title: Persistent infection with neurotropic herpes viruses and cognitive impairment.
abstract: BACKGROUND
  Herpes virus infections can cause cognitive impairment during and after acute encephalitis. Although chronic, latent/persistent infection is considered to be relatively benign, some studies have documented cognitive impairment in exposed persons that is untraceable to encephalitis. These studies were conducted among schizophrenia (SZ) patients or older community dwellers, among whom it is difficult to control for the effects of co-morbid illness and medications. To determine whether the associations can be generalized to other groups, we examined a large sample of younger control individuals, SZ patients and their non-psychotic relatives (n=1852). Method Using multivariate models, cognitive performance was evaluated in relation to exposures to herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2) and cytomegalovirus (CMV), controlling for familial and diagnostic status and sociodemographic variables, including occupation and educational status. Composite cognitive measures were derived from nine cognitive domains using principal components of heritability (PCH). Exposure was indexed by antibodies to viral antigens.
  
  
  RESULTS
  PCH1, the most heritable component of cognitive performance, declines with exposure to CMV or HSV-1 regardless of case/relative/control group status (p = 1.09 × 10-5 and 0.01 respectively), with stronger association with exposure to multiple herpes viruses (β = -0.25, p = 7.28 × 10-10). There were no significant interactions between exposure and group status.
  
  
  CONCLUSIONS
  Latent/persistent herpes virus infections can be associated with cognitive impairments regardless of other health status.
authors.affiliation: Departments of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, Pittsburgh, PA, USA.
authors.forename: A M M
authors.initials: AM
authors.lastname: Watson
authors.forename: K M
authors.initials: KM
authors.lastname: Prasad
authors.forename: L
authors.initials: L
authors.lastname: Klei
authors.forename: J A
authors.initials: JA
authors.lastname: Wood
authors.forename: R H
authors.initials: RH
authors.lastname: Yolken
authors.forename: R C
authors.initials: RC
authors.lastname: Gur
authors.forename: L D
authors.initials: LD
authors.lastname: Bradford
authors.forename: M E
authors.initials: ME
authors.lastname: Calkins
authors.forename: J
authors.initials: J
authors.lastname: Richard
authors.forename: N
authors.initials: N
authors.lastname: Edwards
authors.forename: R M
authors.initials: RM
authors.lastname: Savage
authors.forename: T B
authors.initials: TB
authors.lastname: Allen
authors.forename: J
authors.initials: J
authors.lastname: Kwentus
authors.forename: J P
authors.initials: JP
authors.lastname: McEvoy
authors.forename: A B
authors.initials: AB
authors.lastname: Santos
authors.forename: H W
authors.initials: HW
authors.lastname: Wiener
authors.forename: R C P
authors.initials: RC
authors.lastname: Go
authors.forename: R T
authors.initials: RT
authors.lastname: Perry
authors.forename: H A
authors.initials: HA
authors.lastname: Nasrallah
authors.forename: R E
authors.initials: RE
authors.lastname: Gur
authors.forename: B
authors.initials: B
authors.lastname: Devlin
authors.forename: V L
authors.initials: VL
authors.lastname: Nimgaonkar
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics / Q000523:psychology; D000914:Antibodies, Viral / Q000097:blood; D001921:Brain / Q000821:virology; D016022:Case-Control Studies; D002908:Chronic Disease; D003072:Cognition Disorders / Q000453:epidemiology* / Q000235:genetics / Q000821:virology; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000097:blood / Q000453:epidemiology*; D004522:Educational Status; D004651:Employment; D005260:Female; D020022:Genetic Predisposition to Disease; D006561:Herpes Simplex / Q000097:blood / Q000453:epidemiology*; D006801:Humans; D008297:Male; D015233:Models, Statistical; D015999:Multivariate Analysis; D009483:Neuropsychological Tests / Q000706:statistics & numerical data*; D010641:Phenotype; D025341:Principal Component Analysis; D012559:Schizophrenia / Q000453:epidemiology* / Q000235:genetics / Q000821:virology; D018139:Simplexvirus / Q000276:immunology
chemical_list: D000914:Antibodies, Viral