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Persistent infection with neurotropic herpes viruses and cognitive impairment

Published online by Cambridge University Press:  14 September 2012

A. M. M. Watson ,
K. M. Prasad ,
L. Klei ,
J. A. Wood ,
R. H. Yolken ,
R. C. Gur ,
L. D. Bradford ,
M. E. Calkins ,
J. Richard  and
N. Edwards
...Show all authors
A. M. M. Watson
Affiliation:
Departments of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, Pittsburgh, PA, USA
K. M. Prasad
Affiliation:
Departments of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, Pittsburgh, PA, USA
L. Klei
Affiliation:
Departments of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, Pittsburgh, PA, USA
J. A. Wood
Affiliation:
Departments of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, Pittsburgh, PA, USA
R. H. Yolken
Affiliation:
Stanley Division of Developmental Neurovirology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
R. C. Gur
Affiliation:
Department of Psychiatry, Neuropsychiatry Section, University of Pennsylvania, Philadelphia, PA, USA Philadelphia Veteran's Affairs Medical Center, Philadelphia, PA, USA
L. D. Bradford
Affiliation:
Department of Psychiatry, Morehouse School of Medicine, Atlanta, GA, USA
M. E. Calkins
Affiliation:
Department of Psychiatry, Neuropsychiatry Section, University of Pennsylvania, Philadelphia, PA, USA
J. Richard
Affiliation:
Department of Psychiatry, Neuropsychiatry Section, University of Pennsylvania, Philadelphia, PA, USA
N. Edwards
Affiliation:
Department of Psychiatry, University of Tennessee, College of Medicine, Memphis, TN, USA
R. M. Savage
Affiliation:
Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, AL, USA
T. B. Allen
Affiliation:
Duke University Medical Center, John Umstead Hospital, Butner, NC, USA
J. Kwentus
Affiliation:
Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, USA
J. P. McEvoy
Affiliation:
Duke University Medical Center, John Umstead Hospital, Butner, NC, USA
A. B. Santos
Affiliation:
Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, USA
H. W. Wiener
Affiliation:
Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA
R. C. P. Go
Affiliation:
Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA
R. T. Perry
Affiliation:
Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA
H. A. Nasrallah
Affiliation:
Departments of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA
R. E. Gur
Affiliation:
Department of Psychiatry, Neuropsychiatry Section, University of Pennsylvania, Philadelphia, PA, USA
B. Devlin
Affiliation:
Departments of Human Genetics, University of Pittsburgh School of Medicine and Graduate School of Public Health, Western Psychiatric Institute and Clinic, Pittsburgh, PA, USA
V. L. Nimgaonkar*
Affiliation:
Departments of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, Pittsburgh, PA, USA Departments of Human Genetics, University of Pittsburgh School of Medicine and Graduate School of Public Health, Western Psychiatric Institute and Clinic, Pittsburgh, PA, USA
*
*Address for correspondence: V. L. Nimgaonkar, M.D., Ph.D., TDH, Room 441, 3811 O'Hara St., Pittsburgh, PA 15213, USA. (Email: nimga@pitt.edu)
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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.

Keywords

CognitioncytomegalovirusHSV-1HSV-2schizophrenia
Type
Original Articles
Information
Psychological Medicine , Volume 43 , Issue 5 , May 2013 , pp. 1023 - 1031
Copyright
Copyright © Cambridge University Press 2012

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