of Public Health, Emory University, 1518 Clifton Rd., Atlanta, GA 30322, United States.
authors.forename: Lei
authors.initials: L
authors.lastname: Weng
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 201 Dowman Drive, Atlanta, GA 30322, United States.
authors.forename: Lauren
authors.initials: L
authors.lastname: Gensler
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 201 Dowman Drive, Atlanta, GA 30322, United States.
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Lee
authors.affiliation: Atlanta Veterans Affairs Medical Center, 1670 Clairmont Rd, Decatur, GA 30033, United States; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 201 Dowman Drive, Atlanta, GA 30322, United States.
authors.forename: Seth
authors.initials: S
authors.lastname: Norrholm
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 201 Dowman Drive, Atlanta, GA 30322, United States.
authors.forename: Abigail
authors.initials: A
authors.lastname: Powers
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 201 Dowman Drive, Atlanta, GA 30322, United States.
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Almli
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 201 Dowman Drive, Atlanta, GA 30322, United States.
authors.forename: Charles F
authors.initials: CF
authors.lastname: Gillespie
authors.affiliation: Department of Psychiatry, Harvard School of Medicine, 25 Shattuck St, Boston, MA 02115, United States.
authors.forename: Kerry
authors.initials: K
authors.lastname: Ressler
authors.affiliation: Department of Epidemiology, Rollins School of Public Health, Emory University, 1518 Clifton Rd., Atlanta, GA 30322, United States. Electronic address: bpearce@emory.edu.
authors.forename: Bradley D
authors.initials: BD
authors.lastname: Pearce
mesh_terms: D000161:Acoustic Stimulation; D000328:Adult; D001741:Black or African American; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D013216:Reflex, Startle / Q000276:immunology*; D012931:Social Environment; D014122:Toxoplasma / Q000276:immunology*; D014123:Toxoplasmosis / Q000276:immunology*; D014505:Urban Population
keywords: Acoustic startle response; Infection; Mental health; PTSD; Schizophrenia; Substance use disorder; Toxoplasma gondii