Schizophrenia Bulletin Advance Access published online on June 2, 2009
Schizophrenia Bulletin, doi:10.1093/schbul/sbp052
Coronavirus Immunoreactivity in Individuals With a Recent Onset of Psychotic Symptoms
2 Stanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Blalock 1105, Baltimore, MD 21287-4933
3 Stanley Research Center, Sheppard Pratt Health System, Baltimore, MD
4 Department of Veterinary Medicine, University of Maryland, College Park, MD
1 To whom correspondence should be addressed; tel: 410-614-3918, fax: 410-955-3723, e-mail: eseverance{at}jhmi.edu.
Prenatal influenza exposure increases the risk for schizophrenia and brings to question how other respiratory viruses may contribute to neuropsychiatric disease etiopathology. Human coronaviruses cause respiratory infections that range in seriousness from common colds to severe acute respiratory syndrome. Like influenza, coronaviruses can be neurotropic. To test for associations between coronaviruses and serious mental disorders, we utilized a recently developed assay and measured immunoglobulin G (IgG) response against 4 human coronavirus strains (229E, HKU1, NL63, and OC43) in 106 patients with a recent onset of psychotic symptoms and 196 nonpsychiatric controls. We expressed results quantitatively as antibody levels and qualitatively as seroprevalence relative to a defined seropositivity cutoff value. Patient IgG levels were higher than controls for HKU1, NL63, and OC43, with HKU1 and NL63 both showing highly significant patient-to-control differences (HKU1, P 
.002; NL63, P .00001). All 4 coronaviruses were more seroprevalent in patients vs controls, with greatest intergroup differences observed for HKU1 (93% vs 77%, P .0001). HKU1 and NL63 associations with the patient group were further supported by multivariate analyses that controlled for age, gender, race, socioeconomic status, and smoking status (HKU1, odds ratio [OR] = 1.32, 95% confidence interval [CI] = 1.03–1.67, P .027; NL63, OR = 2.42, 95% CI = 1.25–4.66, P .008). Among patients, NL63 was associated with schizophrenia-spectrum (OR = 3.10, 95% CI = 1.27–7.58, P .013) but not mood disorders. HKU1 and NL63 coronavirus exposures may represent comorbid risk factors in neuropsychiatric disease. Future studies should explore links between the timing of coronavirus infections and subsequent development of schizophrenia and other disorders with psychotic symptoms.
Keywords: schizophrenia / infection / immunology / pathogen / bipolar disorder / virus